|
1
|
Su M, Zhu J, Bai L, Cao Y, Wang S. Exploring manzamine a: a promising anti-lung cancer agent from marine sponge Haliclona sp. Front Pharmacol 2025; 16:1525210. [PMID: 40070571 PMCID: PMC11893592 DOI: 10.3389/fphar.2025.1525210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 02/11/2025] [Indexed: 03/14/2025] Open
Abstract
Manzamine A (MA), a bioactive compound derived from the marine sponge Haliclona sp., shows considerable therapeutic potential, particularly in the treatment of various cancer types. Extracted with acetone and purified through chromatography, MA exhibits a bioavailability of 20.6% when administered orally in rats, underscoring its feasibility for therapeutic use. This compound disrupts key cellular mechanisms essential for cancer progression, including microtubule dynamics and DNA replication enzymes, demonstrating strong anti-proliferative effects against multiple cancer cell lines while sparing normal cells. Additionally, network pharmacology and molecular docking studies reveal MA's interactions with important targets related to lung cancer progression, such as EGFR and SRC, bolstering its potential as a novel anti-lung cancer agent. Pathway analyses further indicate that MA influences critical signaling pathways involved in tumor growth and metastasis. Given the urgent need for effective treatments against drug-resistant cancers and the limited toxicity profile of MA, further exploration of its pharmacological benefits and mechanism could pave the way for new therapeutic strategies in lung cancer.
Collapse
Affiliation(s)
- Min Su
- School of Pharmacy, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Jie Zhu
- Department of Scientific Research Management and Foreign Affairs, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Luyuan Bai
- School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Yu Cao
- Clinical Trials Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Shaohui Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
2
|
Gottumukkala SB, Palanisamy A. Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators. Mamm Genome 2025:10.1007/s00335-025-10110-6. [PMID: 39939487 DOI: 10.1007/s00335-025-10110-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Accepted: 01/29/2025] [Indexed: 02/14/2025]
Abstract
Non-Small Cell lung cancer (NSCLC) is known for its fast progression, metastatic potency, and a leading cause of mortality globally. At diagnosis, approximately 30-40% of NSCLC patients already present with metastasis. Epithelial to mesenchymal transition (EMT) is a developmental program implicated in cancer progression and metastasis. Transforming Growth Factor-β (TGFβ) and its signalling plays a prominent role in orchestrating the process of EMT and cancer metastasis. In present study, a comprehensive molecular interaction map of TGFβ induced EMT in NSCLC was developed through an extensive literature survey. The map encompasses 394 species interconnected through 554 reactions, representing the relationship and complex interplay between TGFβ induced SMAD dependent and independent signalling pathways (PI3K/Akt, Wnt, EGFR, JAK/STAT, p38 MAPK, NOTCH, Hypoxia). The map, built using Cell Designer and compliant with SBGN and SBML standards, was subsequently translated into a logical modelling framework using CaSQ and dynamically analysed with Cell Collective. These analyses illustrated the complex regulatory dynamics, capturing the known experimental outcomes of TGFβ induced EMT in NSCLC including the co-existence of hybrid EM phenotype during transition. Hybrid EM phenotype is known to contribute for the phenotypic plasticity during metastasis. Network-based analysis identified the crucial network level properties and hub regulators, while the transcriptome-based analysis cross validated the prognostic significance and clinical relevance of key regulators. Overall, the map developed and the subsequent analyses offer deeper understanding of the complex regulatory network governing the process of EMT in NSCLC.
Collapse
Affiliation(s)
- Sai Bhavani Gottumukkala
- Department of Biotechnology, National Institute of Technology Warangal, Warangal, Telangana, India
| | - Anbumathi Palanisamy
- Department of Biotechnology, National Institute of Technology Warangal, Warangal, Telangana, India.
| |
Collapse
|
|
3
|
Ma L, Zhang J, Dai Z, Liao P, Guan J, Luo Z. Top 100 most-cited articles on apoptosis of non-small cell lung cancer over the past two decades: a bibliometrics analysis. Front Immunol 2025; 15:1512349. [PMID: 39872524 PMCID: PMC11770037 DOI: 10.3389/fimmu.2024.1512349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 12/09/2024] [Indexed: 01/30/2025] Open
Abstract
Background Recently there has been an increasing number of studies have explored apoptosis mechanisms in lung cancer (LC). However, no researchers have conducted a bibliometric analysis of the most cited articles in this field. Objective To examine the top 100 most influential and cited publications on apoptosis in non-small cell lung cancer (NSCLC) from 2004 to 2023, summarizing research trends and key focus areas. Methods This study utilized the Web of Science Core Database (WOSCC) to research NSCLC apoptosis from 2004 to 2023, using keyword selection and manual screening for article searches. Bibliometrix package of R software 4.3.1 was used to generate distribution statistics for the top ten institutions, journals and authors. Citespace6.2. R6 was used to create the visualization maps for keyword co-occurrence and clustering. VOSviewer1.6.19 was used to conduct cluster analysis of publishing countries (regions), with data exported to SCImago Graphica for geographic visualization and cooperation analysis. VOSviewer1.6.19 was used to produced co-citation maps of institutions, journals, authors, and references. Results From 2004 to 2023, 13316 articles were retrieved, and the top 100 most cited were chosen. These were authored by 934 individuals from 269 institutions across 18 countries and appeared in 45 journals. Citations ranged from 150 to 1,389, with a median of 209.5. The most influential articles appeared in 2005 and 2007 (n=13). The leading countries (regions), institutions, journals and authors were identified as the United States (n=60), Harvard University (n=64), CANCER RESEARCH (n=15), SUN M and YANG JS (n=6). The top five keywords were "expression", "activation", "apoptosis", "pathway" and "gefitinib". This study indicates that enhancing apoptosis through circular RNA regulation and targeting the Nrf2 signaling pathway could become a key research focus in recent years. Conclusion Apoptosis has been the subject of extensive research over many years, particularly in relation to its role in the pathogenesis, diagnosis, and treatment of NSCLC. This study aims to identify highly influential articles and forecast emerging research trends, thereby offering insights into novel therapeutic targets and strategies to overcome drug resistance. The findings are intended to serve as a valuable reference for scholars engaged in this field of study.
Collapse
Affiliation(s)
- Leshi Ma
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jing Zhang
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zi Dai
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Pei Liao
- Department of Oncology, Chongqing Hospital, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Chongqing, China
| | - Jieshan Guan
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Oncology, Shenshan Hospital, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Shanwei, China
| | - Zhijie Luo
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| |
Collapse
|
|
4
|
Kadian LK, Verma D, Lohani N, Yadav R, Ranga S, Gulshan G, Pal S, Kumari K, Chauhan SS. Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy. Mol Cell Biochem 2024; 479:3229-3254. [PMID: 38413478 DOI: 10.1007/s11010-024-04933-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 01/05/2024] [Indexed: 02/29/2024]
Abstract
Cancer remains a major global health concern with high mortality rates mainly due to late diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in human cancer, functioning through various mechanisms including as competing endogenous RNAs (ceRNAs) and indirectly regulating miRNA expression. LncRNAs have been found to have both oncogenic and tumor-suppressive roles in cancer, with the former promoting cancer cell proliferation, migration, invasion, and poor prognosis. Recent research has shown that lncRNAs are expressed in various immune cells and are involved in cancer cell immune escape and the modulation of the tumor microenvironment, thus highlighting their potential as targets for cancer immunotherapy. Targeting lncRNAs in cancer or immune cells could enhance the anti-tumor immune response and improve cancer immunotherapy outcomes. However, further research is required to fully understand the functional roles of lncRNAs in cancer and the immune system and their potential as targets for cancer immunotherapy. This review offers a comprehensive examination of the multifaceted roles of lncRNAs in human cancers, with a focus on their potential as targets for cancer immunotherapy. By exploring the intricate mechanisms underlying lncRNA-mediated regulation of cancer cell proliferation, invasion, and immune evasion, we provide insights into the diverse therapeutic applications of these molecules.
Collapse
Affiliation(s)
- Lokesh K Kadian
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India
- Dept of Dermatology, Indiana University School of Medicine, Indianapolis, 46202, USA
| | - Deepika Verma
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Neelam Lohani
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Ritu Yadav
- Dept of Genetics, MD University, Rohtak, 124001, India
| | - Shalu Ranga
- Dept of Genetics, MD University, Rohtak, 124001, India
| | - Gulshan Gulshan
- Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India
| | - Sanghapriya Pal
- Dept of Biochemistry, Maulana Azad Medical College and Associated Hospital, New Delhi, 110002, India
| | - Kiran Kumari
- Dept of Forensic Science, Lovely Professional University, Jalandhar, Punjab, 144411, India
| | - Shyam S Chauhan
- Dept of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.
| |
Collapse
|
|
5
|
Tomecka P, Kunachowicz D, Górczyńska J, Gebuza M, Kuźnicki J, Skinderowicz K, Choromańska A. Factors Determining Epithelial-Mesenchymal Transition in Cancer Progression. Int J Mol Sci 2024; 25:8972. [PMID: 39201656 PMCID: PMC11354349 DOI: 10.3390/ijms25168972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/12/2024] [Accepted: 08/15/2024] [Indexed: 09/02/2024] Open
Abstract
Epithelial-mesenchymal transition (EMT) is a process in which an epithelial cell undergoes multiple modifications, acquiring both morphological and functional characteristics of a mesenchymal cell. This dynamic process is initiated by various inducing signals that activate numerous signaling pathways, leading to the stimulation of transcription factors. EMT plays a significant role in cancer progression, such as metastasis and tumor heterogeneity, as well as in drug resistance. In this article, we studied molecular mechanisms, epigenetic regulation, and cellular plasticity of EMT, as well as microenvironmental factors influencing this process. We included both in vivo and in vitro models in EMT investigation and clinical implications of EMT, such as the use of EMT in curing oncological patients and targeting its use in therapies. Additionally, this review concludes with future directions and challenges in the wide field of EMT.
Collapse
Affiliation(s)
- Paulina Tomecka
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (P.T.); (J.G.); (M.G.); (J.K.); (K.S.)
| | - Dominika Kunachowicz
- Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland;
| | - Julia Górczyńska
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (P.T.); (J.G.); (M.G.); (J.K.); (K.S.)
| | - Michał Gebuza
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (P.T.); (J.G.); (M.G.); (J.K.); (K.S.)
| | - Jacek Kuźnicki
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (P.T.); (J.G.); (M.G.); (J.K.); (K.S.)
| | - Katarzyna Skinderowicz
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; (P.T.); (J.G.); (M.G.); (J.K.); (K.S.)
| | - Anna Choromańska
- Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wroclaw, Poland
| |
Collapse
|
|
6
|
Dong X, Shao C, Xu S, Tu J, Xu W, Chen D, Tang Y. Construction and validation of a prognostic signature based on anoikis-related lncRNAs in lung adenocarcinoma. Aging (Albany NY) 2024; 16:9899-9917. [PMID: 38850527 PMCID: PMC11210241 DOI: 10.18632/aging.205905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 05/02/2024] [Indexed: 06/10/2024]
Abstract
Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is characterized by a high death rate and a poor prospect for survival. Anoikis, which is a kind of programmed cell apoptosis, is an important factor in the advancement of tumors. Nonetheless, the function of anoikis-related lncRNAs (ARLRs) in LUAD is still not well understood. The TCGA database was queried for genomic and clinical information. A prognostic signature for ARLRs was established via the use of coexpression analysis and Cox regression. Validation of the model's accuracy was conducted utilizing K-M curves and receiver operating characteristic (ROC) curves, and the signature was utilized to develop a nomogram. LncRNAs were implicated in the progression of tumors, as determined by functional enrichment analysis. There was an improvement in prognosis, increased immune cell infiltration, and higher immune scores among the low-risk patients. Additionally, we found that the two groups had varied anticancer drug sensitivities, which could help guide treatment. The impact of one ARLR, AC026355.2, on migration and invasion was validated by in vitro experiments in LUAD cells. Herein, a new lncRNA signature associated with anoikis was identified and estimated, potentially serving as a prognostic indicator for LUAD patients.
Collapse
Affiliation(s)
- Xiaoqi Dong
- Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, China
| | - Chuan Shao
- Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, China
| | - Shuguang Xu
- Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, China
| | - Jinjing Tu
- Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, China
| | - Wenjing Xu
- Ningbo University Health Science Center, Ningbo, China
| | - Dahua Chen
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, China
| | - Yaodong Tang
- Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, China
| |
Collapse
|
|
7
|
Lv H, Qian D, Xu S, Fan G, Qian Q, Cha D, Qian X, Zhou G, Lu B. Modulation of long noncoding RNAs by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review. Phytother Res 2024; 38:3240-3267. [PMID: 38739454 DOI: 10.1002/ptr.8202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 03/10/2024] [Accepted: 03/19/2024] [Indexed: 05/16/2024]
Abstract
Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.
