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1
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Khalili-Tanha G, Khalili-Tanha N, Rouzbahani AK, Mahdieh R, Jasemi K, Ghaderi R, Leylakoohi FK, Ghorbani E, Khazaei M, Hassanian SM, Gataa IS, Ferns GA, Nazari E, Avan A. Diagnostic, prognostic, and predictive biomarkers in gastric cancer: from conventional to novel biomarkers. Transl Res 2024; 274:35-48. [PMID: 39260559 DOI: 10.1016/j.trsl.2024.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 08/12/2024] [Accepted: 09/04/2024] [Indexed: 09/13/2024]
Abstract
Gastric cancer is a major health concern worldwide. The survival rate of Gastric cancer greatly depends on the stage at which it is diagnosed. Early diagnosis is critical for improving survival outcomes. To improve the chances of early diagnosis, regular screening tests, such as an upper endoscopy or barium swallow, are recommended for individuals at a higher risk due to factors like family history or a previous diagnosis of gastric conditions. Biomarkers can be detected and measured using non-invasive methods such as blood tests, urine tests, breath analysis, or imaging techniques. These non-invasive approaches offer many advantages, including convenience, safety, and cost-effectiveness, making them valuable tools for disease diagnosis, monitoring, and research. Biomarker-based tests have emerged as a useful tool for identifying gastric cancer early, monitoring treatment response, assessing the recurrence risk, and personalizing treatment plans. In this current review, we have explored both classical and novel biomarkers for gastric cancer. We have centralized their potential clinical application and discussed the challenges in Gastric cancer research.
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Affiliation(s)
- Ghazaleh Khalili-Tanha
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nima Khalili-Tanha
- Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada
| | | | - Ramisa Mahdieh
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kimia Jasemi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Rosa Ghaderi
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Elnaz Ghorbani
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Gordon A Ferns
- Brighton & Sussex Medical School, Department of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Elham Nazari
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
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2
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Lu Y, Yang B, Shen A, Yu K, Ma M, Li Y, Wang H. LncRNA UCA1 promotes vasculogenic mimicry by targeting miR-1-3p in gastric cancer. Carcinogenesis 2024; 45:658-672. [PMID: 38742453 DOI: 10.1093/carcin/bgae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 04/10/2024] [Accepted: 05/11/2024] [Indexed: 05/16/2024] Open
Abstract
Long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been implicated in several tumors. UCA1 promotes cell proliferation, migration, and invasion of gastric cancer (GC) cells, but the molecular mechanism has not been fully elucidated. This study revealed the oncogenic effects of UCA1 on cell growth and invasion. Furthermore, UCA1 expression was significantly correlated with the overall survival of GC patients, and the clinicopathological indicators, including tumor size, depth of invasion, lymph node metastasis, and TNM stage. Additionally, miR-1-3p was identified as a downstream target of UCA1, which was negatively regulated by UCA1. MiR-1-3p inhibited cell proliferation and vasculogenic mimicry (VM), and induced cell apoptosis by upregulating BAX, BAD, and tumor suppressor TP53 expression levels. Moreover, miR-1-3p almost completely reversed the oncogenic effect caused by UCA1, including cell growth, migration, and VM formation. This study also confirmed that UCA1 promoted tumor growth in vivo. In this study, we also revealed the correlation between UCA1 and VM formation, which is potentially crucial for tumor metastasis. Meanwhile, its downstream target miR-1-3p inhibited VM formation in GC cells. In summary, these findings indicate that the UCA1/miR-1-3p axis is a potential target for GC treatment.
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Affiliation(s)
- Yida Lu
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, China
| | - Bo Yang
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, China
| | - Aolin Shen
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, China
| | - Kexun Yu
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, China
| | - MengDi Ma
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, China
| | - Yongxiang Li
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, China
| | - Huizhen Wang
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei 230022, China
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3
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Yang Y, Pu J, Yang Y. Glycolysis and chemoresistance in acute myeloid leukemia. Heliyon 2024; 10:e35721. [PMID: 39170140 PMCID: PMC11336864 DOI: 10.1016/j.heliyon.2024.e35721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 08/23/2024] Open
Abstract
While traditional high-dose chemotherapy can effectively prolong the overall survival of acute myeloid leukemia (AML) patients and contribute to better prognostic outcomes, the advent of chemoresistance is a persistent challenge to effective AML management in the clinic. The therapeutic resistance is thought to emerge owing to the heterogeneous and adaptable nature of tumor cells when exposed to exogenous stimuli. Recent studies have focused on exploring metabolic changes that may afford novel opportunities to treat AML, with a particular focus on glycolytic metabolism. The Warburg effect, a hallmark of cancer, refers to metabolism of glucose through glycolysis under normoxic conditions, which contributes to the development of chemoresistance. Despite the key significance of this metabolic process in the context of malignant transformation, the underlying molecular mechanisms linking glycolysis to chemoresistance in AML remain incompletely understood. This review offers an overview of the current status of research focused on the relationship between glycolytic metabolism and AML resistance to chemotherapy, with a particular focus on the contributions of glucose transporters, key glycolytic enzymes, signaling pathways, non-coding RNAs, and the tumor microenvironment to this relationship. Together, this article will provide a foundation for the selection of novel therapeutic targets and the formulation of new approaches to treating AML.
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Affiliation(s)
- Yan Yang
- Department of Neonatology, Zigong Maternity and Child Health Care Hospital, Zigong, Sichuan, 643000, China
| | - Jianlin Pu
- Department of Psychiatry, The Zigong Affiliated Hospital of Southwest Medical University, Zigong mental health Center, Zigong Institute of Brain Science, Zigong, Sichuan, 643000, China
| | - You Yang
- Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, 646000, China
- The Second Hospital, Centre for Reproductive Medicine, Advanced Medical Research Institute, Key Laboratory for Experimental Teratology of the Ministry of Education, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China
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4
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Meng X, Bai X, Ke A, Li K, Lei Y, Ding S, Dai D. Long Non-Coding RNAs in Drug Resistance of Gastric Cancer: Complex Mechanisms and Potential Clinical Applications. Biomolecules 2024; 14:608. [PMID: 38927012 PMCID: PMC11201466 DOI: 10.3390/biom14060608] [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: 03/10/2024] [Revised: 05/11/2024] [Accepted: 05/16/2024] [Indexed: 06/28/2024] Open
Abstract
Gastric cancer (GC) ranks as the third most prevalent malignancy and a leading cause of cancer-related mortality worldwide. However, the majority of patients with GC are diagnosed at an advanced stage, highlighting the urgent need for effective perioperative and postoperative chemotherapy to prevent relapse and metastasis. The current treatment strategies have limited overall efficacy because of intrinsic or acquired drug resistance. Recent evidence suggests that dysregulated long non-coding RNAs (lncRNAs) play a significant role in mediating drug resistance in GC. Therefore, there is an imperative to explore novel molecular mechanisms underlying drug resistance in order to overcome this challenging issue. With advancements in deep transcriptome sequencing technology, lncRNAs-once considered transcriptional noise-have garnered widespread attention as potential regulators of carcinogenesis, including tumor cell proliferation, metastasis, and sensitivity to chemo- or radiotherapy through multiple regulatory mechanisms. In light of these findings, we aim to review the mechanisms by which lncRNAs contribute to drug therapy resistance in GC with the goal of providing new insights and breakthroughs toward overcoming this formidable obstacle.
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Affiliation(s)
- Xiangyu Meng
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
- Department of Gastric Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang 110042, China
| | - Xiao Bai
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Angting Ke
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Kaiqiang Li
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Yun Lei
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Siqi Ding
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Dongqiu Dai
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
- Cancer Center, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China
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5
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Ghorbani A, Hosseinie F, Khorshid Sokhangouy S, Islampanah M, Khojasteh-Leylakoohi F, Maftooh M, Nassiri M, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Nazari E, Avan A. The prognostic, diagnostic, and therapeutic impact of Long noncoding RNAs in gastric cancer. Cancer Genet 2024; 282-283:14-26. [PMID: 38157692 DOI: 10.1016/j.cancergen.2023.12.006] [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: 05/28/2023] [Revised: 11/27/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
Gastric cancer (GC), ranking as the third deadliest cancer globally, faces challenges of late diagnosis and limited treatment efficacy. Long non-coding RNAs (lncRNAs) emerge as valuable treasured targets for cancer prognosis, diagnosis, and therapy, given their high specificity, convenient non-invasive detection in body fluids, and crucial roles in diverse physiological and pathological processes. Research indicates the significant involvement of lncRNAs in various aspects of GC pathogenesis, including initiation, metastasis, and recurrence, underscoring their potential as novel diagnostic and prognostic biomarkers, as well as therapeutic targets for GC. Despite existing challenges in the clinical application of lncRNAs in GC, the evolving landscape of lncRNA molecular biology holds promise for advancing the survival and treatment outcomes of gastric cancer patients. This review provides insights into recent studies on lncRNAs in gastric cancer, elucidating their molecular mechanisms and exploring the potential clinical applications in GC.
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Affiliation(s)
- Atousa Ghorbani
- Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Hosseinie
- Department of Nursing, Faculty of Nursing and Midwifery, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Saeideh Khorshid Sokhangouy
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Muhammad Islampanah
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammadreza Nassiri
- Recombinant Proteins Research Group, The Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Nazari
- Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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6
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Shi Y, Adu-Amankwaah J, Zhao Q, Li X, Yu Q, Bushi A, Yuan J, Tan R. Long non-coding RNAs in drug resistance across the top five cancers: Update on their roles and mechanisms. Heliyon 2024; 10:e27207. [PMID: 38463803 PMCID: PMC10923722 DOI: 10.1016/j.heliyon.2024.e27207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024] Open
Abstract
Cancer drug resistance stands as a formidable obstacle in the relentless fight against the top five prevalent cancers: breast, lung, colorectal, prostate, and gastric cancers. These malignancies collectively account for a significant portion of cancer-related deaths worldwide. In recent years, long non-coding RNAs (lncRNAs) have emerged as pivotal players in the intricate landscape of cancer biology, and their roles in driving drug resistance are steadily coming to light. This comprehensive review seeks to underscore the paramount significance of lncRNAs in orchestrating resistance across a spectrum of different cancer drugs, including platinum drugs (DDP), tamoxifen, trastuzumab, 5-fluorouracil (5-FU), paclitaxel (PTX), and Androgen Deprivation Therapy (ADT) across the most prevalent types of cancer. It delves into the multifaceted mechanisms through which lncRNAs exert their influence on drug resistance, shedding light on their regulatory roles in various facets of cancer biology. A comprehensive understanding of these lncRNA-mediated mechanisms may pave the way for more effective and personalized treatment strategies, ultimately improving patient outcomes in these challenging malignancies.
