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Luan X, Peng X, Hou Q, Liu J. LINC00892 as a Prognostic Biomarker in Lung Adenocarcinoma: Role in Immune Infiltration and EMT Suppression. J Immunol Res 2025; 2025:4341348. [PMID: 40308809 PMCID: PMC12041620 DOI: 10.1155/jimr/4341348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 03/10/2025] [Indexed: 05/02/2025] Open
Abstract
Lung adenocarcinoma (LUAD) is a prevalent and aggressive form of lung cancer with poor prognosis, largely due to late-stage diagnosis and limited therapeutic options. Recent studies suggest that long noncoding RNAs (lncRNAs) play critical roles in cancer progression and immune modulation, emerging as potential therapeutic targets. In this study, we investigated the expression and functional role of LINC00892 in LUAD using RNA sequencing data from The Cancer Genome Atlas (TCGA) and functional assays in vitro and in vivo. We found that LINC00892 is significantly downregulated in LUAD tissues compared to normal tissues, and lower LINC00892 expression correlates with poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI), particularly in younger patients and those with early-stage disease. Bioinformatic analyses revealed that LINC00892 expression is positively correlated with immune cell infiltration, including CD4+ and CD8+ T cells, and negatively correlated with tumor-promoting Th2 cells, suggesting its role in shaping the tumor immune microenvironment. In vitro functional assays showed that LINC00892 overexpression inhibits LUAD cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, LINC00892 upregulation was found to suppress epithelial-mesenchymal transition (EMT) by increasing E-cadherin expression and decreasing levels of N-cadherin, vimentin, and slug. Additionally, in an in vivo mouse xenograft model, LINC00892 overexpression suppressed tumor growth and metastasis, accompanied by enhanced immune cell infiltration such as CD4+ and CD8+ T cells. Collectively, these findings suggest that LINC00892 acts as a tumor suppressor in LUAD by modulating immune infiltration and EMT, highlighting its potential as a prognostic biomarker and therapeutic target.
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Affiliation(s)
- Xinyu Luan
- Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Xuxing Peng
- Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Qinghua Hou
- Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Jixian Liu
- Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
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Yang P, Gu H, Wu X, Chen G, Liu H, Chen Z. Tumour protein p53-activated lncRNA PGM5-AS1 suppresses lung cancer growth and stemness by targeting R-spondin1 via microRNA-1247-5p. Arch Physiol Biochem 2025:1-13. [PMID: 40035308 DOI: 10.1080/13813455.2025.2459318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 11/06/2024] [Accepted: 01/22/2025] [Indexed: 03/05/2025]
Abstract
OBJECTIVE This study was to investigated the inhibitory role of the tumour protein p53 (TP53)-activated PGM5-AS1 in lung cancer (LC) cell proliferation, invasion, and CSC-like properties and its underlying mechanisms. METHODS The effect of PGM5-AS1 on LC cell development was determined. Stem cell markers, aldehyde dehydrogenase activity in cells were tested, as well as the ability of stem cells to form spheroids. The interaction of PGM5-AS1 and TP53 was determined. The binding link of PGM5-AS1, miR-1247-5p, and R-spondin1 (RSPO1) was verified. RESULTS PGM5-AS1 was elevated by a combination of TP53 and PGM5-AS1 promoters. PGM5-AS1 was a molecular sponge of miR-1247-5p in LC cells, and miR-1247-5p targeted RSPO1. Elevating PGM5-AS1 or repressing miR-1247-5p restrained LC cell growth and stemness, which were reversed by depression of RSPO1. CONCLUSION This study conveys that TP53-elevated PGM5-AS1 mediates miR-1247-5p to target RSPO1, thereby inhibiting LC growth and stemness, representing a novel avenue for LC therapy.