Collapse
Affiliation(s)
- Hong Lv
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Dawei Qian
- Department of Thoracic Surgery, Tongling Yi'an District People's Hospital, Tongling, China
| | - Shuhua Xu
- Department of Cardiothoracic Surgery, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, China
| | - Guiqin Fan
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Qiuhong Qian
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Dongsheng Cha
- Department of Thoracic Surgery, Tongling Yi'an District People's Hospital, Tongling, China
| | - Xingjia Qian
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Guoping Zhou
- Department of Cardiothoracic Surgery, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, China
| | - Bing Lu
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| |
Collapse
|
|
8
|
Gilyazova I, Gimalova G, Nizamova A, Galimova E, Ishbulatova E, Pavlov V, Khusnutdinova E. Non-Coding RNAs as Key Regulators in Lung Cancer. Int J Mol Sci 2023; 25:560. [PMID: 38203731 PMCID: PMC10778604 DOI: 10.3390/ijms25010560] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/21/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
For several decades, most lung cancer investigations have focused on the search for mutations in candidate genes; however, in the last decade, due to the fact that most of the human genome is occupied by sequences that do not code for proteins, much attention has been paid to non-coding RNAs (ncRNAs) that perform regulatory functions. In this review, we principally focused on recent studies of the function, regulatory mechanisms, and therapeutic potential of ncRNAs including microRNA (miRNA), long ncRNA (lncRNA), and circular RNA (circRNA) in different types of lung cancer.
Collapse
Affiliation(s)
- Irina Gilyazova
- Institute of Biochemistry and Genetics, Ufa Federal Research Center of Russian Academy of Sciences, 450054 Ufa, Russia
- Institute of Urology and Clinical Oncology, Department of Medical Genetics and Fundamental Medicine, Bashkir State Medical University, 450008 Ufa, Russia
| | - Galiya Gimalova
- Institute of Biochemistry and Genetics, Ufa Federal Research Center of Russian Academy of Sciences, 450054 Ufa, Russia
- Institute of Urology and Clinical Oncology, Department of Medical Genetics and Fundamental Medicine, Bashkir State Medical University, 450008 Ufa, Russia
| | - Aigul Nizamova
- Institute of Biochemistry and Genetics, Ufa Federal Research Center of Russian Academy of Sciences, 450054 Ufa, Russia
| | - Elmira Galimova
- Department of Pathological Physiology, Bashkir State Medical University, 450008 Ufa, Russia
| | - Ekaterina Ishbulatova
- Institute of Urology and Clinical Oncology, Department of Medical Genetics and Fundamental Medicine, Bashkir State Medical University, 450008 Ufa, Russia
| | - Valentin Pavlov
- Institute of Urology and Clinical Oncology, Department of Urology, Bashkir State Medical University, 450008 Ufa, Russia
| | - Elza Khusnutdinova
- Institute of Biochemistry and Genetics, Ufa Federal Research Center of Russian Academy of Sciences, 450054 Ufa, Russia
- Institute of Urology and Clinical Oncology, Department of Medical Genetics and Fundamental Medicine, Bashkir State Medical University, 450008 Ufa, Russia
| |
Collapse
|
|
9
|
Li Y, Tang D, Zhang J, Ou W, Sun X, Yang Q, Wu J. LncRNA SPRY4-IT1 regulates 16HBE cell malignant transformation induced by particulate matter through DUSP6-ERK1/2-Chk1 signaling pathway. CHEMOSPHERE 2023; 344:140358. [PMID: 37797900 DOI: 10.1016/j.chemosphere.2023.140358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 09/16/2023] [Accepted: 10/02/2023] [Indexed: 10/07/2023]
Abstract
Particulate matter (PM), one of the most serious air contaminants, could easily pass through the airway and deposit at the deep alveoli. Thus, it might trigger respiratory diseases like inflammation, asthma and lung cancer on human. Long non-coding RNAs (lncRNAs) are considered as important regulator in promotion and progression of diverse cancers. However, the molecular mechanism of lncRNAs mediating PM-induced lung carcinogenesis remains unclear. In this study, we established a 16HBE malignant transformed cell induced by PM (Cells were treated with 20 μg/ml PM, which named PM-T cells) and explored the roles and mechanisms of lncRNAs in the malignant transformation induced by PM. Compared with 16HBE cells, various biological functions were changed in PM-T cells, such as cell proliferation, migration, cell cycle and apoptosis. LncRNA SPRY4-IT1 was significant down-regulated expression and associated with these biological effects. Our results showed that lncRNA SPRY4-IT1 overexpression reversed these functional changes mentioned above. The further studies indicated that lncRNA SPRY4-IT1 involved in PM-induced cell transformation by modulating Chk1 expression via negative regulation of DUSP6-ERK1/2. In conclusion, our studies suggested that lncRNA SPRY4-IT1 played the role as a tumor suppressor gene and might mediate 16HBE cells malignant transformation induced by PM through regulating DUSP6-ERK1/2-Chk1 signaling pathway.
Collapse
Affiliation(s)
- Yanli Li
- State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, PR China.
| | - Dan Tang
- State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, PR China.
| | - Jian Zhang
- State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, PR China.
| | - Wanting Ou
- State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, PR China.
| | - Xuan Sun
- State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, PR China.
| | - Qiaoyuan Yang
- State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, PR China.
| | - Jianjun Wu
- State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, PR China.
| |
Collapse
|
|
10
|
Gao M, Li Y, Cao P, Liu H, Chen J, Kang S. Exploring the therapeutic potential of targeting polycomb repressive complex 2 in lung cancer. Front Oncol 2023; 13:1216289. [PMID: 37909018 PMCID: PMC10613995 DOI: 10.3389/fonc.2023.1216289] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 10/02/2023] [Indexed: 11/02/2023] Open
Abstract
The pathogenesis of lung cancer (LC) is a multifaceted process that is influenced by a variety of factors. Alongside genetic mutations and environmental influences, there is increasing evidence that epigenetic mechanisms play a significant role in the development and progression of LC. The Polycomb repressive complex 2 (PRC2), composed of EZH1/2, SUZ12, and EED, is an epigenetic silencer that controls the expression of target genes and is crucial for cell identity in multicellular organisms. Abnormal expression of PRC2 has been shown to contribute to the progression of LC through several pathways. Although targeted inhibition of EZH2 has demonstrated potential in delaying the progression of LC and improving chemotherapy sensitivity, the effectiveness of enzymatic inhibitors of PRC2 in LC is limited, and a more comprehensive understanding of PRC2's role is necessary. This paper reviews the core subunits of PRC2 and their interactions, and outlines the mechanisms of aberrant PRC2 expression in cancer and its role in tumor immunity. We also summarize the important role of PRC2 in regulating biological behaviors such as epithelial mesenchymal transition, invasive metastasis, apoptosis, cell cycle regulation, autophagy, and PRC2-mediated resistance to LC chemotherapeutic agents in LC cells. Lastly, we explored the latest breakthroughs in the research and evaluation of medications that target PRC2, as well as the latest findings from clinical studies investigating the efficacy of these drugs in the treatment of various human cancers.
Collapse
Affiliation(s)
- Min Gao
- Department of Thoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
- Inner Mongolia Medical University, First Clinical Medical College, Hohhot, China
| | - Yongwen Li
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Peijun Cao
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Hongyu Liu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Jun Chen
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
- Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Shirong Kang
- Department of Thoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| |
Collapse
|
|
11
|
Hussain MS, Afzal O, Gupta G, Altamimi ASA, Almalki WH, Alzarea SI, Kazmi I, Fuloria NK, Sekar M, Meenakshi DU, Thangavelu L, Sharma A. Long non-coding RNAs in lung cancer: Unraveling the molecular modulators of MAPK signaling. Pathol Res Pract 2023; 249:154738. [PMID: 37595448 DOI: 10.1016/j.prp.2023.154738] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 08/20/2023]
Abstract
Lung cancer (LC) continues to pose a significant global medical burden, necessitating a comprehensive understanding of its molecular foundations to establish effective treatment strategies. The mitogen-activated protein kinase (MAPK) signaling system has been scientifically associated with LC growth; however, the intricate regulatory mechanisms governing this system remain unknown. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of diverse cellular activities, including cancer growth. LncRNAs have been implicated in LC, which can function as oncogenes or tumor suppressors, and their dysregulation has been linked to cancer cell death, metastasis, spread, and proliferation. Due to their involvement in critical pathophysiological processes, lncRNAs are gaining attention as potential candidates for anti-cancer treatments. This article aims to elucidate the regulatory role of lncRNAs in MAPK signaling in LC. We provide a comprehensive review of the key components of the MAPK pathway and their relevance in LC, focusing on aberrant signaling processes associated with disease progression. By examining recent research and experimental findings, this article examines the molecular mechanisms through which lncRNAs influence MAPK signaling in lung cancer, ultimately contributing to tumor development.
Collapse
Affiliation(s)
- Md Sadique Hussain
- School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, 302017 Jaipur, Rajasthan, India
| | - Obaid Afzal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India; School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India
| | | | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | - Mahendran Sekar
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | | | - Lakshmi Thangavelu
- Center for Global Health Research , Saveetha Medical College , Saveetha Institute of Medical and Technical Sciences, Saveetha University, India
| | - Ajay Sharma
- Delhi Pharmaceutical Science and Research University, Pushp Vihar Sector-3, MB Road, New Delhi 110017, India.
| |
Collapse
|
|
12
|
Entezari M, Taheriazam A, Paskeh MDA, Sabouni E, Zandieh MA, Aboutalebi M, Kakavand A, Rezaei S, Hejazi ES, Saebfar H, Salimimoghadam S, Mirzaei S, Hashemi M, Samarghandian S. The pharmacological and biological importance of EZH2 signaling in lung cancer. Biomed Pharmacother 2023; 160:114313. [PMID: 36738498 DOI: 10.1016/j.biopha.2023.114313] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 01/20/2023] [Accepted: 01/26/2023] [Indexed: 02/05/2023] Open
Abstract
Up to 18% of cancer-related deaths worldwide are attributed to lung tumor and global burden of this type of cancer is ascending. Different factors are responsible for development of lung cancer such as smoking, environmental factors and genetic mutations. EZH2 is a vital protein with catalytic activity and belongs to PCR2 family. EZH2 has been implicated in regulating gene expression by binding to promoter of targets. The importance of EZH2 in lung cancer is discussed in current manuscript. Activation of EZH2 significantly elevates the proliferation rate of lung cancer. Furthermore, metastasis and associated molecular mechanisms including EMT undergo activation by EZH2 in enhancing the lung cancer progression. The response of lung cancer to therapy can be significantly diminished due to EZH2 upregulation. Since EZH2 increases tumor progression, anti-cancer agents suppressing its expression reduce malignancy. In spite of significant effort in understanding modulatory function of EZH2 on other pathways, it appears that EZH2 can be also regulated and controlled by other factors that are described in current review. Therefore, translating current findings to clinic can improve treatment and management of lung cancer patients.
Collapse
Affiliation(s)
- Maliheh Entezari
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mahshid Deldar Abad Paskeh
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Eisa Sabouni
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Maryam Aboutalebi
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Amirabbas Kakavand
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Shamin Rezaei
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Elahe Sadat Hejazi
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Hamidreza Saebfar
- European University Association, League of European Research Universities, university of milan, Italy
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Saeed Samarghandian
- Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran.
| |
Collapse
|
|
13
|
Luan H, Yan L, Zhao Y, Ding X, Cao L. Fucoxanthin induces apoptosis and reverses epithelial-mesenchymal transition via inhibiting Wnt/β-catenin pathway in lung adenocarcinoma. Discov Oncol 2022; 13:98. [PMID: 36192568 PMCID: PMC9530106 DOI: 10.1007/s12672-022-00564-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/11/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Invasion and metastasis are hallmark characteristics of cancer and the main causes of death in cancer patients. Studies have shown that epithelial-mesenchymal transition (EMT) plays significant role in tumor invasion and metastasis. Fucoxanthin, a carotenoid found in seaweeds, has been proved to have anti-tumor effects. Our study aimed to research the role of fucoxanthin on proliferation, apoptosis, migration and EMT of two types of LUAD cells. METHODS Cell migration and invasion were examined by Wound-healing and Transwell assays. Western blot assay was used to detect the expression levels of apoptosis-related proteins, EMT-related proteins and β-catenin. Immunohistochemistry was used to detect the expression of β-catenin in human lung adenocarcinoma tissues and corresponding para-cancerous tissues. RESULTS Our results revealed that fucoxanthin depressed the proliferation and induced apoptosis in A549 and NCI-H1299 cells. Moreover, fucoxanthin reversed TGF-β1-induced EMT and cell motility. Meanwhile, we disclosed that fucoxanthin and XAV939 had similar effect on β-catenin, EMT protein and cell motility. What is more, immunohistochemical results revealed that the high expression rate and abnormal expression rate of β-catenin in cancer tissues was significantly higher than that in para-cancerous tissues. CONCLUSION Taken together, the findings of our research highlight a novel role for fucoxanthin in NSCLC cells, which might be a potentially effective anti-tumor agent for the treatment of LUAD patients.