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Affiliation(s)
- Yue Shi
- Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, China
| | - Joseph Adu-Amankwaah
- Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, China
| | - Qizhong Zhao
- Department of Emergency, The First Hospital of China Medical University, Shenyang, China
| | - Xin Li
- Clinical Medical College, Jining Medical University, 272067, Jining, China
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, 272067, Jining, China
| | - Qianxue Yu
- Clinical Medical College, Jining Medical University, 272067, Jining, China
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, 272067, Jining, China
| | - Aisha Bushi
- School of International Education, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Jinxiang Yuan
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, 272067, Jining, China
- Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, 272067, Jining, China
| | - Rubin Tan
- Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, China
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7
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Zhang HB, Hu Y, Deng JL, Fang GY, Zeng Y. Insights into the involvement of long non-coding RNAs in doxorubicin resistance of cancer. Front Pharmacol 2023; 14:1243934. [PMID: 37781691 PMCID: PMC10540237 DOI: 10.3389/fphar.2023.1243934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/31/2023] [Indexed: 10/03/2023] Open
Abstract
Doxorubicin is one of the most classical chemotherapeutic drugs for the treatment of cancer. However, resistance to the cytotoxic effects of doxorubicin in tumor cells remains a major obstacle. Aberrant expression of long non-coding RNAs (lncRNAs) has been associated with tumorigenesis and development via regulation of chromatin remodeling, transcription, and post-transcriptional processing. Emerging studies have also revealed that dysregulation of lncRNAs mediates the development of drug resistance through multiple molecules and pathways. In this review, we focus on the role and mechanism of lncRNAs in the progress of doxorubicin resistance in various cancers, which mainly include cellular drug transport, cell cycle disorder, anti-apoptosis, epithelial-mesenchymal transition, cancer stem cells, autophagy, tumor microenvironment, metabolic reprogramming and signaling pathways. This review is aimed to provide potential therapeutic targets for future cancer therapy, especially for the reversal of chemoresistance.
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Affiliation(s)
- Hai-Bo Zhang
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Yang Hu
- Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jun-Li Deng
- Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Guo-Ying Fang
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Ying Zeng
- Department of Pharmacy, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
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8
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Sarkar A, Paul A, Banerjee T, Maji A, Saha S, Bishayee A, Maity TK. Therapeutic advancements in targeting BCL-2 family proteins by epigenetic regulators, natural, and synthetic agents in cancer. Eur J Pharmacol 2023; 944:175588. [PMID: 36791843 DOI: 10.1016/j.ejphar.2023.175588] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 01/21/2023] [Accepted: 02/08/2023] [Indexed: 02/17/2023]
Abstract
Cancer is amongst the deadliest and most disruptive disorders, having a much higher death rate than other diseases worldwide. Human cancer rates continue to rise, thereby posing the most significant concerns for medical health professionals. In the last two decades, researchers have gone past several milestones in tackling cancer while gaining insight into the role of apoptosis in cancer or targeting various biomarker tools for prognosis and diagnosis. Apoptosis which is still a topic full of complexities, can be controlled considerably by B-cell lymphoma 2 (BCL-2) and its family members. Therefore, targeting proteins of this family to prevent tumorigenesis, is essential to focus on the pharmacological features of the anti-apoptotic and pro-apoptotic members, which will help to develop and manage this disorder. This review deals with the advancements of various epigenetic regulators to target BCL-2 family proteins, including the mechanism of several microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Similarly, a rise in natural and synthetic molecules' research over the last two decades has allowed us to acquire insights into understanding and managing the transcriptional alterations that have led to apoptosis and treating various neoplastic diseases. Furthermore, several inhibitors targeting anti-apoptotic proteins and inducers or activators targeting pro-apoptotic proteins in preclinical and clinical stages have been summarized. Overall, agonistic and antagonistic mechanisms of BCL-2 family proteins conciliated by epigenetic regulators, natural and synthetic agents have proven to be an excellent choice in developing cancer therapeutics.
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Affiliation(s)
- Arnab Sarkar
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, 700032, India.
| | - Abhik Paul
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, 700032, India.
| | - Tanmoy Banerjee
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, 700032, India.
| | - Avik Maji
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, 700032, India.
| | - Sanjukta Saha
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, 700032, India.
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA.
| | - Tapan Kumar Maity
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, 700032, India.
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9
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Li Q, Zhang H, Hu J, Zhang L, Zhao A, Feng H. Construction of anoikis-related lncRNAs risk model: Predicts prognosis and immunotherapy response for gastric adenocarcinoma patients. Front Pharmacol 2023; 14:1124262. [PMID: 36925640 PMCID: PMC10011703 DOI: 10.3389/fphar.2023.1124262] [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: 12/14/2022] [Accepted: 02/17/2023] [Indexed: 03/08/2023] Open
Abstract
Background: Anoikis acts as a programmed cell death that is activated during carcinogenesis to remove undetected cells isolated from ECM. Further anoikis based risk stratification is expected to provide a deeper understanding of stomach adenocarcinoma (STAD) carcinogenesis. Methods: The information of STAD patients were acquired from TCGA dataset. Anoikis-related genes were obtained from the Molecular Signatures Database and Pearson correlation analysis was performed to identify the anoikis-related lncRNAs (ARLs). We performed machine learning algorithms, including Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (Lasso) analyses on the ARLs to build the OS-score and OS-signature. Clinical subgroup analysis, tumor mutation burden (TMB) detection, drug susceptibility analysis, immune infiltration and pathway enrichment analysis were further performed to comprehensive explore the clinical significance. Results: We established a STAD prognostic model based on five ARLs and its prognostic value was verified. Survival analysis showed that the overall survival of high-risk score patients was significantly shorter than that of low-risk score patients. The column diagrams show satisfactory discrimination and calibration. The calibration curve verifies the good agreement between the prediction of the line graph and the actual observation. TIDE analysis and drug sensitivity analysis showed significant differences between different risk groups. Conclusion: The novel prognostic model based on anoikis-related lncRNAs we identified could be used for prognosis prediction and precise therapy in gastric adenocarcinoma.
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Affiliation(s)
- Qinglin Li
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.,Key Laboratory of Head and Neck Cancer, Translational Research of Zhejiang Province, Hangzhou, Zhejiang, China
| | | | - Jinguo Hu
- Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Lizhuo Zhang
- Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China
| | - Aiguang Zhao
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - He Feng
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.,Key Laboratory of Head and Neck Cancer, Translational Research of Zhejiang Province, Hangzhou, Zhejiang, China
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Eptaminitaki GC, Stellas D, Bonavida B, Baritaki S. Long Non-coding RNAs (lncRNAs) signaling in Cancer Chemoresistance: From Prediction to Druggability. Drug Resist Updat 2022; 65:100866. [DOI: 10.1016/j.drup.2022.100866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 11/03/2022]
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11
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Xie W, Chu M, Song G, Zuo Z, Han Z, Chen C, Li Y, Wang ZW. Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer. Semin Cancer Biol 2022; 83:303-318. [PMID: 33207266 DOI: 10.1016/j.semcancer.2020.11.004] [Citation(s) in RCA: 79] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.
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Affiliation(s)
- Wangkai Xie
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Man Chu
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China
| | - Gendi Song
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China
| | - Ziyi Zuo
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Zheng Han
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Chenbin Chen
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Yuyun Li
- Bengbu Medical College Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical College, Anhui, 233030, China.
| | - Zhi-Wei Wang
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
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12
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Parashar D, Singh A, Gupta S, Sharma A, Sharma MK, Roy KK, Chauhan SC, Kashyap VK. Emerging Roles and Potential Applications of Non-Coding RNAs in Cervical Cancer. Genes (Basel) 2022; 13:genes13071254. [PMID: 35886037 PMCID: PMC9317009 DOI: 10.3390/genes13071254] [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] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 12/06/2022] Open
Abstract
Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome's composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR-Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC.
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Affiliation(s)
- Deepak Parashar
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, MI 53226, USA
- Correspondence: (D.P.); (V.K.K.); Tel.: +1-414-439-8089 (D.P.); +1-956-296-1738 (V.K.K.)
| | - Anupam Singh
- Department of Biotechnology, GLA University, Mathura 281406, Uttar Pradesh, India; (A.S.); (S.G.)
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura 281406, Uttar Pradesh, India; (A.S.); (S.G.)
| | - Aishwarya Sharma
- Sri Siddhartha Medical College and Research Center, Tumkur 572107, Karnataka, India;
| | - Manish K. Sharma
- Department of Biotechnology, IP College, Bulandshahr 203001, Uttar Pradesh, India;
| | - Kuldeep K. Roy
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun 248007, Uttarakhand, India;
| | - Subhash C. Chauhan
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
| | - Vivek K. Kashyap
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
- South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA
- Correspondence: (D.P.); (V.K.K.); Tel.: +1-414-439-8089 (D.P.); +1-956-296-1738 (V.K.K.)
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13
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Rizk NI, Abulsoud AI, Kamal MM, Kassem DH, Hamdy NM. Exosomal-long non-coding RNAs journey in colorectal cancer: Evil and goodness faces of key players. Life Sci 2022; 292:120325. [PMID: 35031258 DOI: 10.1016/j.lfs.2022.120325] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 02/07/2023]
Abstract
Exosomes are nano-vesicles (NVs) secreted by cells and take part in cell-cell communications. Lately, these exosomes were proved to have dual faces in cancer. Actually, they can contribute to carcinogenesis through epithelial-mesenchymal transition (EMT), angiogenesis, metastasis and tumor microenvironment (TME) of various cancers, including colorectal cancer (CRC). On the other hand, they can be potential targets for cancer treatment. CRC is one of the most frequent tumors worldwide, with incidence rates rising in the recent decades. In its early stage, CRC is asymptomatic with poor treatment outcomes. Therefore, finding a non-invasive, early diagnostic biomarker tool and/or suitable defender to combat CRC is mandatory. Exosomes provide enrichment and safe setting for their cargos non-coding RNAs (ncRNAs) and proteins, whose expression levels can be upregulated ordown-regulated in cancer. Hence, exosomes can be used as diagnostic and/or prognostic tools for cancer. Moreover, exosomes can provide a novel potential therapeutic modality for tumors via loading with specific chemotherapeutic agents, with the advantage of possible tumor targeting. In this review, we will try to collect and address recent studies concerned with exosomes and their cargos' implications for CRC diagnosis and/or hopefully, treatment.