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Affiliation(s)
- Peng Yang
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Hong Gu
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Xuanqin Wu
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Geng Chen
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Heng Liu
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
| | - Zhongliang Chen
- Department of Cardiothoracic and Vascular Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, Guangdong, China
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Guo J, Xie T, Zhang S. Linc00239 Promotes Colorectal Cancer Development via MicroRNA-182-5p/Metadherin Axis. Biochem Genet 2024; 62:1727-1741. [PMID: 37695492 DOI: 10.1007/s10528-023-10510-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 08/23/2023] [Indexed: 09/12/2023]
Abstract
Long non-coding RNAs (lncRNAs) are associated with colorectal cancer (CRC); however, CRC-related linc00239 functions have not been fully elucidated. Prognostic analysis of patients with CRC with linc00239 overexpression was performed using data from The Cancer Genome Atlas database. Cell Counting Kit-8 and Transwell were used to determine linc00239 functions for CRC cells. The lncRNA-miRNA-mRNA interaction network was used to screen target miRNAs and mRNAs regulated by linc00239. Quantitative real-time polymerase chain reaction and western blotting were used to confirm the miRNA and mRNA expression. Furthermore, a miRNA inhibitor was transfected into CRC cells, and cell function was evaluated. Results indicated a high linc00239 expression in the tumor tissue of patients with CRC. Transfection of linc00239 siRNA into SW480 and LOVO cells decreased cell proliferation, cell migration, and invasion. MiR-182-5p/metadherin (MTDH) axis is a downstream pathway of linc00239. MTDH expression, the activity of cell proliferation, migration, and invasion, which were suppressed by linc00239 siRNA, were partially attenuated when linc00239 siRNA and miR-182-5p inhibitor were co-transfected into the CRC cells. Furthermore, miR-182-5p expression was decreased and MTDH expression was promoted in CRC tissues. Altogether, linc00239 may promote CRC development through the miR-182-5p/MTDH axis.
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Affiliation(s)
- Jianian Guo
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
| | - Tingting Xie
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
| | - Shi Zhang
- Department of Surgical Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 Changgang East Road, Guangzhou, 510260, China.
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Fu B, Zhou F, Zhang J, Kong X, Ni B, Bu J, Xu S, He C. Sevoflurane attenuates proliferative and migratory activity of lung cancer cells via mediating the microRNA-100-3p/sterol O-Acyltransferase 1 axis. CHINESE J PHYSIOL 2023; 66:456-465. [PMID: 38149558 DOI: 10.4103/cjop.cjop-d-22-00124] [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] [Indexed: 12/28/2023] Open
Abstract
Recently, evidence has shown that microRNA-100-3p (miR-100-3p) has been revealed as a tumor suppressor in diverse human diseases, while its capability in lung cancer warrants further validation. In this work, we aimed to discuss the impact of sevoflurane on biological functions of lung cancer cells by modulating the miR-100-3p/sterol O-acyltransferase 1 (SOAT1) axis. Lung cancer cell lines (A549 and H460) were treated with various concentrations of sevoflurane. Cell viability, proliferation, migration, and invasion were evaluated using MTT, colony formation, wound healing, and transwell assays. Moreover, miR-100-3p and SOAT1 expressions were evaluated by reverse transcription-quantitative polymerase chain reaction in lung cancer cells. The target interaction between miR-100-3p and SOAT1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter gene assay. The findings of our work demonstrated that sevoflurane impeded the abilities on viability, proliferation, migration, and invasion of A549 and H460 cells. The expression of miR-100-3p was reduced, and SOAT1 expression was elevated in lung cancer cells. miR-100-3p targeted SOAT1. Besides, sevoflurane could lead to expressed improvement of miR-100-3p or limitation of SOAT1. Downregulation of miR-100-3p or upregulation of SOAT1 restored the suppression of sevoflurane on abilities of viability, proliferation, migration, and invasion in A549 and H460 cells. In the rescue experiment, downregulation of SOAT1 reversed the impacts of downregulation of miR-100-3p on sevoflurane on lung cancer cells. Collectively, our study provides evidence that sevoflurane restrained the proliferation and invasion in lung cancer cells by modulating the miR-100-3p/SOAT1 axis. This article provides a new idea for further study of the pathogenesis of lung cancer.