Collapse
Affiliation(s)
- Heqi Luan
- Department of Respiratory Medicine, Τhe Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116027 Liaoning People’s Republic of China
| | - Lina Yan
- Department of Respiratory Medicine, Τhe Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116027 Liaoning People’s Republic of China
| | - Yuanyuan Zhao
- Department of Respiratory Medicine, Τhe Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116027 Liaoning People’s Republic of China
| | - Xuejiao Ding
- Department of Respiratory Medicine, Τhe Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116027 Liaoning People’s Republic of China
| | - Lihua Cao
- Department of Respiratory Medicine, Τhe Second Hospital Affiliated to Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116027 Liaoning People’s Republic of China
| |
Collapse
|
|
14
|
Zhang Y, Ye F, Gao X. MCA-Net: Multi-Feature Coding and Attention Convolutional Neural Network for Predicting lncRNA-Disease Association. IEEE/ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2022; 19:2907-2919. [PMID: 34283719 DOI: 10.1109/tcbb.2021.3098126] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
With the advent of the era of big data, it is troublesome to accurately predict the associations between lncRNAs and diseases based on traditional biological experiments due to its time-consuming and subjective. In this paper, we propose a novel deep learning method for predicting lncRNA-disease associations using multi-feature coding and attention convolutional neural network (MCA-Net). We first calculate six similarity features to extract different types of lncRNA and disease feature information. Second, a multi-feature coding method is proposed to construct the feature vectors of lncRNA-disease association samples by integrating the six similarity features. Furthermore, an attention convolutional neural network is developed to identify lncRNA-disease associations under 10-fold cross-validation. Finally, we evaluate the performance of MCA-Net from different perspectives including the effects of the model parameters, distinct deep learning models, and the necessity of attention mechanism. We also compare MCA-Net with several state-of-the-art methods on three publicly available datasets, i.e., LncRNADisease, Lnc2Cancer, and LncRNADisease2.0. The results show that our MCA-Net outperforms the state-of-the-art methods on all three dataset. Besides, case studies on breast cancer and lung cancer further verify that MCA-Net is effective and accurate for the lncRNA-disease association prediction.
Collapse
|
|
15
|
Hu Q, Ma H, Chen H, Zhang Z, Xue Q. LncRNA in tumorigenesis of non-small-cell lung cancer: From bench to bedside. Cell Death Dis 2022; 8:359. [PMID: 35963868 PMCID: PMC9376075 DOI: 10.1038/s41420-022-01157-4] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/01/2022] [Accepted: 08/03/2022] [Indexed: 12/12/2022]
Abstract
Lung cancer has been one of the leading causes of cancer-related death worldwide, and non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer morbidity, yet the pathogenesis of NSCLC has not been fully elucidated. Recently, long-chain non-coding RNA (lncRNA) has attracted widespread attention. LncRNA is a type of non-coding RNA whose transcript length exceeds 200 nucleotides. After constant research, academics updated their understanding of lncRNA, especially its role in the biological processes of cancer cells, including epigenetic regulation, cell proliferation, and cell differentiation. Notably, examination of lncRNAs could serve as potential hallmarks for clinicopathological features, long-term prognosis, and drug sensitivity. Therefore, it is necessary to explore the functions of lncRNA in NSCLC and innovate potential strategies against NSCLC based on lncRNA-related research. Herein, we reviewed the functions of lncRNA in the occurrence, diagnosis, treatment, and prognosis of NSCLC, which not only help promote a comprehensive view of lncRNA in NSCLC, but also shed light on the potential of lncRNA-based diagnosis and treatment of NSCLC.
Collapse
Affiliation(s)
- Qin Hu
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.,Medical School of Nantong University, Nantong, China
| | - Huiyun Ma
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.,Medical School of Nantong University, Nantong, China
| | - Hongyu Chen
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.,Medical School of Nantong University, Nantong, China
| | - Zhouwei Zhang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.,Medical School of Nantong University, Nantong, China
| | - Qun Xue
- Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
| |
Collapse
|
|
16
|
Zhang H, Wang SQ, Wang L, Lin H, Zhu JB, Chen R, Li LF, Cheng YD, Duan CJ, Zhang CF. m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression. Cell Death Dis 2022; 13:657. [PMID: 35902569 PMCID: PMC9334586 DOI: 10.1038/s41419-022-05050-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 06/14/2022] [Accepted: 06/28/2022] [Indexed: 01/21/2023]
Abstract
Gefitinib has been widely applied for the treatment of lung adenocarcinoma (LUAD). However, the long-term application of gefitinib usually leads to acquired drug resistance in tumour patients, resulting in clinical treatment failure. Small nucleolar host gene 17 (SNHG17) has been shown to play a regulatory role in LUAD progression. Nevertheless, the role of SNHG17 in LUAD gefitinib resistance remains elusive. The expression pattern of SNHG17 was examined in tissues and cell lines of gefitinib-sensitive and gefitinib-resistant LUAD, respectively. Gain- and loss-of-function experiments were employed to assess the biological functions of SNHG17 in cell proliferation and apoptosis, as well as aggressive phenotypes of LUAD cells. MeRIP-qPCR and colorimetric quantificational analysis were performed to detect m6A modifications and contents. Fluorescence in situ hybridisation (FISH) and subcellular fractionation analysis were used to reveal the distribution of SNHG17. RIP and ChIP assays were performed to further validate the SNHG17/EZH2/LATS2 regulatory axis. A xenograft tumour growth assay was conducted to evaluate the role of SNHG17 in LUAD gefitinib resistance in vivo. SNHG17 was upregulated in gefitinib-resistant LUAD tissues and cell lines. Functional assays showed that SNHG17 aggravated the malignant phenotypes of gefitinib-resistant LUAD cells. In addition, METTL3-mediated N6-methyladenosine modification could induce the upregulation of SNHG17by stabilising its RNA transcript. Mechanistically, SNHG17 epigenetically repressed the expression of LATS2 by recruiting EZH2 to the promoter region of LATS2. The regulatory role of the SNHG17/EZH2/LATS2 axis in LUAD gefitinib resistance was further supported in vivo. Collectively, our findings suggested that SNHG17 induced by METTL3 could promote LUAD gefitinib resistance by epigenetically repressing LATS2 expression.
Collapse
Affiliation(s)
- Heng Zhang
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China ,grid.216417.70000 0001 0379 7164Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China ,Hunan Engineering Research Center for Pulmonary Nodules Precise Diagosis&Treatment, 410008 Changsha, Hunan Province P. R. China ,grid.452223.00000 0004 1757 7615National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, 410008 Hunan Province P. R. China
| | - Shao-Qiang Wang
- grid.449428.70000 0004 1797 7280Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029 Shandong Province P. R. China
| | - Li Wang
- grid.452708.c0000 0004 1803 0208Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province P. R. China ,grid.452708.c0000 0004 1803 0208Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan Province P. R. China
| | - Hang Lin
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China
| | - Jie-Bo Zhu
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China
| | - Ri Chen
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China
| | - Lin-Feng Li
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China
| | - Yuan-Da Cheng
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China
| | - Chao-Jun Duan
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China
| | - Chun-Fang Zhang
- grid.216417.70000 0001 0379 7164Department of General Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China ,grid.216417.70000 0001 0379 7164Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008 Hunan Province P. R. China ,Hunan Engineering Research Center for Pulmonary Nodules Precise Diagosis&Treatment, 410008 Changsha, Hunan Province P. R. China ,grid.452223.00000 0004 1757 7615National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, 410008 Hunan Province P. R. China
| |
Collapse
|
|
17
|
Long non-coding RNAs involved in different steps of cancer metastasis. Clin Transl Oncol 2022; 24:997-1013. [PMID: 35119654 DOI: 10.1007/s12094-021-02761-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 12/14/2021] [Indexed: 11/09/2022]
Abstract
Non-proteincoding transcripts bearing 200 base pairs known as long non-coding RNAs (lncRNAs) play a role in a variety of molecular mechanisms, including cell differentiation, apoptosis and metastasis. Previous studies have suggested that frequently dysregulated lncRNAs play a crucial role in various aspects of cancer metastasis. Metastasis is the main leading cause of death in cancer. The role of lncRNAs in different stages of metastasis is the subject of this review. Based on in vitro and in vivo investigations on metastasis, we categorized lncRNAs into distinct stages of metastasis including angiogenesis, invasion, intravasation, survival in circulation, and extravasation. The involvement of lncRNAs in angiogenesis and invasion has been extensively studied. Here, we comprehensively discuss the role and functions of these lncRNAs with a particular focus on the molecular mechanisms.
Collapse
|
|
18
|
Shin DS, Park K, Garon E, Dubinett S. Targeting EZH2 to overcome the resistance to immunotherapy in lung cancer. Semin Oncol 2022; 49:306-318. [PMID: 35851153 DOI: 10.1053/j.seminoncol.2022.06.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 06/08/2022] [Accepted: 06/11/2022] [Indexed: 12/22/2022]
Abstract
Unleashing the immune system to fight cancer has been a major breakthrough in cancer therapeutics since 2014 when anti-PD-1 antibodies (pembrolizumab and nivolumab) were approved for patients with metastatic melanoma. Therapeutic indications have rapidly expanded for many types of advanced cancer, including lung cancer. A variety of antibodies targeting the PD-1/PD-L1 checkpoint are contributing to this paradigm shift. The field now confronts two salient challenges: first, to improve the therapeutic outcome given the low response rate across the histologies; second, to identify biomarkers for improved patient selection. Pre-clinical and clinical studies are underway to evaluate combinatorial treatments to improve the therapeutic outcome paired with correlative studies to identify the factors associated with response and resistance. One of the emerging strategies is to combine epigenetic modifiers with immune checkpoint blockade (ICB) based on the evidence that targeting epigenetic elements can enhance anti-tumor immunity by reshaping the tumor microenvironment (TME). We will briefly review pleotropic biological functions of enhancer of zeste homolog 2 (EZH2), the enzymatic subunit of polycomb repressive complex 2 (PRC2), clinical developments of oral EZH2 inhibitors, and potentially promising approaches to combine EZH2 inhibitors and PD-1 blockade for patients with advanced solid tumors, focusing on lung cancer.
Collapse
Affiliation(s)
- Daniel Sanghoon Shin
- Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA; VA Greater Los Angeles Healthcare System, Division of Hematology/Oncology, CA, USA; Member of Molecular Biology Institute, UCLA, CA, USA; Member of Jonsson Comprehensive Cancer Center, UCLA, CA, USA.
| | - Kevin Park
- Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA
| | - Edward Garon
- Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA; Member of Jonsson Comprehensive Cancer Center, UCLA, CA, USA
| | - Steven Dubinett
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California Los Angeles, Los Angeles, CA, USA; Departments of Pathology, Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology University of California Los Angeles, CA, USA; VA Greater Los Angeles Healthcare System, Division of Hematology/Oncology, CA, USA; Member of Molecular Biology Institute, UCLA, CA, USA; Member of Jonsson Comprehensive Cancer Center, UCLA, CA, USA
| |
Collapse
|
|
19
|
Chen L, Xie Y, Yu M, Gou Q. Long Noncoding RNAs in Lung Cancer: From Disease Markers to Treatment Roles. Cancer Manag Res 2022; 14:1771-1782. [PMID: 35634537 PMCID: PMC9132104 DOI: 10.2147/cmar.s365762] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 05/09/2022] [Indexed: 12/28/2022] Open
Abstract
There is an urgent need to identify reliable biomarkers that can be used in early diagnosis, prognostication prediction and as possible therapeutic targets for lung cancer due to its current poor prognosis. Long noncoding RNAs (lncRNAs) have recently attracted additional attention due to their potential role in carcinogenesis, invasion and metastasis. Issues involved in the biofunctions and regulatory mechanisms of oncogenic and tumor-suppressive lncRNAs in lung cancer are discussed. Some lncRNAs have shown good diagnostic value, especially in combination with conventional serum protein markers. The use of antisense oligonucleotides, small molecules and RNA interference techniques have shown promise as direct therapeutic tools for targeting lncRNAs in preclinical studies. The biomarker function of lncRNAs may also indirectly involved in tumor therapy as a reference to conventional therapy. Overall, the concept of using lncRNAs as biomarkers for prognostication and intervention in lung cancer is still in its infancy, and only with more in-depth studies could they have a significant impact.