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Affiliation(s)
- Nehal I Rizk
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Ahmed I Abulsoud
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy (Boys Branch), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Mohamed M Kamal
- Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt; The Centre for Drug Research and Development, Faculty of Pharmacy, BUE, Cairo, Egypt; Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Dina H Kassem
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Nadia M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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14
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Liu Y, Ao X, Wang Y, Li X, Wang J. Long Non-Coding RNA in Gastric Cancer: Mechanisms and Clinical Implications for Drug Resistance. Front Oncol 2022; 12:841411. [PMID: 35155266 PMCID: PMC8831387 DOI: 10.3389/fonc.2022.841411] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/10/2022] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide, with high recurrence and mortality rate. Chemotherapy, including 5-fluorouracil (5-FU), adriamycin (ADR), vincristine (VCR), paclitaxel (PTX), and platinum drugs, remains one of the fundamental methods of GC treatment and has efficiently improved patients’ prognosis. However, most patients eventually develop resistance to chemotherapeutic agents, leading to the failure of clinical treatment and patients’ death. Recent studies suggest that long non-coding RNAs (lncRNAs) are involved in the drug resistance of GC by modulating the expression of drug resistance-related genes via sponging microRNAs (miRNAs). Moreover, lncRNAs also play crucial roles in GC drug resistance via a variety of mechanisms, such as the regulation of the oncogenic signaling pathways, inhibition of apoptosis, induction of autophagy, modulation of cancer stem cells (CSCs), and promotion of the epithelial-to-mesenchymal transition (EMT) process. Some of lncRNAs exhibit great potential as diagnostic and prognostic biomarkers, as well as therapeutic targets for GC patients. Therefore, understanding the role of lncRNAs and their mechanisms in GC drug resistance may provide us with novel insights for developing strategies for individual diagnosis and therapy. In this review, we summarize the recent findings on the mechanisms underlying GC drug resistance regulated by lncRNAs. We also discuss the potential clinical applications of lncRNAs as biomarkers and therapeutic targets in GC.
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Affiliation(s)
- Ying Liu
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, China
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
- *Correspondence: Ying Liu,
| | - Xiang Ao
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Yu Wang
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Xiaoge Li
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Jianxun Wang
- School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, China
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15
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Khalili-Tanha G, Moghbeli M. Long non-coding RNAs as the critical regulators of doxorubicin resistance in tumor cells. Cell Mol Biol Lett 2021; 26:39. [PMID: 34425750 PMCID: PMC8381522 DOI: 10.1186/s11658-021-00282-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 08/17/2021] [Indexed: 12/16/2022] Open
Abstract
Resistance against conventional chemotherapeutic agents is one of the main reasons for tumor relapse and poor clinical outcomes in cancer patients. Various mechanisms are associated with drug resistance, including drug efflux, cell cycle, DNA repair and apoptosis. Doxorubicin (DOX) is a widely used first-line anti-cancer drug that functions as a DNA topoisomerase II inhibitor. However, DOX resistance has emerged as a large hurdle in efficient tumor therapy. Furthermore, despite its wide clinical application, DOX is a double-edged sword: it can damage normal tissues and affect the quality of patients’ lives during and after treatment. It is essential to clarify the molecular basis of DOX resistance to support the development of novel therapeutic modalities with fewer and/or lower-impact side effects in cancer patients. Long non-coding RNAs (lncRNAs) have critical roles in the drug resistance of various tumors. In this review, we summarize the state of knowledge on all the lncRNAs associated with DOX resistance. The majority are involved in promoting DOX resistance. This review paves the way to introducing an lncRNA panel marker for the prediction of the DOX response and clinical outcomes for cancer patients.
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Affiliation(s)
- Ghazaleh Khalili-Tanha
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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16
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Yang A, Liu X, Liu P, Feng Y, Liu H, Gao S, Huo L, Han X, Wang J, Kong W. LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis. Cell Mol Biol Lett 2021; 26:33. [PMID: 34238213 PMCID: PMC8268585 DOI: 10.1186/s11658-021-00275-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 06/28/2021] [Indexed: 12/13/2022] Open
Abstract
Background Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. Methods The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. Results UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. Conclusions UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.
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Affiliation(s)
- An Yang
- Handan Central Hospital, Handan, 056001, Hebei Province, China
| | - Xin Liu
- Affiliated Hospital of Hebei University of Engineering, Handan, 056002, Hebei Province, China
| | - Ping Liu
- Handan Central Hospital, Handan, 056001, Hebei Province, China
| | - Yunzhang Feng
- Handan Central Hospital, Handan, 056001, Hebei Province, China
| | - Hongbo Liu
- Handan Central Hospital, Handan, 056001, Hebei Province, China
| | - Shen Gao
- Handan First Hospital, Handan, 056002, Hebei Province, China
| | - Limin Huo
- Handan First Hospital, Handan, 056002, Hebei Province, China
| | - Xinyan Han
- Handan Central Hospital, Handan, 056001, Hebei Province, China
| | - Jurong Wang
- Handan Central Hospital, Handan, 056001, Hebei Province, China
| | - Wei Kong
- Handan Central Hospital, Handan, 056001, Hebei Province, China.
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17
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Wu J, Xu S, Li W, Lu Y, Zhou Y, Xie M, Luo Y, Cao Y, He Y, Zeng T, Ling H. lncRNAs as Hallmarks for Individualized Treatment of Gastric Cancer. Anticancer Agents Med Chem 2021; 22:1440-1457. [PMID: 34229588 DOI: 10.2174/1871520621666210706113102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 04/16/2021] [Accepted: 04/18/2021] [Indexed: 11/22/2022]
Abstract
Gastric cancer is global cancer with a high mortality rate. A growing number of studies have found the abnormal expression of lncRNA (long noncoding RNA) in many tumors, which plays a role in promoting or inhibiting cancer. Similarly, lncRNA abnormal expression plays an essential biological function in gastric cancer. This article focuses on lncRNA involvement in the development of gastric cancer in terms of cell cycle disorder, apoptosis inhibition, metabolic remodeling, promotion of tumor inflammation, immune escape, induction of angiogenesis, and epithelial mesenchymal transition (EMT). The involvement of lncRNA in the development of gastric cancer is related to drug resistance, such as cisplatin and multi-drug resistance. It can also be used as a potential marker for the diagnosis and prognosis of gastric cancer and a target for the treatment. With an in-depth understanding of the mechanism of lncRNA in gastric cancer, new ideas for personalized treatment of gastric cancer are expected.
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Affiliation(s)
- Jing Wu
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Shan Xu
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Wei Li
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yuru Lu
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yu Zhou
- Shaoyang University, Shaoyang, Hunan 422000, China
| | - Ming Xie
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yichen Luo
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yijing Cao
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yan He
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Tiebing Zeng
- Hunan Province Cooperative innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405], Hengyang, Hunan 421001, China
| | - Hui Ling
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
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18
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Li Y, Lu L, Wu X, Li Q, Zhao Y, Du F, Chen Y, Shen J, Xiao Z, Wu Z, Hu W, Cho CH, Li M. The Multifaceted Role of Long Non-Coding RNA in Gastric Cancer: Current Status and Future Perspectives. Int J Biol Sci 2021; 17:2737-2755. [PMID: 34345204 PMCID: PMC8326121 DOI: 10.7150/ijbs.61410] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/08/2021] [Indexed: 12/22/2022] Open
Abstract
Gastric cancer (GC) is one of the major public health concerns. Long non-coding RNAs (lncRNAs) have been increasingly demonstrated to possess a strong correlation with GC and play a critical role in GC occurrence, progression, metastasis and drug resistance. Many studies have shed light on the understanding of the underlying mechanisms of lncRNAs in GC. In this review, we summarized the updated research about lncRNAs in GC, focusing on their roles in Helicobacter pylori infection, GC metastasis, tumor microenvironment regulation, drug resistance and associated signaling pathways. LncRNAs may serve as novel biomarkers for diagnosis and prognosis of GC and potential therapeutic targets. The research gaps and future directions were also discussed.
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Affiliation(s)
- Yifan Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Lan Lu
- Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province,Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, Sichuan, China
| | - Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Qianxiu Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Yu Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Zhigui Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China.,Department of Pharmacy, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Wei Hu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, Guangzhou, China
| | - Chi Hin Cho
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.,South Sichuan Institute of Translational Medicine, Luzhou 646000, Sichuan, China
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19
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LncRNA UCA1 elevates the resistance of human leukemia cells to daunorubicin by the PI3K/AKT pathway via sponging miR-613. Biosci Rep 2021; 41:228611. [PMID: 33969374 PMCID: PMC8193642 DOI: 10.1042/bsr20201389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 04/27/2021] [Accepted: 05/07/2021] [Indexed: 12/15/2022] Open
Abstract
Acute leukemia is a hematological malignant tumor. Long non-coding RNA urothelial cancer-associated 1 (UCA1) is involved in the chemo-resistance of diverse cancers, but it is unclear whether UCA1 is associated with the sensitivity of acute leukemia cells to daunorubicin (DNR). DNR (100 nM) was selected for functional analysis. The viability, cell cycle progression, apoptosis, and invasion of treated acute leukemia cells (HL-60 and U-937) were evaluated by cell counting kit-8 (CCK-8) assay, flow cytometry assay, or transwell assay. Protein levels were detected with Western blot analysis. Expression patterns of UCA1 and miR-613 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between UCA1 and microRNA-613 (miR-613) was verified by dual-luciferase reporter assay. We observed that UCA1 expression was elevated in HL-60 and U-937cells. DNR constrained viability, cell cycle progression, invasion, and facilitated apoptosis of HL-60 and U-937 cells in a dose-dependent manner, but these impacts mediated by DNR were reverted after UCA1 overexpression. MiR-613 was down-regulated in HL-60 and U-937 cells, and UCA1 was verified as a miR-613 sponge. MiR-613 inhibitor reversed DNR treatment-mediated effects on viability, cell cycle progression, apoptosis, and invasion of HL-60 and U-937 cells, but these impacts mediated by miR-613 inhibitor were counteracted after UCA1 inhibition. Notably, the inactivation of the PI3K/AKT pathway caused by DNR treatment was reversed after miR-613 inhibitor introduction, but this influence mediated by miR-613 inhibitor was offset after UCA1 knockdown. In conclusion, UCA1 up-regulation facilitated the resistance of acute leukemia cells to DNR via the PI3K/AKT pathway by sponging miR-613.