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Affiliation(s)
- Bicheng Fu
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Fucheng Zhou
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Jian Zhang
- Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Xianglong Kong
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Boxiong Ni
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Jianlong Bu
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Shidong Xu
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Changjun He
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
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Baba SK, Baba SK, Mir R, Elfaki I, Algehainy N, Ullah MF, Barnawi J, Altemani FH, Alanazi M, Mustafa SK, Masoodi T, Akil ASA, Bhat AA, Macha MA. Long non-coding RNAs modulate tumor microenvironment to promote metastasis: novel avenue for therapeutic intervention. Front Cell Dev Biol 2023; 11:1164301. [PMID: 37384249 PMCID: PMC10299194 DOI: 10.3389/fcell.2023.1164301] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 05/22/2023] [Indexed: 06/30/2023] Open
Abstract
Cancer is a devastating disease and the primary cause of morbidity and mortality worldwide, with cancer metastasis responsible for 90% of cancer-related deaths. Cancer metastasis is a multistep process characterized by spreading of cancer cells from the primary tumor and acquiring molecular and phenotypic changes that enable them to expand and colonize in distant organs. Despite recent advancements, the underlying molecular mechanism(s) of cancer metastasis is limited and requires further exploration. In addition to genetic alterations, epigenetic changes have been demonstrated to play an important role in the development of cancer metastasis. Long non-coding RNAs (lncRNAs) are considered one of the most critical epigenetic regulators. By regulating signaling pathways and acting as decoys, guides, and scaffolds, they modulate key molecules in every step of cancer metastasis such as dissemination of carcinoma cells, intravascular transit, and metastatic colonization. Gaining a good knowledge of the detailed molecular basis underlying lncRNAs regulating cancer metastasis may provide previously unknown therapeutic and diagnostic lncRNAs for patients with metastatic disease. In this review, we concentrate on the molecular mechanisms underlying lncRNAs in the regulation of cancer metastasis, the cross-talk with metabolic reprogramming, modulating cancer cell anoikis resistance, influencing metastatic microenvironment, and the interaction with pre-metastatic niche formation. In addition, we also discuss the clinical utility and therapeutic potential of lncRNAs for cancer treatment. Finally, we also represent areas for future research in this rapidly developing field.
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Affiliation(s)
- Sana Khurshid Baba
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Kashmir, India
| | - Sadaf Khursheed Baba
- Department of Microbiology, Sher-I-Kashmir Institute of Medical Science (SKIMS), Soura, Kashmir, India
| | - Rashid Mir
- Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Imadeldin Elfaki
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Naseh Algehainy
- Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohammad Fahad Ullah
- Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Jameel Barnawi
- Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Faisal H. Altemani
- Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohammad Alanazi
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Syed Khalid Mustafa
- Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Tariq Masoodi
- Human Immunology Department, Research Branch, Sidra Medicine, Doha, Qatar
| | - Ammira S. Alshabeeb Akil
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity, and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Ajaz A. Bhat
- Department of Human Genetics-Precision Medicine in Diabetes, Obesity, and Cancer Program, Sidra Medicine, Doha, Qatar
| | - Muzafar A. Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Kashmir, India
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Islam S, Mukherjee C. Molecular regulation of hypoxia through the lenses of noncoding RNAs and epitranscriptome. WILEY INTERDISCIPLINARY REVIEWS. RNA 2023; 14:e1750. [PMID: 35785444 DOI: 10.1002/wrna.1750] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 05/27/2022] [Accepted: 06/06/2022] [Indexed: 11/09/2022]
Abstract
Cells maintain homeostasis in response to environmental stress through specific cell stress responses. Hypoxic stress, well known to be associated with diverse solid tumors, is one of the main reasons for cancer-related mortality. Although cells can balance themselves well during hypoxic stress, the underlying molecular mechanisms are not well understood. The enhanced appreciation of diverse roles played by noncoding transcriptome and epigenome in recent years has brought to light the involvement of noncoding RNAs and epigenetic modifiers in hypoxic regulation. The emergence of techniques like deep sequencing has facilitated the identification of large numbers of long noncoding RNAs (lncRNAs) that are differentially regulated in various cancers. Similarly, proteomic studies have identified diverse epigenetic modifiers such as HATs, HDACs, DNMTs, polycomb groups of proteins, and their possible roles in the regulation of hypoxia. The crosstalk between lncRNAs and epigenetic modifiers play a pivotal role in hypoxia-induced cancer initiation and progression. Besides the lncRNAs, several other noncoding RNAs like circular RNAs, miRNAs, and so forth are also expressed during hypoxic conditions. Hypoxia has a profound effect on the expression of noncoding RNAs and epigenetic modifiers. Conversely, noncoding RNAs/epigenetic modifies can regulate the hypoxia signaling axis by modulating the stability of the hypoxia-inducible factors (HIFs). The focus of this review is to illustrate the molecular orchestration underlying hypoxia biology, especially in cancers, which can help in identifying promising therapeutic targets in hypoxia-induced cancers. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry.