Collapse
Affiliation(s)
- Lin Chen
- Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Yuxin Xie
- Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Laboratory of Molecular Diagnosis of Cancer, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Min Yu
- Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Qiheng Gou
- Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Correspondence: Qiheng Gou, Department of Head and Neck Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Xiang, Wuhou District, Chengdu, 610041, People’s Republic of China, Tel +86-28-85423278, Email
| |
Collapse
|
|
20
|
Qin X, Yin Q, Gao J, Shi X, Tang J, Hao L, Li P, Zhu J, Wang Y. Prognostic role of SPRY4-IT1 in female breast carcinoma and malignant tumors of the reproductive system: A meta-analysis. Medicine (Baltimore) 2022; 101:e28969. [PMID: 35482980 PMCID: PMC9276090 DOI: 10.1097/md.0000000000028969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 02/01/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND The prognostic value of SPRY4-Intronic transcript 1 (SPRY4-IT1) in women suffering from breast carcinoma and malignant tumors of the reproductive system remains to be ascertained. Therefore, this paper attempted to assess the relationship between SPRY4-IT1 with the clinicopathological indicators and survival analysis in women suffering from breast carcinoma and malignant tumors of their reproductive organs through meta-analysis. METHOD Related literature retrieved from Cochrane Library, Ovid, Embase, PubMed, the CNKI, and the Web of Science databases were reviewed. The latest article search was updated to September 1, 2021. The outcome indicators included as effective measures in the study were hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI). The Stata 12.0 software was used to analyze the data. RESULTS The elevated SPRY4-IT1 levels were indicative of poor overall survival (OS) [HR = 2.44, 95% CI = 1.35-4.43, P < .05], and were not related to Disease-Free Survival (DFS) [HR = 1.61, 95% CI = 0.50-5.18, P = .43] in female patients suffering from malignant tumors. In terms of lymph node metastasis (LNM) for the association between long noncoding RNA SPRY4-IT1(LncRNA SPRY4-IT1) and OS, elevated LncRNA SPRY4-IT1 implied poor OS with LNM [HR = 2.79, 95% CI: 1.81-4.28, P < .001]. Based on the aspect of the LNM for the association between LncRNA SPRY4-IT1 and DFS, SPRY4-IT1 was not correlated with DFS [HR = 0.97, 95% CI: 0.73-1.28, P = .81]. SPRY4-IT1 in the TNM stage was not related to OS [HR = 1.43, 95% CI: 0.55-3.70, P = .46]. In the TNM stage, SPRY4-IT1 was not related to DFS [HR = 1.68, 95% CI: 0.92-3.06, P = .09]. SPRY4-IT1 was found to be associated with lymph node metastasis (OR = 4.15, 95% CI: 2.75-6.25, P = .000) and TNM stage (OR = 2.89, 95% CI: 1.51-7.27 P = .02). No significant correlation was noted between SPRY4-IT1 and the age of the patients (OR = 0.89, 95% CI: 0.61-1.29 P = .54). CONCLUSIONS Thus, this study provides evidence-based medical evidence for the target treatment of female breast carcinoma and malignant tumors of the reproductive system. The elevated level of SPRY4-IT1 was associated with poor prognosis of female breast cancer patients and of those having malignant tumors in their reproductive organs. In addition, the SPRY4-IT1 expression was also associated with the disease progression and metastasis.
Collapse
Affiliation(s)
- Xiaoru Qin
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
| | - Qifan Yin
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
| | - Jin Gao
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
| | - Xiaoming Shi
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
| | - Jiachen Tang
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
- North China University of Science and Technology, Tangshan, Hebei, PR China
| | - Lingling Hao
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
- North China University of Science and Technology, Tangshan, Hebei, PR China
| | - Pengfei Li
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
- North China University of Science and Technology, Tangshan, Hebei, PR China
| | - Jia Zhu
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
- North China University of Science and Technology, Tangshan, Hebei, PR China
| | - Yuexin Wang
- Hebei General Hospital, Shijiazhuang, Hebei, PR China
| |
Collapse
|
|
21
|
Yang S, Huang Y, Zhao Q. Epigenetic Alterations and Inflammation as Emerging Use for the Advancement of Treatment in Non-Small Cell Lung Cancer. Front Immunol 2022; 13:878740. [PMID: 35514980 PMCID: PMC9066637 DOI: 10.3389/fimmu.2022.878740] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 03/21/2022] [Indexed: 12/26/2022] Open
Abstract
Lung cancer remains one of the most common malignancies in the world. Nowadays, the most common lung cancer is non-small cell lung cancer (NSCLC), namely, adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Epigenetic alterations that refer to DNA methylation, histone modifications, and noncoding RNA expression, are now suggested to drive the genesis and development of NSCLC. Additionally, inflammation-related tumorigenesis also plays a vital role in cancer research and efforts have been attempted to reverse such condition. During the occurrence and development of inflammatory diseases, the immune component of inflammation may cause epigenetic changes, but it is not always certain whether the immune component itself or the stimulated host cells cause epigenetic changes. Moreover, the links between epigenetic alterations and cancer-related inflammation and their influences on the human cancer are not clear so far. Therefore, the connection between epigenetic drivers, inflammation, and NSCLC will be summarized. Investigation on such topic is most likely to shed light on the molecular and immunological mechanisms of epigenetic and inflammatory factors and promote the application of epigenetics in the innovative diagnostic and therapeutic strategies for NSCLC.
Collapse
Affiliation(s)
- Shuo Yang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- *Correspondence: Shuo Yang, ; Yang Huang, ; Qi Zhao,
| | - Yang Huang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- *Correspondence: Shuo Yang, ; Yang Huang, ; Qi Zhao,
| | - Qi Zhao
- Cancer Centre, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, Macau SAR, China
- MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau, Macau SAR, China
- *Correspondence: Shuo Yang, ; Yang Huang, ; Qi Zhao,
| |
Collapse
|
|
22
|
Ghafouri-Fard S, Khoshbakht T, Taheri M, Shojaei S. A Review on the Role of SPRY4-IT1 in the Carcinogenesis. Front Oncol 2022; 11:779483. [PMID: 35096580 PMCID: PMC8792834 DOI: 10.3389/fonc.2021.779483] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 12/23/2021] [Indexed: 12/24/2022] Open
Abstract
Sprouty RTK signaling antagonist 4-intronic transcript 1 (SPRY4-IT1) is a long non-coding RNA (lncRNA) encoded by a gene located on 5q31.3. This lncRNA has a possible role in the regulation of cell growth, proliferation, and apoptosis. Moreover, since SPRY4-IT1 controls levels of lipin 2, it is also involved in the biosynthesis of lipids. During the process of biogenesis, SPRY4-IT1 is produced as a primary transcript which is then cleaved to generate a mature transcript which is localized in the cytoplasm. SPRY4-IT1 has oncogenic roles in diverse tissues. A possible route of participation of SPRY4-IT1 in the carcinogenesis is through sequestering miRNAs such as miR-101-3p, miR-6882-3p and miR-22-3p. The sponging effect of SPRY4-IT1 on miR-101 has been verified in colorectal cancer, osteosarcoma, cervical cancer, bladder cancer, gastric cancer and cholangiocarcinoma. SPRY4-IT1 has functional interactions with HIF-1α, NF-κB/p65, AMPK, ZEB1, MAPK and PI3K/Akt signaling. We explain the role of SPRY4-IT1 in the carcinogenesis according to evidence obtained from cell lines, xenograft models and clinical studies.
Collapse
Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tayyebeh Khoshbakht
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyedpouzhia Shojaei
- Department of Critical Care Medicine, Imam Hossein Medical and Educational Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
23
|
Ghahramani Almanghadim H, Ghorbian S, Khademi NS, Soleymani Sadrabadi M, Jarrahi E, Nourollahzadeh Z, Dastani M, Shirvaliloo M, Sheervalilou R, Sargazi S. New Insights into the Importance of Long Non-Coding RNAs in Lung Cancer: Future Clinical Approaches. DNA Cell Biol 2021; 40:1476-1494. [PMID: 34931869 DOI: 10.1089/dna.2021.0563] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
In mammals, a large part of the gene expression products come from the non-coding ribonucleotide sequences of the protein. These short and long sequences are within the range of tens to hundreds of nucleotides, encompassing more than 200 RNA molecules, and their function is known as the molecular structure of long non-coding RNA (lncRNA). LncRNA molecules are unique nucleotides that have a substantial role in epigenetic regulation, transcription, and post-transcriptional modifications in different ways. According to the results of recent studies, lncRNAs have been shown to assume various roles, including tumor suppression or oncogenic functions in common types of cancer such as lung and breast cancer. These non-coding RNAs (ncRNAs) play a pivotal role in activating transcription factors, managing the ribonucleoproteins, the framework for collecting co-proteins, intermittent processing regulations, chromatin status alterations, and maintaining the control within the cell. Cutting-edge technologies have been introduced to disclose several types of lncRNAs within the nucleus and the cytoplasm, which have accomplished important achievements that are applicable in medicine. Due to these efforts, various data centers have been created to facilitate and modify scientific information related to these molecules, including detection, classification, biological evolution, gene status, spatial structure, status, and location of these small molecules. In the present study, we attempt to present the impacts of these ncRNAs on lung cancer with an emphasis on their mechanisms and functions.
Collapse
Affiliation(s)
| | - Saeed Ghorbian
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Nazanin Sadat Khademi
- Department of Genetics, Faculty of Biological Science, Shahid Beheshti University, Tehran, Iran
| | | | - Esmaeil Jarrahi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Zahra Nourollahzadeh
- Department of Biological Science, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Masomeh Dastani
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Milad Shirvaliloo
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| |
Collapse
|
|
24
|
Li W, Soufiany I, Lyu X, Lu C, Wei Y, Shi Z, You Y. SP1-upregulated LBX2-AS1 promotes the progression of glioma by targeting the miR-491-5p/LIF axis. J Cancer 2021; 12:6989-7002. [PMID: 34729101 PMCID: PMC8558668 DOI: 10.7150/jca.63289] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 09/14/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Mounting evidences have shown the importance of lncRNAs in carcinogenesis and cancer progression. LBX2-AS1 is identified as an oncogenic lncRNA that is abnormally expressed in gastric cancer and lung cancer samples. This study aims to explore the potential role of LBX2-AS1 in regulating proliferation and EMT in glioma, and the underlying mechanism. Methods: Relative levels of LBX2-AS1 in glioma samples and cell lines were detected by qRT-PCR and FISH. In vivo and in vitro regulatory effects of LBX2-AS1 on proliferation and EMT were examined in the xenograft glioma model and glioma cells. The interaction between SP1 and LBX2-AS1 was assessed by ChIP. Through bioinformatic analyses, dual-luciferase reporter assay, RIP and Western blot, the regulation of LBX2-AS1 and miR-491-5p on the target gene LIF was identified. Results: LBX2-AS1 was upregulated in glioma samples and cell lines, and its transcription was promoted by binding to the transcription factor SP1. As a lncRNA mainly distributed in the cytoplasm, LBX2-AS1 sponge miR-491-5p to further upregulate LIF. The subsequent activated LIF/STAT3 signaling was responsible for promoting proliferation and EMT in glioma. Conclusion: LBX2-AS1 is upregulated by SP1 in glioma, which promotes the progression of glioma by targeting the miR-491-5p/LIF axis. In view of this, LBX2-AS1 is suggested as a novel diagnostic biomarker and therapeutic target of glioma.
Collapse
Affiliation(s)
- Wentao Li
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Ismatullah Soufiany
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Xiao Lyu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Chenfei Lu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Yutian Wei
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
| | - Zhumei Shi
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.,Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, Jiangsu, China
| | - Yongping You
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.,Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, Jiangsu, China
| |
Collapse
|
|
25
|
Jiang J, Lu Y, Zhang F, Huang J, Ren XL, Zhang R. The Emerging Roles of Long Noncoding RNAs as Hallmarks of Lung Cancer. Front Oncol 2021; 11:761582. [PMID: 34692550 PMCID: PMC8529012 DOI: 10.3389/fonc.2021.761582] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 09/23/2021] [Indexed: 12/26/2022] Open
Abstract
Noncoding ribonucleic acids (ncRNAs) are closely associated with tumor initiation, growth, and progress in lung cancer. Long ncRNAs (lncRNAs), as one of the three subclasses of ncRNAs, play important roles in chromatin modification, transcription, and post-transcriptional processing. Various lncRNAs have recently been reported to be dysfunctional or dysregulated in cancers and have pro- or anti-tumor potential. Importantly, as a new class of cancer biomarkers, studies have demonstrated the plausibility of using certain subsets of lncRNAs as promising diagnostic, therapeutic, or prognostic strategies to manage cancers. This review focuses on lncRNAs associated with hallmarks of lung cancer, especially those discovered in the last five years. The expression levels of these lncRNAs in tumor samples are discussed, alongside their mechanisms of action, drug resistance, and potential as diagnostic and prognostic markers for lung cancer.