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20
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Gao Z, Wang Q, Ji M, Guo X, Li L, Su X. Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis. J Transl Med 2021; 19:229. [PMID: 34053467 PMCID: PMC8165805 DOI: 10.1186/s12967-021-02872-9] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 05/03/2021] [Indexed: 02/08/2023] Open
Abstract
Background There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression. Methods CC stem cells (CD133+CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133+CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results. Results Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133+CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133+CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice. Conclusion Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-02872-9.
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Affiliation(s)
- Zhihui Gao
- Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, Xinxiang, 453000, Henan, China
| | - Qianqing Wang
- Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, Xinxiang, 453000, Henan, China.
| | - Mei Ji
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Xiangcui Guo
- Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, Xinxiang, 453000, Henan, China
| | - Li Li
- Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, Xinxiang, 453000, Henan, China
| | - Xiaoke Su
- Department of Gynecology, Xinxiang Central Hospital, NO. 56 Jinsui Road, Xinxiang, 453000, Henan, China
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21
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Huang G, Li L, Liang C, Yu F, Teng C, Pang Y, Wei T, Song J, Wang H, Liao X, Li Y, Yang J. Upregulated UCA1 contributes to oxaliplatin resistance of hepatocellular carcinoma through inhibition of miR-138-5p and activation of AKT/mTOR signaling pathway. Pharmacol Res Perspect 2021; 9:e00720. [PMID: 33565716 PMCID: PMC7874507 DOI: 10.1002/prp2.720] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 12/24/2020] [Accepted: 01/06/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) inevitably developed oxaliplatin (OXA) resistance after long-term treatment, but the mechanism remains unclear. Here, we found that LncRNA UCA1 was upregulated in most of OXA-resistant HCC tissues and cells (HepG2/OXA and SMMC-7721/OXA). Follow-up analysis and online Kaplan-Meier Plotter revealed that HCC patients with high UCA1 level had a shorter survival compared with those with low expression. Overexpression of UCA1 increased OXA IC50 in HepG2 and SMMC-7721 cells, whereas knockdown of UCA1 decreased OXA IC50 in resistant counterparts. Moreover, dual luciferase reporter assay showed that co-transfection of UCA1-WT plasmid with miR-138-5p mimics enhanced fluorescence signals, whereas co-transfection of UCA1-Mut plasmid and miR-138-5p mimics did not induce any changes. Consistently, UCA1 levels in HepG2/OXA and SMMC-7721/OXA cells were downregulated after transfected with miR-138-5p mimics. UCA1 silencing or transfection of miR-138-5p mmics inhibited the activation of AKT and mTOR in HepG2/OXA and SMMC-7721/OXA cells, whereas UCA1 overexpression increased the phosphorylated AKT and mTOR levels in parental counterparts. Rapamycin or miR-138-5p mimics similarly suppressed the activation of AKT and mTOR, whereas UCA1 overexpression exert opposite roles. Interestingly, administration of rapamycin or miR-138-5p mimics apparently antagonized the effects of UCA1 on AKT and mTOR activation. Besides, depletion of UCA1 triggered more dramatic regression of HepG2 xenografts than that of HepG2/OXA xenografts with OXA treatment and impaired the p-AKT and p-mTOR levels in vivo. In conclusion, our findings provide the evidence that UCA1 may contribute to OXA resistance via miR-138-5p-mediated AK /mTOR activation, suggesting that UCA1 is a potential therapeutic target for HCC.
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Affiliation(s)
- Guolin Huang
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Li Li
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Chaoyong Liang
- Department of ChemotherapyAffiliated Cancer HospitalGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Fei Yu
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Cuifang Teng
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Yingxing Pang
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Tongtong Wei
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Jinjing Song
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Hanlin Wang
- Department of Internal MedicineFirst Affiliated HospitalGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Xiaoli Liao
- Department of ChemotherapyAffiliated Cancer HospitalGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Yongqiang Li
- Department of ChemotherapyAffiliated Cancer HospitalGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
| | - Jie Yang
- Department of PharmacologySchool of PharmacyGuangxi Medical UniversityNanningGuangxiPeople’s Republic of China
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22
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Li Z, Lü M, Zhou Y, Xu L, Jiang Y, Liu Y, Li X, Song M. Role of Long Non-Coding RNAs in the Chemoresistance of Gastric Cancer: A Systematic Review. Onco Targets Ther 2021; 14:503-518. [PMID: 33500626 PMCID: PMC7822221 DOI: 10.2147/ott.s294378] [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: 11/27/2020] [Accepted: 12/31/2020] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review summarises the emerging role, potential targets or pathways and regulatory mechanisms of lncRNAs involved in chemoresistance and proposes a number of clinical implications of lncRNAs as novel therapeutic targets for GC. METHODS Studies on lncRNAs involved in the chemoresistance of GC published until July 2020 in the PubMed and Web of Science databases were systematically reviewed and the expression form, role in chemoresistance, targets or pathways, corresponding drugs and potential mechanisms of relevant lncRNAs were summarised in detail. RESULTS A total of 48 studies were included in this systematic review. Amongst these studies, 32 involved single drug resistance and 16 involved in multidrug resistance (MDR). The 48 studies collected described 38 lncRNAs in the drug-resistant cells of GC, including 33 upregulated and 5 downregulated lncRNAs. Cisplatin (DDP) was the most studied drug and lncRNA MALAT1 was the most studied lncRNA related to the chemoresistance of GC. The potential mechanisms of chemoresistance for lncRNAs in GC mainly included, amongst others, reduction of apoptosis, induction of autophagy, repair of DNA damage, promotion of epithelial-mesenchymal transition (EMT) and regulation of the related signalling pathways. CONCLUSION LncRNAs play a vital role in the chemoresistance of GC and are novel therapeutic targets for the disease. Detailed chemoresistance mechanisms, translational studies and clinical trials on lncRNAs in GC are urgently needed.
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Affiliation(s)
- Zonglin Li
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Muhan Lü
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Yejiang Zhou
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Linxia Xu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Yifan Jiang
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Yi Liu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Xin Li
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Min Song
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
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23
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Heidari R, Akbariqomi M, Asgari Y, Ebrahimi D, Alinejad-Rokny H. A systematic review of long non-coding RNAs with a potential role in breast cancer. MUTATION RESEARCH. REVIEWS IN MUTATION RESEARCH 2021; 787:108375. [PMID: 34083033 DOI: 10.1016/j.mrrev.2021.108375] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 04/07/2021] [Accepted: 04/12/2021] [Indexed: 12/13/2022]
Abstract
The human transcriptome contains many non-coding RNAs (ncRNAs), which play important roles in gene regulation. Long noncoding RNAs (lncRNAs) are an important class of ncRNAs with lengths between 200 and 200,000 bases. Unlike mRNA, lncRNA lacks protein-coding features, specifically, open-reading frames, and start and stop codons. LncRNAs have been reported to play a role in the pathogenesis and progression of many cancers, including breast cancer (BC), acting as tumor suppressors or oncogenes. In this review, we systematically mined the literature to identify 65 BC-related lncRNAs. We then perform an integrative bioinformatics analysis to identify 14 lncRNAs with a potential regulatory role in BC. The biological function of these 14 lncRNAs, their regulatory mechanisms, and roles in the initiation and progression of BC are discussed in this review. Additionally, we elaborate on the current and future applications of lncRNAs as diagnostic and/or therapeutic biomarkers in BC.
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Affiliation(s)
- Reza Heidari
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Akbariqomi
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Yazdan Asgari
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Diako Ebrahimi
- Biomedical Informatics Lab, Texas Biomedical Research Institute, San Antonio, TX, 78227, United States
| | - Hamid Alinejad-Rokny
- BioMedical Machine Learning Lab (BML), The Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, NSW, 2052, Australia; Core Member of UNSW Data Science Hub, The University of New South Wales (UNSW Sydney), Sydney, NSW, 2052, Australia; Health Data Analytics Program Leader, AI-enabled Processes (AIP) Research Centre, Macquarie University, Sydney, 2109, Australia.
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24
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Non-coding RNAs underlying chemoresistance in gastric cancer. Cell Oncol (Dordr) 2020; 43:961-988. [PMID: 32495294 DOI: 10.1007/s13402-020-00528-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 04/17/2020] [Accepted: 04/24/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is a major health issue in the Western world. Current clinical imperatives for this disease include the identification of more effective biomarkers to detect GC at early stages and enhance the prevention and treatment of metastatic and chemoresistant GC. The advent of non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long-non coding RNAs (lncRNAs), has led to a better understanding of the mechanisms by which GC cells acquire features of therapy resistance. ncRNAs play critical roles in normal physiology, but their dysregulation has been detected in a variety of cancers, including GC. A subset of ncRNAs is GC-specific, implying their potential application as biomarkers and/or therapeutic targets. Hence, evaluating the specific functions of ncRNAs will help to expand novel treatment options for GC. CONCLUSIONS In this review, we summarize some of the well-known ncRNAs that play a role in the development and progression of GC. We also review the application of such ncRNAs in clinical diagnostics and trials as potential biomarkers. Obviously, a deeper understanding of the biology and function of ncRNAs underlying chemoresistance can broaden horizons toward the development of personalized therapy against GC.