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Affiliation(s)
- Safirul Islam
- Institute of Health Sciences (erstwhile School of Biotechnology), Presidency University, Kolkata, India
| | - Chandrama Mukherjee
- Institute of Health Sciences (erstwhile School of Biotechnology), Presidency University, Kolkata, India
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Xue F, Yang C, Yun K, Jiang C, Cai R, Liang M, Wang Q, Bian W, Zhou H, Liu Z, Zhu L. RETRACTED ARTICLE: Reduced LINC00467 elevates microRNA-125a-3p to suppress cisplatin resistance in non-small cell lung cancer through inhibiting sirtuin 6 and inactivating the ERK1/2 signaling pathway. Cell Biol Toxicol 2023; 39:365. [PMID: 34458953 DOI: 10.1007/s10565-021-09637-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 07/13/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Feng Xue
- Department of Oncology, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, China
| | - Chuan Yang
- Center of Endoscopy, Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin, 150036, Heilongjiang, China
| | - Keli Yun
- Department of Pharmacology, Pharmacy School of Guilin Medical University, Guilin, 541004, Guangxi, China
| | - Cailing Jiang
- Department of Oncology, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, China
| | - Rui Cai
- Department of Radiotherapy, Affiliated Hospital of Guilin Medical University, No.15 Lequn Road, Guilin, 541001, Guangxi, China
| | - Ming Liang
- Emergency Center of Nangang Branch, Heilongjiang Provincial Hospital, Harbin Institute of Technonlogy, Harbin, 150036, Heilongjiang, China
| | - Quan Wang
- Department of Medical Imaging, Heilongjiang Provincial Hospital, Harbin Institute of Technonlogy, Harbin, 150036, Heilongjiang, China
| | - Weixin Bian
- Department of Oncology, Heilongjiang Provincial Hospital, Harbin Institute of Technonlogy, Harbin, 150036, Heilongjiang, China
| | - Hang Zhou
- Department of Medical Imaging, Heilongjiang Provincial Hospital, Harbin Institute of Technonlogy, Harbin, 150036, Heilongjiang, China
| | - Zhipeng Liu
- Department of Medical Imaging, Heilongjiang Provincial Hospital, Harbin Institute of Technonlogy, Harbin, 150036, Heilongjiang, China
| | - Lin Zhu
- Department of Radiotherapy, Affiliated Hospital of Guilin Medical University, No.15 Lequn Road, Guilin, 541001, Guangxi, China.