Collapse
Affiliation(s)
- Jun Jiang
- Department of Health Service, Fourth Military Medical University, Xi'an, China.,Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, China
| | - Yuan Lu
- Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,Department of Respiratory and Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Fang Zhang
- Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jie Huang
- Department of Respiratory and Critical Care Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Xin-Ling Ren
- Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,Department of Pulmonary Medicine, Shenzhen General Hospital, Shenzhen University, Shenzhen, China
| | - Rui Zhang
- State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, China
| |
Collapse
|
|
26
|
Hao A, Wang Y, Stovall DB, Wang Y, Sui G. Emerging Roles of LncRNAs in the EZH2-regulated Oncogenic Network. Int J Biol Sci 2021; 17:3268-3280. [PMID: 34512145 PMCID: PMC8416728 DOI: 10.7150/ijbs.63488] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 07/16/2021] [Indexed: 12/15/2022] Open
Abstract
Cancer is a life-threatening disease, but cancer therapies based on epigenetic mechanisms have made great progress. Enhancer of zeste homolog 2 (EZH2) is the key catalytic component of Polycomb repressive complex 2 (PRC2) that mediates the tri-methylation of lysine 27 on histone 3 (H3K27me3), a well-recognized marker of transcriptional repression. Mounting evidence indicates that EZH2 is elevated in various cancers and associates with poor prognosis. In addition, many studies revealed that EZH2 is also involved in transcriptional repression dependent or independent of PRC2. Meanwhile, long non-coding RNAs (lncRNAs) have been reported to regulate numerous and diverse signaling pathways in oncogenesis. In this review, we firstly discuss functional interactions between EZH2 and lncRNAs that determine PRC2-dependent and -independent roles of EZH2. Secondly, we summarize the lncRNAs regulating EZH2 expression at transcription, post-transcription and post-translation levels. Thirdly, we review several oncogenic pathways cooperatively regulated by lncRNAs and EZH2, including the Wnt/β-catenin and p53 pathways. In conclusion, lncRNAs play a key role in the EZH2-regulated oncogenic network with many fertile directions to be explored.
Collapse
Affiliation(s)
- Aixin Hao
- Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin 150040, China
| | - Yunxuan Wang
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Daniel B Stovall
- College of Arts and Sciences, Winthrop University, Rock Hill, SC 29733, the United States
| | - Yu Wang
- Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin 150040, China
| | - Guangchao Sui
- Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin 150040, China
| |
Collapse
|
|
27
|
Ranjan S, Jain S, Bhargava A, Shandilya R, Srivastava RK, Mishra PK. Lateral flow assay-based detection of long non-coding RNAs: A point-of-care platform for cancer diagnosis. J Pharm Biomed Anal 2021; 204:114285. [PMID: 34333453 DOI: 10.1016/j.jpba.2021.114285] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/23/2021] [Accepted: 07/23/2021] [Indexed: 12/13/2022]
Abstract
Lateral flow assay (LFA) is a flexible, simple, low-costpoint-of-care platform for rapid detection of disease-specific biomarkers. Importantly, the ability of the assay to capture the circulating bio-molecules has gained significant attention, as it offers a potential minimal invasive system for early disease diagnosis and prognosis. In the present article, we review an innovative concept of LFA-based detection of circulating long non-coding RNAs (lncRNAs), one of the key regulators of fundamental biological processes. In addition, their disease-specific expression pattern and presence in biological fluids at differential levels make them excellent biomarker candidates for cancer detection. Our article also provides an update on the requirements for developing and improving such systems and discusses the key aspects of material selection, operational concepts, principles and conceptual design. We assume that the reviewed points will be helpful to improve the diagnostic applicability of LFA based lncRNA detection in cancer diagnosis.
Collapse
Affiliation(s)
- Shashi Ranjan
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Surbhi Jain
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Arpit Bhargava
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Ruchita Shandilya
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | | | - Pradyumna Kumar Mishra
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India.
| |
Collapse
|
|
28
|
Lu C, Wei D, Zhang Y, Wang P, Zhang W. Long Non-Coding RNAs as Potential Diagnostic and Prognostic Biomarkers in Breast Cancer: Progress and Prospects. Front Oncol 2021; 11:710538. [PMID: 34527584 PMCID: PMC8436618 DOI: 10.3389/fonc.2021.710538] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 08/09/2021] [Indexed: 01/05/2023] Open
Abstract
Breast cancer is the most common malignancy among women worldwide, excluding non-melanoma skin cancer. It is now well understood that breast cancer is a heterogeneous entity that exhibits distinctive histological and biological features, treatment responses and prognostic patterns. Therefore, the identification of novel ideal diagnostic and prognostic biomarkers is of utmost importance. Long non-coding RNAs (lncRNAs) are commonly defined as transcripts longer than 200 nucleotides that lack coding potential. Extensive research has shown that lncRNAs are involved in multiple human cancers, including breast cancer. LncRNAs with dysregulated expression can act as oncogenes or tumor-suppressor genes to regulate malignant transformation processes, such as proliferation, invasion, migration and drug resistance. Intriguingly, the expression profiles of lncRNAs tend to be highly cell-type-specific, tissue-specific, disease-specific or developmental stage-specific, which makes them suitable biomarkers for breast cancer diagnosis and prognosis.
Collapse
Affiliation(s)
- Cuicui Lu
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Duncan Wei
- Department of Pharmacy, The First Affiliated Hospital of Medical College of Shantou University, Shantou, China
| | - Yahui Zhang
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Peng Wang
- Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
| | - Wen Zhang
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| |
Collapse
|
|
29
|
Huang P, Zhu S, Liang X, Zhang Q, Liu C, Song L. Revisiting Lung Cancer Metastasis: Insight From the Functions of Long Non-coding RNAs. Technol Cancer Res Treat 2021; 20:15330338211038488. [PMID: 34431723 PMCID: PMC8392855 DOI: 10.1177/15330338211038488] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Globally, lung cancer is the most common cause of cancer-related deaths. After
diagnosis at all stages, <7% of patients survive for 10 years. Thus,
diagnosis at later stages and the lack of effective and personalized drugs
reflect a significant need to better understand the mechanisms underpinning lung
cancer progression. Metastasis should be responsible for the high lethality and
recurrence rates seen in lung cancer. Metastasis depends on multiple crucial
steps, including epithelial–mesenchymal transition, vascular remodeling, and
colonization. Therefore, in-depth investigations of metastatic molecular
mechanisms can provide valuable insights for lung cancer treatment. Recently,
long noncoding RNAs (lncRNAs) have attracted considerable attention owing to
their complex roles in cancer progression. In lung cancer, multiple lncRNAs have
been reported to regulate metastasis. In this review, we highlight the major
molecular mechanisms underlying lncRNA-mediated regulation of lung cancer
metastasis, including (1) lncRNAs acting as competing endogenous RNAs, (2)
lncRNAs regulating the transduction of several signal pathways, and (3) lncRNA
coordination with enhancer of zeste homolog 2. Thus, lncRNAs appear to execute
their functions on lung cancer metastasis by regulating angiogenesis, autophagy,
aerobic glycolysis, and immune escape. However, more comprehensive studies are
required to characterize these lncRNA regulatory networks in lung cancer
metastasis, which can provide promising and innovative novel therapeutic
strategies to combat this disease.
Collapse
Affiliation(s)
- Peng Huang
- Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China
| | - Shaomi Zhu
- Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China
| | - Xin Liang
- Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China
| | - Qinxiu Zhang
- Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China
| | - Chi Liu
- Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China
| | - Linjiang Song
- Reproductive & Women-Children Hospital, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, P.R. China
| |
Collapse
|
|
30
|
Li Y, Zhai Y, Chen Y. GATA1-induced upregulation of LINC01503 promotes carboplatin resistance in ovarian carcinoma by upregulating PD-L1 via sponging miR-766-5p. J Ovarian Res 2021; 14:108. [PMID: 34425872 PMCID: PMC8383404 DOI: 10.1186/s13048-021-00856-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/05/2021] [Indexed: 01/15/2023] Open
Abstract
Background Ovarian Carcinoma (OCa) is a high-mortality malignancy derived from female reproductive system. Increasing evidence has identified long non-coding RNAs (lncRNAs) as important regulators in OCa chemoresistance. In this study, we intended to explore the role of LINC01503 in OCa resistance to carboplatin (CBP). Methods Gene expression was measured by reverse transcription-quantitative PCR (RT-qPCR) in OCa cells. Western blot was adopted to detect protein levels of GATA1, PD-L1, E-cadherin, N-cadherin, Vimentin, Bcl-2, Bax, cleaved caspase-3. To assess the effects of LINC01503 on the resistance of OCa cells to CBP, Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry experiments were performed to evaluate half-maximal inhibitory concentration (IC50), cell viability, migrative and invasive ability, as well as cell apoptosis. Dual-luciferase reporter assay was employed to assess the associations between the genes. Results LINC01503 was upregulated in CBP-resistant OCa cells. LINC01503 knockdown reduced CBP resistance in OCa cells. Besides, GATA-binding protein 1 (GATA1) activated LINC01503 transcription in CBP-resistant OCa cells. MiR-766-5p was lowly expressed in CBP-resistant cells and confirmed as a target for LINC01503. In addition, miR-766-5p overexpression increased CBP sensitivity in OCa cells. PD-L1 was verified as the target of miR-766-5p. Besides, LINC01503 upregulated PD-L1 level by regulating miR-766-5p. Furthermore, rescue experiments showed that PD-L1 overexpression abrogated the inhibited impacts of blocking LINC01503 on CBP resistance in OCa cells. Conclusion GATA1-induced LINC01503 expedited CBP resistance in OCa cells via the miR-766-5p/PD-L1 axis, providing a new target for improving the efficacy of OCa chemotherapy. Graphical Abstract ![]()
Collapse
Affiliation(s)
- Yao Li
- Department of Gynaecology and Obstetrics, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Workers Stadium Road, Chaoyang District, Beijing, 100020, China.
| | - Yan Zhai
- Department of Gynaecology and Obstetrics, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Workers Stadium Road, Chaoyang District, Beijing, 100020, China
| | - Yuxuan Chen
- Department of Gynecology, Capital Medical University, Beijing, 100071, China
| |
Collapse
|
|
31
|
Qi Q, Chen C, Liu C, Zhang B, Ma Y, Zhang H, Huang W, Wang C. Linc8087 predicts favorable prognosis and inhibits cell migration and invasion in NSCLC. Pathol Res Pract 2021; 225:153569. [PMID: 34391179 DOI: 10.1016/j.prp.2021.153569] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 07/28/2021] [Accepted: 07/28/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Non-small cell lung cancer (NSCLC) is the most common cancer and has poor prognosis. Long non-coding RNA(LncRNA) plays important roles in the regulation of cell migration in various types of cancer. In this study, we aimed to demonstrate the function of linc8087 in regulating cell migration and invasion in NSCLC cells. METHODS A lncRNA microarray was used to identify differentially expressed lncRNAs between NSCLC tissues and normal tissues. RT-qPCR was used to confirm the expression of linc8087 in tumor tissues. The association between linc8087 expression and clinicopathological characteristics was analyzed. RNA fluorescence in situ hybridization (FISH) was performed to observe the subcellular localization of linc8087. We investigated the effects of linc8087 expression on cell migration and invasion by wound healing assay, Transwell and invasion assays. The Human Tumor Metastasis RT2 Profiler PCR Array was used to detect and analyze the mRNA levels of 84 genes involved in metastasis. RESULTS We found that linc8087 expression was obviously decreased in both NSCLC tissues and cell lines compared with paired normal tissues and a normal bronchial epithelium cell line. Low expression of linc8087 was significantly associated with poor survival. In addition, linc8087 was an independent risk factor for survival. Overexpressed linc8087 inhibited cell migration and invasion in A549 and PC9 cell lines. Knockdown of linc8087 promoted cell migration and invasion. The result of RT2 Profiler PCR Array showed that overexpressed linc8087 upregulated the expression of the COL4A2, CST7 and FAT1 genes and led to the downregulation of SERPINE1. CONCLUSIONS These results indicate that linc8087 plays a key role in the progression of NSCLC, and it may serve as a meaningful prognostic biomarker as well as a latent therapeutic target in NSCLC patients.