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25
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Li P, Wang L, Li P, Hu F, Cao Y, Tang D, Ye G, Li H, Wang D. Silencing lncRNA XIST exhibits antiproliferative and proapoptotic effects on gastric cancer cells by up-regulating microRNA-132 and down-regulating PXN. Aging (Albany NY) 2020; 13:14469-14481. [PMID: 33154189 PMCID: PMC8202840 DOI: 10.18632/aging.103635] [Citation(s) in RCA: 9] [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: 10/11/2019] [Accepted: 06/25/2020] [Indexed: 02/07/2023]
Abstract
The present study aims to elucidate the potential therapeutic role of lncRNA XIST in gastric cancer through regulation of microRNA-132 (miR-132) and paxillin (PXN) expression. The study employed 65 gastric cancer tissue specimens and SGC7901 cell lines. Our results demonstrated that expression of lncRNA XIST and PXN was significantly elevated while the expression of miR-132 was significantly reduced in gastric cancer tissues. Dual-luciferase, RNA pull-down and RIP assays demonstrated that lncRNA XIST up-regulated the PXN expression by competitively binding to miR-132. Moreover, silencing of lncRNA XIST and up-regulation of miR-132 could suppress tumor formation ability, cell proliferation and migration, but enhanced apoptosis in gastric cancer. However, the overexpression of PXN achieved the opposite tumor-promotive effect. Meanwhile, rescue experiments suggested that silencing of lncRNA XIST could reverse the tumor-promotive effect exerted by either miR-132 inhibitor or PXN. Taken together, the present study demonstrates lncRNA XIST as a novel oncogenic lncRNA in gastric cancer, highlighting its therapeutic role in this disease.
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Affiliation(s)
- Ping Li
- Department of General Surgery, Huaian Tumor Hospital, Huaian Hospital of Huaian City, Huaian, 223200, P.R. China
- Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University, Mannheim 68167, Germany
| | - Liuhua Wang
- Department of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Institute of General Surgery - Yangzhou, Yangzhou University, Yangzhou 225000, P.R. China
| | - Pengfei Li
- Department of General Surgery, Huaian Tumor Hospital, Huaian Hospital of Huaian City, Huaian, 223200, P.R. China
| | - Fangyong Hu
- Department of General Surgery, Huaian Tumor Hospital, Huaian Hospital of Huaian City, Huaian, 223200, P.R. China
| | - Yi Cao
- Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University, Mannheim 68167, Germany
| | - Dong Tang
- Department of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Institute of General Surgery - Yangzhou, Yangzhou University, Yangzhou 225000, P.R. China
| | - Gang Ye
- Department of General Surgery, Jiangdu People's Hospital of Yangzhou, Yangzhou 225200, P.R. China
| | - Hongbo Li
- Department of General Surgery, Jiangdu People's Hospital of Yangzhou, Yangzhou 225200, P.R. China
| | - Daorong Wang
- Department of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Institute of General Surgery - Yangzhou, Yangzhou University, Yangzhou 225000, P.R. China
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26
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Singh D, Khan MA, Siddique HR. Emerging role of long non-coding RNAs in cancer chemoresistance: unravelling the multifaceted role and prospective therapeutic targeting. Mol Biol Rep 2020; 47:5569-5585. [PMID: 32601922 DOI: 10.1007/s11033-020-05609-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 06/20/2020] [Indexed: 12/11/2022]
Abstract
Chemotherapy is one of the important treatment modules in early as well as advanced stages of cancer. However, the major limitation of chemotherapy is the development of chemoresistance in the transformed cells of cancer patients, which leads to cancer recurrence. Long non-coding RNAs (lncRNA) are the transcripts longer than 200 nucleotides in length, which are reported to associate with the initiation, progression, recurrence, and metastasis of different cancers. Several lncRNAs have been implicated in the prevalence of chemoresistant phenotypes and also in the restoration of drug sensitivity in chemoresistant cells. LncRNAs such as HOTAIR, H19, and a lot more are involved in the chemoresistance of cancer cells. Therefore, targeting the lncRNAs may serve as a novel strategy for treating chemoresistant cancer. This review throws light on the role of lncRNA in chemoresistance along with the perspective of the therapeutic targets for the treatment of multiple cancers.
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Affiliation(s)
- Deepti Singh
- Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, 202002, India
| | - Mohammad Afsar Khan
- Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, 202002, India
| | - Hifzur R Siddique
- Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, 202002, India.
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27
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Qu Y, Tan HY, Chan YT, Jiang H, Wang N, Wang D. The functional role of long noncoding RNA in resistance to anticancer treatment. Ther Adv Med Oncol 2020; 12:1758835920927850. [PMID: 32536982 PMCID: PMC7268113 DOI: 10.1177/1758835920927850] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 04/28/2020] [Indexed: 12/12/2022] Open
Abstract
Chemotherapy is one of the fundamental methods of cancer treatment. However, drug resistance remains the main cause of clinical treatment failure. We comprehensively review the newly identified roles of long noncoding RNAs (lncRNAs) in oncobiology that are associated with drug resistance. The expression of lncRNAs is tissue-specific and often dysregulated in human cancers. Accumulating evidence suggests that lncRNAs are involved in chemoresistance of cancer cells. The main lncRNA-driven mechanisms of chemoresistance include regulation of drug efflux, DNA damage repair, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT), induction of signaling pathways, and angiogenesis. LncRNA-driven mechanisms of resistance to various antineoplastic agents have been studied extensively. There are unique mechanisms of resistance against different types of drugs, and each mechanism may have more than one contributing factor. We summarize the emerging strategies that can be used to overcome the technical challenges in studying and addressing lncRNA-mediated drug resistance.
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Affiliation(s)
- Yidi Qu
- School of Life Sciences, Jilin University, Changchun, China
| | - Hor-Yue Tan
- School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., P.R. China
| | - Yau-Tuen Chan
- School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., P.R. China
| | - Hongbo Jiang
- School of Life Sciences, Jilin University, Changchun, China
| | - Ning Wang
- School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., P.R. China
| | - Di Wang
- School of Life Sciences, Jilin University, Changchun, 130012, China
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28
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Yuan L, Xu ZY, Ruan SM, Mo S, Qin JJ, Cheng XD. Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance. Mol Cancer 2020; 19:96. [PMID: 32460771 PMCID: PMC7251695 DOI: 10.1186/s12943-020-01219-0] [Citation(s) in RCA: 224] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 05/21/2020] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate of patients with early-stage localized gastric cancer is more than 60%, whereas that of patients with distant metastasis is less than 5%. Surgical resection is the best option for early-stage gastric cancer, while chemotherapy is mainly used in the middle and advanced stages of this disease, despite the frequently reported treatment failure due to chemotherapy resistance. Therefore, there is an unmet medical need for identifying new biomarkers for the early diagnosis and proper management of patients, to achieve the best response to treatment. Long non-coding RNAs (lncRNAs) in body fluids have attracted widespread attention as biomarkers for early screening, diagnosis, treatment, prognosis, and responses to drugs due to the high specificity and sensitivity. In the present review, we focus on the clinical potential of lncRNAs as biomarkers in liquid biopsies in the diagnosis and prognosis of gastric cancer. We also comprehensively discuss the roles of lncRNAs and their molecular mechanisms in gastric cancer chemoresistance as well as their potential as therapeutic targets for gastric cancer precision medicine.
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Affiliation(s)
- Li Yuan
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China
| | - Zhi-Yuan Xu
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Banshan Road 1#, Gongshu District, Hangzhou, 310022 China
| | - Shan-Ming Ruan
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China
| | - Shaowei Mo
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 China
| | - Jiang-Jiang Qin
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Banshan Road 1#, Gongshu District, Hangzhou, 310022 China
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, 310053 China
| | - Xiang-Dong Cheng
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Banshan Road 1#, Gongshu District, Hangzhou, 310022 China
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29
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Wang W, Liu G, Liu M, Li X. Long non-coding RNA SNHG7 promotes malignant melanoma progression through negative modulation of miR-9. Histol Histopathol 2020; 35:973-981. [PMID: 32365219 DOI: 10.14670/hh-18-225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Long non-coding small nucleolar RNA host gene 7 (lncRNA SNHG7) was verified to act as an onco-gene in human cancers. Nevertheless, the role of SNHG7 in malignant melanoma remains elusive. The present study showed an increase of SNHG7 expression in malignant melanoma tissues and cell lines. Besides, SNHG7 knockdown inhibited proliferation and migration in malignant melanoma cells. Bioinformatics analysis demonstrated that SNHG7 functions as a molecular sponge for miR-9 in biological behavior of melanoma cells. And miR-9 could inhibit the expression of PI3KR3 by binding with the 3'-UTR. Furthermore, PI3KR3, pAKT, cyclin D1 and Girdin expression was down-regulated after SNHG7 knockdown by siRNA. In addition, SNHG7 knockdown decreased xenograft growth in vivo. Taken together, this research demonstrated that SNHG7 was an oncogene in malignant melanoma, providing a novel insight for the pathogenesis and new potential therapeutic target for malignant melanoma.
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Affiliation(s)
- Wendi Wang
- Department of Plastic and Burn Surgery, Tianjin First Center Hospital, Tianjin, China
| | - Guangjing Liu
- Department of Plastic and Burn Surgery, Tianjin First Center Hospital, Tianjin, China
| | - Man Liu
- Department of Plastic and Burn Surgery, Tianjin First Center Hospital, Tianjin, China
| | - Xiaobing Li
- Department of Plastic and Burn Surgery, Tianjin First Center Hospital, Tianjin, China.
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30
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Jiang W, Xia J, Xie S, Zou R, Pan S, Wang ZW, Assaraf YG, Zhu X. Long non-coding RNAs as a determinant of cancer drug resistance: Towards the overcoming of chemoresistance via modulation of lncRNAs. Drug Resist Updat 2020; 50:100683. [DOI: 10.1016/j.drup.2020.100683] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 02/18/2020] [Accepted: 02/21/2020] [Indexed: 12/11/2022]
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31
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Fattahi S, Kosari-Monfared M, Golpour M, Emami Z, Ghasemiyan M, Nouri M, Akhavan-Niaki H. LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine. J Cell Physiol 2020; 235:3189-3206. [PMID: 31595495 DOI: 10.1002/jcp.29260] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 09/03/2019] [Indexed: 02/06/2023]
Abstract
Gastric cancer is the third leading cause of cancer death with 5-year survival rate of about 30-35%. Since early detection is associated with decreased mortality, identification of novel biomarkers for early diagnosis and proper management of patients with the best response to therapy is urgently needed. Long noncoding RNAs (lncRNAs) due to their high specificity, easy accessibility in a noninvasive manner, as well as their aberrant expression under different pathological and physiological conditions, have received a great attention as potential diagnostic, prognostic, or predictive biomarkers. They may also serve as targets for treating gastric cancer. In this review, we highlighted the role of lncRNAs as tumor suppressors or oncogenes that make them potential biomarkers for the diagnosis and prognosis of gastric cancer. Relatively, lncRNAs such as H19, HOTAIR, UCA1, PVT1, tissue differentiation-inducing nonprotein coding, and LINC00152 could be potential diagnostic and prognostic markers in patients with gastric cancer. Also, the impact of lncRNAs such as ecCEBPA, MLK7-AS1, TUG1, HOXA11-AS, GAPLINC, LEIGC, multidrug resistance-related and upregulated lncRNA, PVT1 on gastric cancer epigenetic and drug resistance as well as their potential as therapeutic targets for personalized medicine was discussed.
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Affiliation(s)
- Sadegh Fattahi
- Department of Genetics, Student Research Committee, Babol University of Medical Sciences, Babol, Iran
- Department of Genetics, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
- Department of Biochemistry, North Research Center, Pasteur Institute, Amol, Iran
| | | | - Monireh Golpour
- Department of Immunology, Molecular and Cell Biology Research Center, Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zakieh Emami
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Ghasemiyan
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Nouri
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Haleh Akhavan-Niaki
- Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
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32
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Wei L, Sun J, Zhang N, Zheng Y, Wang X, Lv L, Liu J, Xu Y, Shen Y, Yang M. Noncoding RNAs in gastric cancer: implications for drug resistance. Mol Cancer 2020; 19:62. [PMID: 32192494 PMCID: PMC7081551 DOI: 10.1186/s12943-020-01185-7] [Citation(s) in RCA: 331] [Impact Index Per Article: 66.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 03/12/2020] [Indexed: 12/18/2022] Open
Abstract
Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.
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Affiliation(s)
- Ling Wei
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Jujie Sun
- Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Nasha Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Yan Zheng
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Xingwu Wang
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Liyan Lv
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Jiandong Liu
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Yeyang Xu
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Yue Shen
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China
| | - Ming Yang
- Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China.
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Silence of FAM83H-AS1 promotes chemosensitivity of gastric cancer through Wnt/β-catenin signaling pathway. Biomed Pharmacother 2020; 125:109961. [PMID: 32028241 DOI: 10.1016/j.biopha.2020.109961] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 01/18/2020] [Accepted: 01/23/2020] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) is a malignant tumor originated from the epithelium of gastric mucosa, its incidence is second only to lung cancer in China. Chemotherapy is one of the most effective methods to treat GC, but some patients are insensitive to chemotherapeutic drugs, leading to chemotherapy failure. In this study, the expression of FAM83H-AS1 was up-regulated in GC tissues and cell lines, and was related to differentiation, invasion depth and chemotherapy insensitivity of GC patients. FAM83H-AS1 was high-expressed in chemoresistant GC tissues and cell line (SGC7901/R), and silence of FAM83H-AS1 sensitized SGC7901/R cells to cisplatin (CDDP) and 5-fluorouracil (5-FU). In addition, silence of FAM83H-AS1 could inactivate Wnt/β-catenin signaling pathway in SGC7901/R cells. The activating of Wnt/β-catenin signaling pathway reversed the promoting effect of FAM83H-AS1 silence on chemotherapy sensitivity, which meant Wnt/β-catenin signaling pathway mediated the regulation of FAM83H-AS1 on chemotherapy sensitivity in SGC7901/R cells. In conclusion, FAM83H-AS1 is related with the CDDP and 5-FU insensitivity of GC patients, silence of FAM83H-AS1 promotes chemosensitivity of GC through Wnt/β-catenin signaling pathway.
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Ghafouri-Fard S, Taheri M. Long non-coding RNA signature in gastric cancer. Exp Mol Pathol 2019; 113:104365. [PMID: 31899194 DOI: 10.1016/j.yexmp.2019.104365] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 12/18/2019] [Accepted: 12/28/2019] [Indexed: 02/07/2023]
Abstract
Gastric cancer as a common human malignancy has been associated with aberrant expressions of several coding and non-coding genes. Long non-coding RNAs (lncRNAs) as regulators of gene expressions at different genomic, transcriptomic and post-transcriptomic levels are among putative biomarkers and therapeutic targets in gastric cancer. In the present study, we have searched available literature and listed lncRNAs that are involved in the pathogenesis of gastric cancer. In addition, we discuss associations between expressions of these lncRNAs and tumoral features or risk factors for gastric cancer. Based on the established role of lncRNAs in regulation of genomic stability, cell cycle, apoptosis, angiogenesis and other aspects of cell physiology, the potential of these transcripts as therapeutic targets in gastric cancer should be evaluated in future studies.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of prostate cancer by sponging miR-4739 to upregulate MEF2D. Biomed Pharmacother 2019; 122:109557. [PMID: 31918265 DOI: 10.1016/j.biopha.2019.109557] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 10/15/2019] [Accepted: 10/17/2019] [Indexed: 02/07/2023] Open
Abstract
Prostate cancer (PCa) is a destructive malignancy with a bad prognosis. LncRNA VPS9D1-AS1 has recently been delineated as an oncogene in some kinds of tumor, whereas, the function of VPS9D1-AS1 in PCa remains to be clarified. In this study, we researched its underlying role in PCa. The expression of VPS9D1-AS1 was conspicuously upregulated in PCa tissues and cells. And absence of VPS9D1-AS1 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in PCa. In addition, VPS9D1-AS1 overexpression led to opposite results. Furthermore, VPS9D1-AS1/MEF2D could sponge with miR-4739. VPS9D1-AS1/MEF2D and miR-4739 were inversely correlated in tumor cells. And the expression of miR-4739 is markedly downregulated in PCa, meanwhile, that of MEF2D exhibited the opposite tendency. However, MEF2D was positively regulated by VPS9D1-AS1. Moreover, MEF2D upregulation offset the suppressive effects of VPS9D1-AS1 deficiency on cell proliferation, migration and invasion in PCa. Additionally, ZEB1 contained the binding sites of VPS9D1-AS1 promoter, and there existed positive relation between them. Taken together, above results illustrated that ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of PCa by sponging miR-4739 to upregulate MEF2D, which offering a new useful reference for studying the development process of PCa.
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Shi FT, Chen LD, Zhang LF. Long Noncoding RNA UCA1 Overexpression Is Associated with Poor Prognosis in Digestive System Malignancies: A Meta-analysis. Curr Med Sci 2019; 39:694-701. [PMID: 31612385 DOI: 10.1007/s11596-019-2094-3] [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: 05/09/2019] [Revised: 09/03/2019] [Indexed: 10/25/2022]
Abstract
Long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) has been reported to be highly expressed in many kinds of cancers. This meta-analysis summarized its potential prognostic value in digestive system malignancies. A meta-analysis was performed through a comprehensive search in PubMed, EMBASE, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) for suitable articles on the prognostic impact of UCA1 in digestive system malignancies from inception to June 27, 2019. Pooled hazard ratios (HRs) with 95% confidence interval (95%CI) were calculated to summarize the effect. Sixteen studies were included in the study, with a total of 1504 patients. A significant association was observed between UCA1 abundance and poor overall survival (OS), and shorter disease-free survival (DFS) for patients with digestive system malignancies, with pooled HR of 2.07 (95%CI: 1.74-2.47), and of 2.50 (95%CI: 1.62-3.86). Subgroup analysis and sensitivity analysis suggested the reliability of our findings. It is suggested that UCA1 abundance may serve as a reliable predictive factor for poor prognosis in patients with digestive system malignancies.
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Affiliation(s)
- Fei-Tao Shi
- Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Li-Dong Chen
- Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Lian-Feng Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
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The long non-coding RNA, urothelial carcinoma associated 1, promotes cell growth, invasion, migration, and chemo-resistance in glioma through Wnt/β-catenin signaling pathway. Aging (Albany NY) 2019; 11:8239-8253. [PMID: 31596734 PMCID: PMC6814589 DOI: 10.18632/aging.102317] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 09/21/2019] [Indexed: 02/07/2023]
Abstract
The long non-coding RNA, urothelial carcinoma associated 1 (UCA1) has been demonstrated to play important roles in various types of cancers. This study investigated the functional role of UCA1 in glioma and explored the underlying molecular mechanisms. UCA1 was found to be highly up-regulated in glioma cells, and knock-down of UCA1 inhibited cell growth, invasion and migration, and also induced apoptosis in glioma cells. On the other hand, overexpression of UCA1 promoted cell proliferation, cell invasion and migration in glioma cells. Knock-down of UCA1 suppressed the activity of Wnt/β-catenin signaling, and treatment with lithium chloride restored the inhibitory effect of UCA1 knock-down on cell invasion and migration. More importantly, the aberrant expression of UCA1 was associated with chemo-resistance to cisplatin and temozolomide in glioma cells via interacting with Wnt/β-catenin signaling. In vivo studies showed that overexpression of UCA1 promoted the in vivo tumor growth of U87 cells in the nude mice. Clinically, UCA1 was found to be up-regulated in glioma tissues and higher expression level of UCA1 was correlated with poor survival in patients with glioma. Taken together, our results showed that UCA1 had a functional role in the regulation of glioma cell growth, invasion and migration, and chemo-resistance possibly via Wnt/β-catenin signaling pathway.
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Xu R, Han Y. Long non-coding RNA FOXF1 adjacent non-coding developmental regulatory RNA inhibits growth and chemotherapy resistance in non-small cell lung cancer. Arch Med Sci 2019; 15:1539-1546. [PMID: 31749883 PMCID: PMC6855145 DOI: 10.5114/aoms.2019.86707] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 07/04/2017] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Lung cancer is one of the most common malignant neoplasms around the globe. Its most common type is non-small cell lung cancer (NSCLC). The FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) gene is an lncRNA which has been reported to show low expression and a tumor suppressor role in NSCLC. MATERIAL AND METHODS The expression of FENDRR in NSCLC patients' tissues and cell line was detected by quantitative real-time PCR. MTT assay was used to detect cell proliferation and chemotherapy resistance. Cell apoptosis was measured by flow cytometry. RESULTS The expression of FENDRR was low in NSCLC tissues and cells in contrast to control tissues and cells, and low FENDRR expression correlated with high TNM stages and poor differentiation of NSCLC, and could be a promising prognostic factor for NSCLC. FENDRR enhancement could inhibit the proliferation ability and advance cell apoptosis of A549 cells. The expression of FENDRR in NSCLC tissues and cells insensitive to cisplatin was much lower than that in NSCLC tissues and cells sensitive to cisplatin. The chemotherapy resistance to cisplatin of A549/DDP cells was depressed by FENDRR enhancement, and IC50 for cisplatin presented a conspicuous depression. FENDRR up-regulation inhibited cell viability of A549/DDP cells under treatment with 5 µg/ml DDP. TCGA Pan-Cancer (PANCAN) showed that the expression of FENDRR was negatively correlated with the expression of ABCC10 in lung cancer, and our western blot found that FENDRR up-regulation inhibited the expression of ABCC10 in A549/DDP cells. CONCLUSIONS LncRNA FENDRR has low expression in NSCLC and functions as a potential tumor-suppressing gene to inhibit growth and chemotherapy resistance of NSCLC cells.