Collapse
Affiliation(s)
- Qi Qi
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin Lung Cancer Center, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| | - Chen Chen
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| | - Chang Liu
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin Lung Cancer Center, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| | - Bin Zhang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin Lung Cancer Center, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| | - Yuchen Ma
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin Lung Cancer Center, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| | - Hua Zhang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin Lung Cancer Center, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| | - Wuhao Huang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin Lung Cancer Center, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| | - Changli Wang
- Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300202, China; National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin 300202, China; Tianjin Lung Cancer Center, Huanhuxi Road, Hexi District, Tianjin 300202, China.
| |
Collapse
|
|
32
|
Abdul-Maksoud RS, Rashad NM, Elsayed WSH, Elsayed RS, Sherif MM, Abbas A, El Shabrawy M. The diagnostic significance of circulating lncRNA ADAMTS9-AS2 tumor biomarker in non-small cell lung cancer among the Egyptian population. J Gene Med 2021; 23:e3381. [PMID: 34312940 DOI: 10.1002/jgm.3381] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/29/2021] [Accepted: 07/19/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Long non-coding RNA ADAM metallopeptidase with thrombospondin type 1 motif, 9 antisense RNA 2 (ADAMTS9-AS2) was recognized as a novel tumor suppressor and plays an important role in the initiation and progression of malignant behavior in human cancers, although its plasma expression and clinical value in patients with non-small cell lung cancer (NSCLC) remain unknown. We aimed to analyze the diagnostic role of ADAMTS9-AS2 and cytokeratin 19 fragmentation antigen (CYFRA 21-1) in NSCLC. METHODS The present study included 80 control subjects, 80 patients with benign lung lesion and 80 NSCLC patients. The expression of ADAMTS9-AS2 in the tissue and plasma was detected by a real-time polymerase chain reaction. Serum CYFRA 21-1 was analyzed using an enzyme-linked immunosorbent assay. RESULTS In comparison with benign lung lesion and controls, tissue and plasma ADAMTS9-AS2 expression were significantly down-regulated in NSCLC (p < 0.001). Decreased ADAMTS9-AS2 expression was associated with TNM stages in NSCLC patients (p < 0.001). Up-regulation of CYFRA 21-1 was reported among NSCLC patients and it was associated with TNM staging. Tissue and plasma ADAMTS9-AS2 expression levels were the predicting factors for NSCLC and they both correlated negatively with CYFRA 21-1 levels. Plasma ADAMTS9-AS2 levels had a significant positive correlation with their tumor tissue levels. Plasma ADAMTS9-AS2 showed a higher sensitivity (95%) and specificity (99.1%) in the diagnosis of NSCLC than CYFRA 21-1 (61.3% sensitivity and 60% specificity). CONCLUSIONS Our results suggested that decreased plasma ADAMTS9-AS2 expression might act as a novel non-invasive tumor biomarker in NSCLC diagnosis. Furthermore, plasma ADAMTS9-AS2 might predict aggressive tumor behavior.
Collapse
Affiliation(s)
- Rehab S Abdul-Maksoud
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Nearmeen M Rashad
- Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Walid S H Elsayed
- Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Rasha S Elsayed
- General Surgery Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Magda M Sherif
- Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ahmad Abbas
- Chest department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | | |
Collapse
|
|
33
|
Zhao L, Jiang L, Zhang M, Zhang Q, Guan Q, Li Y, He M, Zhang J, Wei M. NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay. Oncogene 2021; 40:4919-4929. [PMID: 34163032 PMCID: PMC8321898 DOI: 10.1038/s41388-021-01900-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 05/10/2021] [Accepted: 06/08/2021] [Indexed: 01/09/2023]
Abstract
Previous study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3'-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3'-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3'-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.
Collapse
Affiliation(s)
- Lin Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Longyang Jiang
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Ming Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Qiang Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Qiutong Guan
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Yalun Li
- Department of Anorectal Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Miao He
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Jingdong Zhang
- Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang, China.
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China.
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China.
| |
Collapse
|
|
34
|
Myristoylation-mediated phase separation of EZH2 compartmentalizes STAT3 to promote lung cancer growth. Cancer Lett 2021; 516:84-98. [PMID: 34102285 DOI: 10.1016/j.canlet.2021.05.035] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 01/27/2023]
Abstract
N-myristoylation is a crucial signaling and pathogenic modification process that confers hydrophobicity to cytosolic proteins. Although different large-scale approaches have been applied, a large proportion of myristoylated proteins remain to be identified. EZH2 is overexpressed in lung cancer cells and exerts oncogenic effects via its intrinsic methyltransferase activity. Using a well-established click chemistry approach, we found that EZH2 can be modified by myristoylation at its N-terminal glycine in lung cancer cells. Hydrophobic interaction is one of the main forces driving or stabilizing liquid-liquid phase separation (LLPS), raising the possibility that myristoylation can modulate LLPS by mediating hydrophobic interactions. Indeed, myristoylation facilitates EZH2 to form phase-separated liquid droplets in lung cancer cells and in vitro. Furthermore, we provide evidence that myristoylation-mediated LLPS of EZH2 compartmentalizes its non-canonical substrate, STAT3, and activates STAT3 signaling, ultimately resulting in accelerated lung cancer cell growth. Thus, targeting EZH2 myristoylation may have significant therapeutic efficacy in the treatment of lung cancer. Altogether, these observations not only extend the list of myristoylated proteins, but also indicate that hydrophobic lipidation may serve as a novel incentive to induce or maintain LLPS.
Collapse
|
|
35
|
Xie FW, Liu JC. LncRNA SNHG12 regulates the miR-101-3p/CUL4B axis to mediate the proliferation, migration and invasion of non-small cell lung cancer. Kaohsiung J Med Sci 2021; 37:664-674. [PMID: 34002487 DOI: 10.1002/kjm2.12389] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 02/03/2021] [Accepted: 04/08/2021] [Indexed: 12/13/2022] Open
Abstract
Mounting evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and tumor progression. SNHG12 has been identified in multiple types of malignant tumors. However, the role of SNHG12 in human non-small cell lung cancer (NSCLC) is poorly characterized, and the relevant underlying mechanism remains unclear. The expression levels of SNHG12, miR-101-3p, and CUL4B in collected human NSCLC tumor tissues and NSCLC cell lines were tested via qRT-PCR. Then, NSCLC cellular proliferation, migration and invasion were determined, followed by MTT, scratch and Transwell assays. Dual-luciferase reporter assays and RNA pulldown assays were adopted to explore the target site. Moreover, western blotting was performed to detect the relevant protein expression concerning the CUL4B/PI3K/AKT pathway. This study clarified that SNHG12 knockdown significantly reduced proliferation, migration, invasion and EMT of NSCLC cells. Our data indicated that SNHG12 targeted and negatively regulated miR-101-3p, and this depletion reversed the inhibitory effect of si-SNHG12 on NSCLC cells. Furthermore, CUL4B was confirmed as a functional target of miR-101-3p, and its knockdown resulted in a strong alleviation of the NSLCL cell phenotype, which was enhanced by the silencing of miR-101-3p. Mechanistically, we found that SNHG12 regulated miR-101-3p to modulate the PI3K/AKT pathway mediated by CUL4B.These observations suggested that lncRNA SNHG12-mediated miR-101-3p downregulation regulated the malignant phenotype of NSCLC cells by targeting CUL4B through the PI3K/AKT pathway, which may present a path to novel therapeutic strategies for NSCLC therapy.
Collapse
Affiliation(s)
- Feng-Wen Xie
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ji-Chun Liu
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| |
Collapse
|
|
36
|
Huang J, Xu Y, Wang F, Wang H, Li L, Deng Y, Cai L. Long Noncoding RNA SPRY4-IT1 Modulates Ketamine-Induced Neurotoxicity in Human Embryonic Stem Cell-Derived Neurons through EZH2. Dev Neurosci 2021; 43:9-17. [PMID: 33827085 DOI: 10.1159/000513535] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/02/2020] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE This study aimed to investigate whether long noncoding RNA sprouty receptor tyrosine kinase signaling antagonist 4-intronic transcript 1 (SPRY4-IT1) is involved in the regulation of ketamine-induced neurotoxicity. METHODS Human embryonic stem cells (hESCs) were induced into neurons in vitro and treated with ketamine. Apoptosis and neurite degeneration assays were used to determine ketamine-induced neurotoxicity and qRT-PCR to determine SPRY4-IT1 expression. SPRY4-IT1 was downregulated in hESC-induced neurons to examine its regulation on ketamine-induced neurotoxicity. The correlation between enhancer of zeste homolog 2 (EZH2) and SPRY4-IT1 was also examined. EZH2 was upregulated in SPRY4-IT1-downregualted hESC-induced neurons to further examine its participation in SPRY4-IT1-mediated ketamine neurotoxicity. RESULTS Ketamine-induced dose-dependent apoptosis, neurite degeneration, and SPRY4-IT1 upregulation in hESC-induced neurons. Lentivirus-mediated SPRY4-IT1 downregulation protected ketamine neurotoxicity. EZH2 expression was positively correlated with SPRY4-IT1 in hESC-induced neurons. EZH2 overexpression markedly reversed the protective effects of SPRY4-IT1 knockdown on ketamine neurotoxicity. CONCLUSIONS SPRY4-IT1 is involved in anesthesia-induced neurotoxicity, possibly through the regulation on EZH2 gene.
Collapse
Affiliation(s)
- Jingyuan Huang
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yan Xu
- Department of Anesthesiology, Xi'an Central Hospital, Xi'an, China
| | - Fang Wang
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Haili Wang
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Lu Li
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Yanan Deng
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Liang Cai
- Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| |
Collapse
|
|
37
|
Qie P, Yin Q, Xun X, Song Y, Zhou S, Liu H, Feng J, Tian Z. Long non-coding RNA SPRY4-IT1 as a promising indicator for three field lymph-node dissection of thoracic esophageal carcinoma. J Cardiothorac Surg 2021; 16:48. [PMID: 33757566 PMCID: PMC7988958 DOI: 10.1186/s13019-021-01433-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 03/16/2021] [Indexed: 01/04/2023] Open
Abstract
Background Esophageal squamous cell carcinoma(ESCC) is one of the most common tumors worldwide. Esophagectomy with three-field lymph node dissection(3FLND) is the radical surgical procedure for esophageal cancer. However, 3FLND is not widely used due to it’s higher mortality rate and higher incidence of postoperative complications. There is an urgent need to identify novel biomarkers that can guide the most proper lymph-node dissection in esophageal cancer patients. Method Ninety-two patients with thoracic ESCC undergoing 3FLND were enrolled into our study from the Department of Thoracic Surgery of the Fourth Hospital affiliated to the Hebei Medical University and Hebei General Hospital between Jun 2011 and Dec 2015. Retrospectively collected data from these 92 patients was used to explore the relationship between the lymph-node metastasis、recurrence and the SPRY4-IT1 expression level and to determine whether 3FLND should be performed in patients with thoracic ESCC. Results The findings revealed that the SPRY4-IT1 expression was significantly higher in esophageal cancer tissues than in adjacent noncancerous tissues. (P < 0.01). Furthermore, the high expression of SPRY4-IT1 was significantly correlated with tumor differentiation (P = 0.029), T classification (P = 0.013), lymph node metastasis(P = 0.022) and pathological stage (P = 0.001). The increased expression of SPRY4-IT1 was associated with a higher risk of cervical and superior mediastinal lymph-node metastasis(P = 0.039).However, no significant association was observed between the risk of cervical and superior mediastinal lymph-node recurrence and the SPRY4-IT1 expression level in the thoracic ESCC patients performed 3FLND(P = 0.509). Conclusions Our data support the assumption that the high expression of SPRY4-IT1 is associated with a high risk of lymph node metastasis and it has potential application as a indicator for guiding on three-field lymph node dissection in patients with thoracic ESCC. Randomized controlled trials with a large cohort of patients will be needed to confirm this conclusion in the future.
Collapse
Affiliation(s)
- Peng Qie
- Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China
| | - Qifan Yin
- Hebei General Hospital, 348,West He-Ping Road, Shijiazhuang, 050051, Hebei Province, People's Republic of China
| | - Xuejiao Xun
- Hebei General Hospital, 348,West He-Ping Road, Shijiazhuang, 050051, Hebei Province, People's Republic of China
| | - Yongbin Song
- Hebei General Hospital, 348,West He-Ping Road, Shijiazhuang, 050051, Hebei Province, People's Republic of China
| | - Shaohui Zhou
- Hebei General Hospital, 348,West He-Ping Road, Shijiazhuang, 050051, Hebei Province, People's Republic of China
| | - Huining Liu
- Hebei General Hospital, 348,West He-Ping Road, Shijiazhuang, 050051, Hebei Province, People's Republic of China
| | - Junpeng Feng
- Hebei Chest Hospital, Shijiazhuang, 050041, Hebei Province, People's Republic of China
| | - Ziqiang Tian
- Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, 050035, Hebei Province, People's Republic of China. .,Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050035, Hebei Province, People's Republic of China.
| |
Collapse
|
|
38
|
Bresesti C, Vezzoli V, Cangiano B, Bonomi M. Long Non-Coding RNAs: Role in Testicular Cancers. Front Oncol 2021; 11:605606. [PMID: 33767982 PMCID: PMC7986848 DOI: 10.3389/fonc.2021.605606] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 01/05/2021] [Indexed: 12/13/2022] Open
Abstract
In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such as secondary tumors, infertility, and cardiovascular diseases. It is therefore important to study the impact of lncRNAs in the tumorigenesis of testicular cancer in order to learn how to exploit them in a clinical setting and to substitute more toxic treatments. Eventually, the use of lncRNAs as biomarkers, drug targets, or therapeutics for testicular cancer may represent a valid alternative to that of conventional tools, leading to a better management of this malignancy and its related conditions, and possibly even to the treatment of poor prognosis cases.