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Affiliation(s)
- Ran Xu
- Department of Thoracic Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
| | - Yun Han
- Department of Thoracic Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
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Zhang L, Zheng C, Sun Z, Wang H, Wang F. Long non-coding RNA urothelial cancer associated 1 can regulate the migration and invasion of colorectal cancer cells (SW480) via myocardin-related transcription factor-A. Oncol Lett 2019; 18:4185-4193. [PMID: 31579420 PMCID: PMC6757313 DOI: 10.3892/ol.2019.10737] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 07/03/2019] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-associated mortalities. Long non-coding RNAs (lncRNAs) have been identified as key regulators in the occurrence and development of CRC. The lncRNA urothelial cancer associated 1 (UCA1) has been demonstrated to promote the development of numerous different types of cancer. In the present study, a novel molecular mechanism of UCA1, regulating the migratory and invasive capabilities of SW480 CRC cells was identified. UCA1 promoted the migration and invasion of SW480 cells by suppressing phosphorylation of myocardin-related transcription factor-A (MRTF-A). Our findings indicated that UCA1 competes with extracellular signal-regulated kinases1/2 to inhibit the phosphorylation of MRTF-A. These novel discoveries may reveal additional functions of UCA1, which may support future clinical development of novel drug targets.
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Affiliation(s)
- Long Zhang
- Cancer Diagnosis and Treatment Center, Nankai University People's Hospital, Tianjin 300071, P.R. China
| | - Chengcheng Zheng
- Cancer Diagnosis and Treatment Center, Nankai University People's Hospital, Tianjin 300071, P.R. China
| | - Zhen Sun
- Cancer Diagnosis and Treatment Center, Nankai University People's Hospital, Tianjin 300071, P.R. China
| | - Huaqing Wang
- Cancer Diagnosis and Treatment Center, Nankai University People's Hospital, Tianjin 300071, P.R. China
| | - Fengwei Wang
- Cancer Diagnosis and Treatment Center, Nankai University People's Hospital, Tianjin 300071, P.R. China
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Downregulation of lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease through the inhibition of the PI3K/Akt signaling pathway. Int Immunopharmacol 2019; 75:105734. [PMID: 31301558 DOI: 10.1016/j.intimp.2019.105734] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 06/21/2019] [Accepted: 06/29/2019] [Indexed: 01/05/2023]
Abstract
This study is conducted to investigate the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in the protection of dopaminergic neurons in Parkinson's disease (PD) through regulating the PI3K/Akt signaling pathway. PD rat model was induced by injection of 6-hydroxydopamine (6-OHDA) to damage the substantia nigra striatum. The successfully modeled PD rats were introduced with siRNA-negative control (NC) or UCA1-siRNA. The expression of UCA1 in neurobehavioral change, neuroinflammatory response and oxidative stress of PD rats were explored. The effect of UCA1 on the PI3K/Akt signaling pathway and downstream proteins IκBα and ERK was also investigated. The rats with PD exhibited aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress. Down-regulation of UCA1 up-regulated the expression of TH positive cells and DA content, reduced the apoptosis of substantia nigra neurons, the apoptosis of substantia nigra neurons and oxidative stress and improved the neuroinflammatory response in PD rats. Down-regulation of UCA1 inhibited the activation of the PI3K/AKT signaling pathway in substantia nigra of PD rats. Our study suggests that the downregulated lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in PD rats through the inhibition of the PI3K/Akt signaling pathway.
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UCA1 long non-coding RNA: An update on its roles in malignant behavior of cancers. Biomed Pharmacother 2019; 120:109459. [PMID: 31585301 DOI: 10.1016/j.biopha.2019.109459] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 09/06/2019] [Accepted: 09/12/2019] [Indexed: 12/24/2022] Open
Abstract
The lncRNA urothelial carcinoma-associated 1 (UCA1) is a 1.4 kb long transcript which has been firstly recognized in human bladder cancer cell line. Subsequent studies revealed its over-expression in a wide array of human cancer cell lines and patients' samples. In addition to conferring malignant phenotype to cells, it enhances resistance to conventional anti-cancer drugs. Moreover, transcript levels of this lncRNA have been regarded as diagnostic markers in several cancer types including gastric, bladder and liver cancers. The underlying mechanism of its participation in carcinogenesis has been identified in some cancer types. Sponging tumor suppressor miRNAs, interacting with cancer-promoting signaling pathways and enhancing cell cycle progression are among these mechanisms. Although few studies have shown anti-carcinogenic properties for this lncRNA, the bulk of evidence supports its oncogenic roles. In the current study, we have reviewed the current literature on the role of UCA1 in the carcinogenic process based on the results of in vitro studies, investigations in animal models and assessment of UCA1 expression in clinical samples.
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Long noncoding RNA X-inactive specific transcript promotes malignant melanoma progression and oxaliplatin resistance. Melanoma Res 2019; 29:254-262. [PMID: 30640294 DOI: 10.1097/cmr.0000000000000560] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Long noncoding RNA X-inactive specific transcript (XIST) was confirmed to participate in the development of many cancers. However, the function of XIST in malignant melanoma (MM) remained largely unknown. In the current study, we found that the XIST expression level was upregulated in MM tissues and cell lines. In addition, the growth rate of MM cells transfected with silencing XIST was significantly decreased compared with that with silencing normal control. XIST knockdown inhibited proliferation and migration in MM cells and increased the oxaliplatin sensitivity of oxaliplatin-resistant MM cells. Bioinformatics analysis showed that XIST acts as a molecular sponge for miR-21 and miR-21 directly targets with 3'-UTR of PI3KR1. Furthermore, XIST knockdown inhibited PI3KRI and AKT expression, and promoted Bcl-2 and Bax expression. In short, the current study showed that XIST was a crucial regulator in progression and oxaliplatin resistance of MM, providing a novel insight into the pathogenesis and underlying therapeutic target for MM.
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Li Y, Zhu G, Ma Y, Qu H. lncRNA CCAT1 contributes to the growth and invasion of gastric cancer via targeting miR-219-1. J Cell Biochem 2019; 120:19457-19468. [PMID: 31478245 DOI: 10.1002/jcb.29239] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 12/05/2017] [Indexed: 01/17/2023]
Abstract
Gastric cancer (GC) is one of the most malignant tumors that seriously threaten human health. Increased reports have indicated that long noncoding RNAs (lncRNAs) are associated with GC. This study aims to investigate the regulatory role of colon cancer-associated transcript-1 (CCAT1) in GC. The results exhibited the fact that CCAT1 was expressed higher in 57 GC tissue samples than in 57 paired adjacent normal tissue samples. The expression of CCAT1 was also increased in GC cell lines (MKN45, Hs746T, and SGC-7901) compared with the gastric epithelial cell line GES-1. Besides this, decreased cell proliferation with increased cell apoptosis was detected in SGC-7902 cells transfected with CCAT1 short hairpin RNA (shRNA). At the same time, a lower cell invasion ability was measured in SCG-7901 cells transfected with CCAT1 shRNA.In addition, miR-219-1 was predicted and convinced a direct target of CCAT1. The expression of miR-219-1 was decreased in GC tissues and GC cell lines. Further studies demonstrated that the roles of CCAT1 in cell proliferation, apoptosis, and invasion were inhibited by miR-219-1. Finally, in vivo experiment indicated that tumor growth of GC was suppressed through knockdown of CCAT1. In conclusion, these results suggested that CAT1 promotes the tumorigenesis and progression of GC by negatively regulating miR-219-1.
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Affiliation(s)
- Yanfeng Li
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Guanyu Zhu
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yan Ma
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Hongyan Qu
- Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Chen F, Li Z, Deng C, Yan H. Integration analysis for novel lncRNA markers predicting tumor recurrence in human colon adenocarcinoma. J Transl Med 2019; 17:299. [PMID: 31470869 PMCID: PMC6717325 DOI: 10.1186/s12967-019-2049-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 08/25/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Numerous evidence has suggested that long non-coding RNA (lncRNA) acts an important role in tumor biology. This study focuses on the identification of novel prognostic lncRNA biomarkers predicting tumor recurrence in human colon adenocarcinoma. METHODS We obtained the research data from The Cancer Genome Atlas (TCGA) database. The interaction among different expressed lncRNA, miRNA and mRNA markers between colon adenocarcinoma patients with and without tumor recurrence were verified with miRcode, starBase and miRTarBase databases. We established the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network based on the verified association between the selected markers. We performed the functional enrichment analysis to obtain better understanding of the selected lncRNAs. Then we use multivariate logistic regression to identify the prognostic lncRNA markers with covariates. We also generated a nomogram predicting tumor recurrence risk based on the identified lncRNA biomarkers and clinical covariates. RESULTS We included 12,727 lncRNA, 1881 miRNA and 47,761 mRNA profiling and clinical features for 113 colon adenocarcinoma patients obtained from the TCGA database. After filtration, we used 37 specific lncRNAs, 60 miRNAs and 148 mRNAs in the ceRNA network analysis. We identified five lncRNAs as prognostic lncRNA markers predicting tumor recurrence in colon adenocarcinoma, in which four of them were identified for the first time. Finally, we generated a nomogram illustrating the association between the identified lncRNAs and the tumor recurrence risk in colon adenocarcinoma. CONCLUSIONS The four newly identified lncRNA biomarkers might be potential prognostic biomarkers predicting tumor recurrence in colon adenocarcinoma. We recommend that further clinical and fundamental researches be conducted on the identified lncRNA markers.