Collapse
Affiliation(s)
- Chiara Bresesti
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
| | - Valeria Vezzoli
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
| | - Biagio Cangiano
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Marco Bonomi
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| |
Collapse
|
|
39
|
Jung J, Lee YJ, Kim CH, Ahn S. Landscape of epigenetically regulated lncRNAs and DNA methylation in smokers with lung adenocarcinoma. PLoS One 2021; 16:e0247928. [PMID: 33684161 PMCID: PMC7939300 DOI: 10.1371/journal.pone.0247928] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 02/16/2021] [Indexed: 12/31/2022] Open
Abstract
In this study, we identified long non-coding RNAs (lncRNAs) associated with DNA methylation in lung adenocarcinoma (LUAD) using clinical and methylation/expression data from 184 qualified LUAD tissue samples and 21 normal lung-tissue samples from The Cancer Genome Atlas (TCGA). We identified 1865 differentially expressed genes that correlated negatively with the methylation profiles of normal lung tissues, never-smoker LUAD tissues and smoker LUAD tissues, while 1079 differentially expressed lncRNAs were identified using the same criteria. These transcripts were integrated using ingenuity pathway analysis to determine significant pathways directly related to cancer, suggesting that lncRNAs play a crucial role in carcinogenesis. When comparing normal lung tissues and smoker LUAD tissues, 86 candidate genes were identified, including six lncRNAs. Of the 43 candidate genes revealed by comparing never-smoker LUAD tissues and smoker LUAD tissues, 13 were also different when compared to normal lung tissues. We then investigated the expression of these genes using the Gene Expression of Normal and Tumor Tissues (GENT) and Methylation and Expression Database of Normal and Tumor Tissues (MENT) databases. We observed an inverse correlation between the expression of 13 genes in normal lung tissues and smoker LUAD tissues, and the expression of five genes between the never-smoker and smoker LUAD tissues. These findings were further validated in clinical specimens using bisulfite sequencing, revealing that AGR2, AURKB, FOXP3, and HMGA1 displayed borderline differences in methylation. Finally, we explored the functional connections between DNA methylation, lncRNAs, and gene expression to identify possible targets that may contribute toward the pathogenesis of cigarette smoking-associated LUAD. Together, our findings suggested that differentially expressed lncRNAs and their target transcripts could serve as potential biomarkers for LUAD.
Collapse
Affiliation(s)
- Jiyoon Jung
- Department of Pathology, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, Republic of Korea
| | - Yoo Jin Lee
- Department of Pathology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Chul Hwan Kim
- Department of Pathology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
- * E-mail: (CHK); (SA)
| | - Sangjeong Ahn
- Department of Pathology, International St. Mary’s Hospital, Catholic Kwandong University College of Medicine, Incheon, Republic of Korea
- * E-mail: (CHK); (SA)
| |
Collapse
|
|
40
|
Guo Z, Dai Y, Hu W, Zhang Y, Cao Z, Pei W, Liu N, Nie J, Wu A, Mao W, Chang L, Li B, Pei H, Hei TK, Zhou G. The long noncoding RNA CRYBG3 induces aneuploidy by interfering with spindle assembly checkpoint via direct binding with Bub3. Oncogene 2021; 40:1821-1835. [PMID: 33564066 PMCID: PMC7946627 DOI: 10.1038/s41388-020-01601-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 11/22/2020] [Accepted: 12/02/2020] [Indexed: 01/31/2023]
Abstract
Aneuploidy is a hallmark of genomic instability that leads to tumor initiation, progression, and metastasis. CDC20, Bub1, and Bub3 form the mitosis checkpoint complex (MCC) that binds the anaphase-promoting complex or cyclosome (APC/C), a crucial factor of the spindle assembly checkpoint (SAC), to ensure the bi-directional attachment and proper segregation of all sister chromosomes. However, just how MCC is regulated to ensure normal mitosis during cellular division remains unclear. In the present study, we demonstrated that LNC CRYBG3, an ionizing radiation-inducible long noncoding RNA, directly binds with Bub3 and interrupts its interaction with CDC20 to result in aneuploidy. The 261-317 (S3) residual of the LNC CRYBG3 sequence is critical for its interaction with Bub3 protein. Overexpression of LNC CRYBG3 leads to aneuploidy and promotes tumorigenesis and metastasis of lung cancer cells, implying that LNC CRYBG3 is a novel oncogene. These findings provide a novel mechanistic basis for the pathogenesis of NSCLC after exposure to ionizing radiation as well as a potential target for the diagnosis, treatment, and prognosis of an often fatal disease.
Collapse
Affiliation(s)
- Ziyang Guo
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
- Center for Radiological Research, College of Physician and Surgeons, Columbia University Medical Center, New York, NY, USA
| | - Yingchu Dai
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Wentao Hu
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Yongsheng Zhang
- Department of Pathology, the Second Affiliated Hospital, Medical College of Soochow University, Suzhou, 215123, China
| | - Zhifei Cao
- Department of Pathology, the Second Affiliated Hospital, Medical College of Soochow University, Suzhou, 215123, China
| | - Weiwei Pei
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Ningang Liu
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Jing Nie
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Anqing Wu
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Weidong Mao
- Department of Pathology, the Second Affiliated Hospital, Medical College of Soochow University, Suzhou, 215123, China
| | - Lei Chang
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Bingyan Li
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China
| | - Hailong Pei
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China.
| | - Tom K Hei
- Center for Radiological Research, College of Physician and Surgeons, Columbia University Medical Center, New York, NY, USA.
| | - Guangming Zhou
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China.
| |
Collapse
|
|
41
|
Pu FF, Shi DY, Chen T, Liu YX, Zhong BL, Zhang ZC, Liu WJ, Wu Q, Wang BC, Shao ZW, He TC, Liu JX. SP1-induced long non-coding RNA SNHG6 facilitates the carcinogenesis of chondrosarcoma through inhibiting KLF6 by recruiting EZH2. Cell Death Dis 2021; 12:59. [PMID: 33431838 PMCID: PMC7801621 DOI: 10.1038/s41419-020-03352-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 12/22/2022]
Abstract
Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma cells. Mechanistic study revealed that SNHG6 could recruit EZH2 and maintain high level of H3K27me3 to repress the transcription of tumor-suppressor genes, including KLF6. KLF6 was found to bind to the promoter region of SP1 and restrained its transcription, while SP1 could be recruited to the promoter region of SNHG6 and promoted its transcription to form a positive loop. In summary, this study reveals that SP1-induced SNHG6 forms a positive loop to facilitate the carcinogenesis of chondrosarcoma through the suppression of KLF6 by recruiting EZH2, which manifests the oncogenic function of SNHG6 in chondrosarcoma.
Collapse
Affiliation(s)
- Fei-Fei Pu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - De-Yao Shi
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Ting Chen
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Yu-Xuan Liu
- No.1 Middle School Attached to Central China Normal University, 430223, Wuhan, Hubei Province, P.R. China
| | - Bin-Long Zhong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Zhi-Cai Zhang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Wei-Jian Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Qiang Wu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Bai-Chuan Wang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Zeng-Wu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China
| | - Tong-Chuan He
- Molecular Oncology Laboratory, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC3079, Chicago, IL, 60637, USA
| | - Jian-Xiang Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, P.R. China.
| |
Collapse
|
|
42
|
Xie Y, Zhang S, Lv Z, Long T, Luo Y, Li Z. SOX21-AS1 modulates neuronal injury of MMP +-treated SH-SY5Y cells via targeting miR-7-5p and inhibiting IRS2. Neurosci Lett 2021; 746:135602. [PMID: 33421490 DOI: 10.1016/j.neulet.2020.135602] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 12/21/2020] [Accepted: 12/26/2020] [Indexed: 01/29/2023]
Abstract
Parkinson's disease (PD), caused by the decreased number of dopaminergic neurons in the substantia nigra, is identified as the second most familiar age-dependent neurodegenerative disease to the public. Long non-coding RNAs (lncRNAs) have been reported to participate in the development of PD. In our research, the expression of lncRNA SRY-box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1) was up-regulated in 1-methyl-4-phenylpyridinium (MMP+)-treated SH-SY5Y cells. In addition, SOX21-AS1 depletion weakened the cell injury induced by MMP+. Moreover, SOX21-AS1 knockdown decreased Reactive Oxygen Species (ROS) generation and levels of TNF-α, IL-1β and IL-6, but increased SOD activity. However, SOX21-AS1 up-regulation led to opposite results. Further, SOX21-AS1 could bind with miR-7-5p, whose overexpression relieved MMP+-induced cell injury. Additionally, insulin receptor substrate 2 (IRS2) served as the target gene of miR-7-5p, and its expression was positively modulated by SOX21-AS1. Similarly, IRS2 knockdown also had alleviative effects on cell injury stimulated by MMP+ treatment. In sum up, our study demonstrated a new regulatory network consisted of SOX21-AS1, miR-7-5p and IRS2 in SH-SY5Y cells, supplying with a better comprehension about the pathogenic mechanism of PD.
Collapse
Affiliation(s)
- Yang Xie
- Department of Neurology, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou City, Sichuan Province, 646000, China
| | - Shujiang Zhang
- Department of Neurology, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou City, Sichuan Province, 646000, China
| | - Zhiyu Lv
- Department of Neurology, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou City, Sichuan Province, 646000, China
| | - Ting Long
- Department of Neurology, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou City, Sichuan Province, 646000, China
| | - Ying Luo
- Department of Neurology, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou City, Sichuan Province, 646000, China
| | - Zuoxiao Li
- Department of Neurology, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou City, Sichuan Province, 646000, China.
| |
Collapse
|
|
43
|
Wang J, Li X, Li H, Li X. LncRNA HOXA11-AS regulates the proliferation and epithelial to mesenchymal transition of human skin cancer cells. 3 Biotech 2021; 11:12. [PMID: 33442511 DOI: 10.1007/s13205-020-02557-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 11/17/2020] [Indexed: 12/21/2022] Open
Abstract
LncRNA HOXA11-AS functions as regulator of tumorigenesis of several human cancers. The present study was intended to explore its regulatory control in human skin cancer with emphasis on understanding the underlying molecular mechanism. The results showed significant (P < 0.05) upregulation of lncRNA HOXA11-AS transcript levels in human skin cancer tissues and cell lines. The knockdown of HOXA11-AS significantly (P < 0.05) inhibited the proliferation and colony formation of A375 and HMCB skin cancer cells. Flow cytometry showed that HOXA11-AS knockdown triggered arrest of the A375 and HMCB cells at G2/M check point of cell cycle by inhibiting the expression of cyclin B1. Additionally, western blot analysis showed that HOXA11-AS knockdown resulted in the deactivation of PI3K/AKT/mTOR signaling pathway. The silencing of HOXA11-AS significantly (P < 0.05) inhibited the migration and invasion of the A375 and HMCB skin cancer cells. This was also accompanied by increase in E-cadherin and decrease in N-cadherin expression. Collectively, the results indicate that lncRNA HOXA11-AS regulates the proliferation, migration and invasion of human skin cancer and may exhibit therapeutic potential in the treatment of skin cancer.
Collapse
Affiliation(s)
- Jigang Wang
- Department of Burn and Plastic Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061001 Hebei China
| | - Xiuli Li
- Department of Burn and Plastic Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061001 Hebei China
| | - Hui Li
- Department of Burn and Plastic Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061001 Hebei China
| | - Xin Li
- Department of Burn and Plastic Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061001 Hebei China
| |
Collapse
|
|
44
|
Chen Z, Xiang L, Hu Z, Ou H, Liu X, Yu L, Chen W, Jiang L, Yu Q, Fang Y, Xu Y, Liu Q, Huang Y, Li X, Yang D. Epigenetically silenced linc00261 contributes to the metastasis of hepatocellular carcinoma via inducing the deficiency of FOXA2 transcription. Am J Cancer Res 2021; 11:277-296. [PMID: 33520374 PMCID: PMC7840721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 11/25/2020] [Indexed: 06/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. In recent decades, long non-coding RNAs (lncRNAs) have attracted increasing attention and have been reported to play important roles in human cancers, making them ideal candidates for precise disease assessment and treatment. Our previous study found that the loss of linc00261 was significantly correlated with the malignant biological behaviors of HCC, particularly MVI, and serves as an excellent independent prognostic factor for recurrence-free survival. In this study, our in-depth research demonstrated that linc00261 inhibits epithelial-mesenchymal transition (EMT) in liver cancer cells, thereby suppressing migration, invasion, and the formation of lung metastatic lesions. Moreover, linc00261 and its neighbor gene FOXA2 were positively correlated in HCC, the gain- and loss-of-function analyses indicated that linc00261 transcriptionally promotes the expression of FOXA2. Additionally, bioinformatic analysis and rescue assays confirmed that linc00261 partially suppresses migration, invasion, and EMT by upregulating FOXA2 expression. Molecular mechanism studies showed that linc00261 transcriptionally upregulates FOXA2 in cis by recruiting SMAD3. Finally, we identified EZH2 is responsible for linc00261 transcription repression via modulating trimethylation of H3K27 at Lys27 (H3K27Me3), both EZH2 and H3K27Me3 were negatively correlated with linc00261 expression in HCC. In conclusion, these findings demonstrated a crucial role of linc00261 in HCC metastasis, and that EZH2/linc00261/FOXA2 axis might reveal potential prognostic factors and be applied as therapeutic targets for HCC metastasis.
Collapse
Affiliation(s)
- Zhanjun Chen
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
- Department of General Surgery, Affiliated Baoan Hospital of Shenzhen, Southern Medical UniversityShenzhen 518101, Guangdong Province, China
| | - Leyang Xiang
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Zhigang Hu
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Huohui Ou
- Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde)Foshan 528308, Guangdong Province, China
| | - Xiao Liu
- Department of General Surgery, Foresea Life Insurance Guangzhou General HospitalGuangzhou 511356, Guangdong Province, China
| | - Lili Yu
- Cancer Research Institute, Guangdong Provincial Key Laboratory of Cancer Immunotherapy, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Wancheng Chen
- Cancer Research Institute, Guangdong Provincial Key Laboratory of Cancer Immunotherapy, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Lei Jiang
- Cancer Research Institute, Guangdong Provincial Key Laboratory of Cancer Immunotherapy, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Qiangfeng Yu
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Yinghao Fang
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Yuyan Xu
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Qin Liu
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Yu Huang
- Department of Laboratory Medicine, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Xianghong Li
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| | - Dinghua Yang
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical UniversityGuangzhou 510515, Guangdong Province, China
| |
Collapse
|
|
45
|
Lazăr AD, Dinescu S, Costache M. The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy. Cancers (Basel) 2020; 12:cancers12113378. [PMID: 33203119 PMCID: PMC7696690 DOI: 10.3390/cancers12113378] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/12/2020] [Accepted: 11/13/2020] [Indexed: 02/06/2023] Open
Abstract
Considered to be highly lethal if not diagnosed in early stages, cutaneous malignant melanoma is among the most aggressive and treatment-resistant human cancers, and its incidence continues to rise, largely due to ultraviolet radiation exposure, which is the main carcinogenic factor. Over the years, researchers have started to unveil the molecular mechanisms by which malignant melanoma can be triggered and sustained, in order to establish specific, reliable biomarkers that could aid the prognosis and diagnosis of this fatal disease, and serve as targets for development of novel efficient therapies. The high mutational burden and heterogeneous nature of melanoma shifted the main focus from the genetic landscape to epigenetic and epitranscriptomic modifications, aiming at elucidating the role of non-coding RNA molecules in the fine tuning of melanoma progression. Here we review the contribution of microRNAs and lncRNAs to melanoma invasion, metastasis and acquired drug resistance, highlighting their potential for clinical applications as biomarkers and therapeutic targets.
Collapse
Affiliation(s)
- Andreea D. Lazăr
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (A.D.L.); (M.C.)
| | - Sorina Dinescu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (A.D.L.); (M.C.)
- Research Institute of the University of Bucharest, 050663 Bucharest, Romania
- Correspondence:
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (A.D.L.); (M.C.)
- Research Institute of the University of Bucharest, 050663 Bucharest, Romania
| |
Collapse
|
|
46
|
Prognostic Value of Long Noncoding RNA SPRY4-IT1 on Survival Outcomes in Human Carcinomas: A Systematic Review and Meta-Analysis with TCGA Database. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5868602. [PMID: 33204703 PMCID: PMC7652610 DOI: 10.1155/2020/5868602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 10/16/2020] [Accepted: 10/20/2020] [Indexed: 12/27/2022]
Abstract
Background Emerging evidences have shown that long noncoding RNA SPRY4-IT1 can be aberrantly expressed in human cancers, and it could be an unfavorable prognostic factor in cancer patients. However, the prognostic mechanism of SPRY4-IT1 is still unclear. This study is aimed at evaluating its potential predictive value for cancer prognosis. Methods We thoroughly searched PubMed, Embase, Web of Science, and MEDLINE databases so as to explore the relationship between SPRY4-IT1 expression and cancer prognosis value. Then, TCGA datasets were used to validate the results of our meta-analysis. Results In all, seventeen studies involving 1650 patients were included in this meta-analysis. Pooled results showed that high expression of SPRY4-IT1 was significantly correlated with poor OS (HR = 1.96, 95% confidence interval (CI) = 1.47‐2.62, P < 0.001) in cancer patients. Furthermore, exploration of TCGA dataset further validated that SPRY4-IT1 was aberrantly expressed in various cancers, which partially confirmed our results in this meta-analysis. Conclusions The present systematic review and meta-analysis implicated that the aberrant expressions of lncRNA SPRY4-IT1 were strongly associated with clinical survival outcomes in various cancers and therefore might serve as a promising biomarker for predicting prognosis of human cancers.
Collapse
|
|
47
|
Jin Y, Zhang M, Duan R, Yang J, Yang Y, Wang J, Jiang C, Yao B, Li L, Yuan H, Zha X, Ma C. Long noncoding RNA FGF14-AS2 inhibits breast cancer metastasis by regulating the miR-370-3p/FGF14 axis. Cell Death Discov 2020; 6:103. [PMID: 33083023 PMCID: PMC7548970 DOI: 10.1038/s41420-020-00334-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 08/20/2020] [Accepted: 09/03/2020] [Indexed: 12/18/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, including breast cancer. However, the overall biological roles and clinical significance of most lncRNAs are not fully understood. This study aimed to elucidate the potential role of a novel lncRNA FGF14-AS2 and the mechanisms underlying metastasis in breast cancer. The lncRNA FGF14-AS2 was significantly downregulated in breast cancer tissues; patients with lower FGF14-AS2 expression had advanced clinical stage. In vitro and in vivo assays of FGF14-AS2 alterations revealed a complex integrated phenotype affecting breast cancer cell migration, invasion, and tumor metastasis. Mechanistically, FGF14-AS2 functioned as a competing endogenous RNA of miR-370-3p, thereby leading to the activation of its coding counterpart, FGF14. Clinically, we observed increased miR-370-3p expression in breast cancer tissues, whereas FGF14 expression was decreased in breast cancer tissues compared to the adjacent normal breast tissues. FGF14-AS2 expression was significantly negatively correlated with miR-370-3p expression, and correlated positively to FGF14 expression. Collectively, our findings support a model in which the FGF14-AS2/miR-370-3p/FGF14 axis is a critical regulator in breast cancer metastasis, suggesting a new therapeutic direction in breast cancer.
Collapse
Affiliation(s)
- Yucui Jin
- Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China.,Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| | - Ming Zhang
- Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| | - Rui Duan
- Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| | - Jiashu Yang
- Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| | - Ying Yang
- Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| | - Jue Wang
- Division of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Chaojun Jiang
- Division of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Bing Yao
- Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| | - Lingyun Li
- Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China.,Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| | - Hongyan Yuan
- Department of Oncology and Lombardi Comprehensive Cancer Center, Lombardi Comprehensive Cancer Center, Washington, DC USA
| | - Xiaoming Zha
- Division of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Changyan Ma
- Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China.,Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing, People's Republic of China
| |
Collapse
|
|
48
|
New insights into long non-coding RNAs in non-small cell lung cancer. Biomed Pharmacother 2020; 131:110775. [PMID: 33152934 DOI: 10.1016/j.biopha.2020.110775] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 09/09/2020] [Accepted: 09/17/2020] [Indexed: 12/14/2022] Open
Abstract
Lung cancer is a malignant tumor that seriously threatens human life and health. Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancer cases, and its global 5-year survival rate is only approximately 5%. Thus, the identification of new prognostic biomarkers has become one of the most urgent challenges in NSCLC research. Long noncoding RNAs (LncRNAs) are a kind of noncoding RNA whose length exceeds 200 nucleotides (nt). LncRNAs are transcribed by RNA pol II and can be subjected to posttranscriptional modifications such as blocking, polyadenylation and splicing; moreover, their expression profiles are more specific than those of mRNAs. Emerging evidence confirms that lncRNAs are associated with the occurrence and development of NSCLC and play an important role in NSCLC drug resistance. The purpose of this review was to describe the roles of lncRNAs in the development, diagnosis and prognosis of NSCLC and to explore new evidence of lncRNAs in the treatment of NSCLC drug resistance. This review provides a new perspective of lncRNAs in the treatment of NSCLC.
Collapse
|
|
49
|
Wang D, Li M, Li J, Wan X, Huang Y, Wang C, Zhang P, Xu Y, Kong Z, Lu Y, Wang X, Liu C, Ji C, Li L. Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers. DISEASE MARKERS 2020; 2020:8884450. [PMID: 33082888 PMCID: PMC7557915 DOI: 10.1155/2020/8884450] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/10/2020] [Accepted: 08/23/2020] [Indexed: 01/17/2023]
Abstract
The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data. After validating the accuracy of the array data, we constructed a transcriptional network which contained more than 30 transcriptional factors using ChIP-seq data to explore upstream regulators of androgen-responsive lncRNAs. Next, we conducted bioinformatics analysis to identify lncRNA-miRNA-mRNA regulatory network. To explore the potential roles of androgen-responsive lncRNAs in hormone-related cancers, we performed coexpression network and PPI network analyses using TCGA data. GO and KEGG analyses showed these lncRNAs were mainly involved in regulating signal transduction, transcription, development, cell adhesion, immune response, cell differentiation, and MAPK signaling pathway. We also highlight the prognostic value of HPN-AS1, TPTEP1, and LINC00623 in cancer outcomes. Our results suggest that androgen-responsive lncRNAs played important roles in regulating hormone-related cancer progression and could be novel molecular biomarkers.
Collapse
Affiliation(s)
- Dan Wang
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Mingyue Li
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510620, China
| | - Jing Li
- Department of Pathology, Zibo Central Hospital, Zibo 2550036, China
| | - Xuechao Wan
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Yan Huang
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Chenji Wang
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Pu Zhang
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Yangguang Xu
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Zhe Kong
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Yali Lu
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Xinmei Wang
- Department of Pathology, Zibo Central Hospital, Zibo 2550036, China
| | - Chuan Liu
- Department of Thyroid and Breast Surgery, Zibo Central Hospital, Zibo 255036, China
| | - Chaoneng Ji
- State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, China
| | - Liang Li
- Department of Thyroid and Breast Surgery, Zibo Central Hospital, Zibo 255036, China
| |
Collapse
|
|
50
|
He F, Huang L, Xu Q, Xiong W, Liu S, Yang H, Lu W, Xiao R, Hu Z, Cai L. Microarray profiling of differentially expressed lncRNAs and mRNAs in lung adenocarcinomas and bioinformatics analysis. Cancer Med 2020; 9:7717-7728. [PMID: 32869486 PMCID: PMC7571829 DOI: 10.1002/cam4.3369] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 06/14/2020] [Accepted: 06/27/2020] [Indexed: 12/11/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) dysregulation leads to malignant progression of lung cancer. Our study profiled differentially expressed lncRNA and mRNA in tumor and normal tissues of lung adenocarcinoma (LUAD). Further, analysis of the gene expression profiles of LUAD tissues (n = 533) and normal tissues (n = 59) from The Cancer Genome Atlas (TCGA). A total of 138 lncRNAs were differentially expressed between LUAD tissues and normal tissues (false discovery rate [FDR] q < 0.05, fold change (FC) ≥ 2), a number of which are key regulators of multiple cancer and biological processes in humans. For example, lncRNA A2M‐AS1 displayed the highest correlation with the co‐expressed mRNAs, indicating that it might play a key role in regulating differential gene expression in LUAD. The data from the current study of the comprehensive lncRNA expression profile in LUAD tissues provided useful information to guide the identification of potential LUAD biomarkers.
Collapse
Affiliation(s)
- Fei He
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.,Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Liping Huang
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.,Department of Basic Medicine, Zhangzhou Health Vocational College, Zhangzhou, China
| | - Qiuping Xu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Weimin Xiong
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Shuang Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Huimin Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Wanting Lu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China
| | - Rendong Xiao
- Department of Thoracic Surgery, The first affiliated hospital of Fujian Medical University, Fuzhou, China
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.,Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Lin Cai
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.,Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| |
Collapse
|