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Affiliation(s)
- Fangyao Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, 76 Yanta Xilu Road, Xi’an, 710061 Shaanxi China
| | - Zhe Li
- First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta Xilu Road, Xi’an, 710061 Shaanxi China
| | - Changyu Deng
- Department of Preventive Medicine, Shantou University Medical College, 22 Xinling Road, Jinping District, Shantou, 515041 Guangdong China
| | - Hong Yan
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, 76 Yanta Xilu Road, Xi’an, 710061 Shaanxi China
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Wang CJ, Zhu CC, Xu J, Wang M, Zhao WY, Liu Q, Zhao G, Zhang ZZ. The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer 2019; 18:115. [PMID: 31272462 PMCID: PMC6609402 DOI: 10.1186/s12943-019-1032-0] [Citation(s) in RCA: 186] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 05/22/2019] [Indexed: 12/21/2022] Open
Abstract
Background UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear. Methods We collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells’ migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo. Results UCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, −26b, −193a and − 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model. Conclusions UCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment. Electronic supplementary material The online version of this article (10.1186/s12943-019-1032-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chao-Jie Wang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Chun-Chao Zhu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Jia Xu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Ming Wang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Wen-Yi Zhao
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Qiang Liu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Gang Zhao
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China.
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Bourguignon LYW. Matrix Hyaluronan-CD44 Interaction Activates MicroRNA and LncRNA Signaling Associated With Chemoresistance, Invasion, and Tumor Progression. Front Oncol 2019; 9:492. [PMID: 31293964 PMCID: PMC6598393 DOI: 10.3389/fonc.2019.00492] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 05/24/2019] [Indexed: 12/11/2022] Open
Abstract
Tumor malignancies involve cancer cell growth, issue invasion, metastasis and often drug resistance. A great deal of effort has been placed on searching for unique molecule(s) overexpressed in cancer cells that correlate(s) with tumor cell-specific behaviors. Hyaluronan (HA), one of the major ECM (extracellular matrix) components have been identified as a physiological ligand for surface CD44 isoforms which are frequently overexpressed in malignant tumor cells during cancer progression. The binding interaction between HA and CD44 isoforms often stimulates aberrant cellular signaling processes and appears to be responsible for the induction of multiple oncogenic events required for cancer-specific phenotypes and behaviors. In recent years, both microRNAs (miRNAs) (with ~20–25 nucleotides) and long non-coding RNAs (lncRNAs) (with ~200 nucleotides) have been found to be abnormally expressed in cancer cells and actively participate in numerous oncogenic signaling events needed for tumor cell-specific functions. In this review, I plan to place a special emphasis on HA/CD44-induced signaling pathways and the presence of several novel miRNAs (e.g., miR-10b/miR-302/miR-21) and lncRNAs (e.g., UCA1) together with their target functions (e.g., tumor cell migration, invasion, and chemoresistance) during cancer development and progression. I believe that important information can be obtained from these studies on HA/CD44-activated miRNAs and lncRNA that may be very valuable for the future development of innovative therapeutic drugs for the treatment of matrix HA/CD44-mediated cancers.
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Affiliation(s)
- Lilly Y W Bourguignon
- Endocrine Unit (111N2), Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, United States
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LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: updates in recent years. Appl Microbiol Biotechnol 2019; 103:4649-4677. [PMID: 31062053 DOI: 10.1007/s00253-019-09837-5] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 04/07/2019] [Accepted: 04/08/2019] [Indexed: 12/15/2022]
Abstract
Long noncoding RNA (lncRNA) is a kind of RNAi molecule composed of hundreds to thousands of nucleotides. There are several major types of functional lncRNAs which participate in some important cellular pathways. LncRNA-RNA interaction controls mRNA translation and degradation or serves as a microRNA (miRNA) sponge for silencing. LncRNA-protein interaction regulates protein activity in transcriptional activation and silencing. LncRNA guide, decoy, and scaffold regulate transcription regulators of enhancer or repressor region of the coding genes for alteration of expression. LncRNA plays a role in cellular responses including the following activities: regulation of chromatin structural modification and gene expression for epigenetic and cell function control, promotion of hematopoiesis and maturation of immunity, cell programming in stem cell and somatic cell development, modulation of pathogen infection, switching glycolysis and lipid metabolism, and initiation of autoimmune diseases. LncRNA, together with miRNA, are considered the critical elements in cancer development. It has been demonstrated that tumorigenesis could be driven by homeostatic imbalance of lncRNA/miRNA/cancer regulatory factors resulting in biochemical and physiological alterations inside the cells. Cancer-driven lncRNAs with other cellular RNAs, epigenetic modulators, or protein effectors may change gene expression level and affect the viability, immortality, and motility of the cells that facilitate cancer cell cycle rearrangement, angiogenesis, proliferation, and metastasis. Molecular medicine will be the future trend for development. LncRNA/miRNA could be one of the potential candidates in this category. Continuous studies in lncRNA functional discrepancy between cancer cells and normal cells and regional and rational genetic differences of lncRNA profiles are critical for clinical research which is beneficial for clinical practice.
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Chen C, Tang X, Liu Y, Zhu J, Liu J. Induction/reversal of drug resistance in gastric cancer by non-coding RNAs (Review). Int J Oncol 2019; 54:1511-1524. [PMID: 30896792 PMCID: PMC6438417 DOI: 10.3892/ijo.2019.4751] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/21/2019] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer (GC) is one of the most prevalent and malignant types of cancer worldwide. In China, it is the second most common type of cancer and the malignancy with the highest incidence and mortality rate. Chemotherapy for GC is not always effective due to the development of drug resistance. Drug resistance, which is frequently observed in GC, undermines the success rate of chemotherapy and the survival of patients with GC. The dysregulation of non‑coding RNAs (ncRNAs), primarily microRNAs (miRNAs or miRs) and long non‑coding RNAs (lncRNAs), is involved in the development of GC drug resistance via numerous mechanisms. These mechanisms contribute to the involvement of a large and complex network of ncRNAs in drug resistance. In this review, we focus on and summarize the latest research on the specific mechanisms of action of miRNAs and lncRNAs that modulate drug resistance in GC. In addition, we discuss future prospects and clinical applications of ncRNAs as potential targeted therapies against the chemoresistance of GC.
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Affiliation(s)
- Chao Chen
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Xiaohuan Tang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Yuanda Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Jiaming Zhu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
| | - Jingjing Liu
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
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Ding H, Sun J, Li R, Wang G. Retracted Article: Long non-coding RNA GACAT1 alleviates doxorubicin and vincristine resistance through a PTEN/AKT/mTOR/S6K1 regulatory pathway in gastric cancer. RSC Adv 2019; 9:8048-8055. [PMID: 35521206 PMCID: PMC9061239 DOI: 10.1039/c8ra10030f] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 02/22/2019] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is a major global health problem. Chemotherapy is a common therapeutic strategy for cancers including GC. However, chemoresistance strikingly limits the clinical applications of chemotherapeutic drugs. Long non-coding RNAs (lncRNAs) have been widely reported to be implicated in the pathogenesis and chemoresistance of cancers including GC. Our work aims to investigate the roles and molecular mechanisms of lncRNA gastric cancer-associated transcript 1 (GACAT1) in regulating doxorubicin (ADR) and vincristine (VCR) resistance in GC. In this text, RT-qPCR assay showed that GACAT1 expression was markedly reduced in ADR- or VCR-resistant GC (SGC7901/ADR or SGC7901/VCR) cells and GC tissues. CCK-8 assay and flow cytometry analysis revealed that GACAT1 overexpression alleviated the resistance of GC cells to ADR and VCR. RT-qPCR and western blot assay disclosed that GACAT1 deactivated the AKT/mTOR/S6K1 signaling pathway and promoted PTEN expression in SGC7901/ADR or SGC7901/VCR cells. Restoration experiments demonstrated that GACAT1 attenuated ADR or VCR resistance by regulating the PTEN/AKT/mTOR/S6K1 pathway in SGC7901/ADR or SGC7901/VCR cells. In vivo experiments demonstrated that GACAT1 overexpression inhibited tumor growth and enhanced ADR- or VCR-mediated anti-tumor effects in GC xenograft tumor models. Taken together, these data revealed that GACAT1 weakened the resistance of GC cells to ADR and VCR by the PTEN/AKT/mTOR/S6K1 regulatory pathway in vitro and in vivo, shedding new light on GACAT1 upregulation as a potential strategy to alleviate chemoresistance in GC.
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Affiliation(s)
- Hengxuan Ding
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University Jianshe Road 1 Zhengzhou 450052 P. R. China +86-0371-67967137
| | - Junfeng Sun
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University Jianshe Road 1 Zhengzhou 450052 P. R. China +86-0371-67967137
| | - Ruixin Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University Jianshe Road 1 Zhengzhou 450052 P. R. China +86-0371-67967137
| | - Guojun Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University Jianshe Road 1 Zhengzhou 450052 P. R. China +86-0371-67967137
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Cheshomi H, Matin MM. Exosomes and their importance in metastasis, diagnosis, and therapy of colorectal cancer. J Cell Biochem 2019; 120:2671-2686. [PMID: 30246315 DOI: 10.1002/jcb.27582] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 08/07/2018] [Indexed: 01/24/2023]
Abstract
Extracellular vesicles are known as actual intermediaries of intercellular communications, such as biological signals and cargo transfer between different cells. A variety of cells release the exosomes as nanovesicular bodies. Exosomes contain different compounds such as several types of nucleic acids and proteins. In this study, we focused on exosomes in colorectal cancer as good tools that can be involved in various cancer-related processes. Furthermore, we summarize the advantages and disadvantages of exosome extraction methods and review related studies on the role of exosomes in colorectal cancer. Finally, we focus on reports available on relations between mesenchymal stem cell-derived exosomes and colorectal cancer. Several cancer-related processes such as cancer progression, metastasis, and drug resistance of colorectal cancer are related to the cargoes of exosomes. A variety of molecules, especially proteins, microRNAs, and long noncoding RNAs, play important roles in these processes. The microenvironment features, such as hypoxia, also have very important effects on the properties of the origin cell-derived exosomes. On the other hand, exosomes derived from colorectal cancer cells also interfere with cancer chemoresistance. Furthermore, today it is known that exosomes and their contents can likely be very effective in noninvasive colorectal cancer diagnosis and therapy. Thus, exosomes, and especially their cargoes, play different key roles in various aspects of basic and clinical research related to both progression and therapy of colorectal cancer.
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Affiliation(s)
- Hamid Cheshomi
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Maryam M Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.,Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
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