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lnc-MRGPRF-6:1 Promotes M1 Polarization of Macrophage and Inflammatory Response through the TLR4-MyD88-MAPK Pathway. Mediators Inflamm 2022; 2022:6979117. [PMID: 35125964 PMCID: PMC8816599 DOI: 10.1155/2022/6979117] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 12/02/2021] [Accepted: 12/21/2021] [Indexed: 11/17/2022] Open
Abstract
Background. Macrophage-mediated inflammation plays an essential role in the development of atherosclerosis (AS). Long noncoding RNAs (lncRNAs), as crucial regulators, participate in this process. We identified that lnc-MRGPRF-6:1 was significantly upregulated in the plasma exosomes of coronary atherosclerotic disease (CAD) patients in a preliminary work. In the present study, we aim to assess the role of lnc-MRGPRF-6:1 in macrophage-mediated inflammatory process of AS. Methods. The correlation between lnc-MRGPRF-6:1 and inflammatory factors was estimated firstly in plasma exosomes of CAD patients. Subsequently, we established lnc-MRGPRF-6:1 knockout macrophage model via the CRISPR/Cas9 system. We then investigated the regulatory effects of lnc-MRGPRF-6:1 on macrophage polarization and foam cell formation. Eventually, transcriptome analysis by RNA sequencing was carried out to explore the contribution of differential genes and signaling pathways in this process. Results. lnc-MRGPRF-6:1 was highly expressed in the plasma exosomes of CAD patients and was positively correlated with the expression of inflammatory cytokines in plasma. lnc-MRGPRF-6:1 inhibition significantly reduced the formation of foam cells. The expression of lnc-MRGPRF-6:1 was upregulated in M1 macrophage, and lnc-MRGPRF-6:1 knockout decreased the polarization of M1 macrophage. lnc-MRGPRF-6:1 regulates macrophage polarization via the TLR4-MyD88-MAPK signaling pathway. Conclusions. lnc-MRGPRF-6:1 knockdown can inhibit M1 polarization of macrophage and inflammatory response through the TLR4-MyD88-MAPK signaling pathway. lnc-MRGPRF-6:1 is a vital regulator in macrophage-mediated inflammatory process of AS.
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Zhang Y, Zheng M, Zhang L, Yuan P, Zhou J, Wang Y, Wang H. LncRNA LOXL1-AS1 Facilitates the Oncogenic Character in Cervical Cancer by the miR-526b-5p /LYPLA1 Axis. Biochem Genet 2022; 60:1298-1312. [PMID: 34984578 DOI: 10.1007/s10528-021-10182-4] [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: 08/26/2021] [Accepted: 12/20/2021] [Indexed: 11/02/2022]
Abstract
Increasing reports demonstrate that long noncoding RNAs participate in the regulation of numerous malignancies, cervical cancer included. Although lncRNA LOXL1 antisense RNA 1 has been commonly accepted to be an oncogene in many cancers. Here, the role of LOXL1-AS1 in CC still need to be explored. In this study, LOXL1-AS1 was found elevated in CC tissues and cells. LOXL1-AS1 depletion restrained CC cell proliferation, migration, invasion, and angiogenesis in vivo. Furthermore, we found that LOXL1-AS1 upregulated Lysophospholipase 1 expression via sequestering miR-526b-5p. Rescue assays revealed that overexpression of LYPLA1 reversed the LOXL1-AS1 silencing-induced inhibitory effects on the malignant phenotypes of CC cells. To conclude, this study showed that LOXL1-AS1 facilitates cellular process in CC via functioning as a miR-526b-5p sponge.
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Affiliation(s)
- Yanhua Zhang
- Department of Obstetrics and Gynecology, Binhai County People's Hospital, No. 248, Fudong Middle Road, Yancheng, 224599, Jiangsu, China
| | - Meng Zheng
- Department of Obstetrics and Gynecology, Binhai County People's Hospital, No. 248, Fudong Middle Road, Yancheng, 224599, Jiangsu, China
| | - Lingyan Zhang
- Department of Obstetrics and Gynecology, Binhai County People's Hospital, No. 248, Fudong Middle Road, Yancheng, 224599, Jiangsu, China
| | - Ping Yuan
- Department of Obstetrics and Gynecology, Binhai County People's Hospital, No. 248, Fudong Middle Road, Yancheng, 224599, Jiangsu, China
| | - Jianbo Zhou
- Department of Obstetrics and Gynecology, Binhai County People's Hospital, No. 248, Fudong Middle Road, Yancheng, 224599, Jiangsu, China
| | - Yongfang Wang
- Department of Obstetrics and Gynecology, Binhai County People's Hospital, No. 248, Fudong Middle Road, Yancheng, 224599, Jiangsu, China
| | - Haihong Wang
- Department of Obstetrics and Gynecology, Binhai County People's Hospital, No. 248, Fudong Middle Road, Yancheng, 224599, Jiangsu, China.
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Yang Q, Dong YJ. LncRNA SNHG20 promotes migration and invasion of ovarian cancer via modulating the microRNA-148a/ROCK1 axis. J Ovarian Res 2021; 14:168. [PMID: 34836544 PMCID: PMC8626962 DOI: 10.1186/s13048-021-00889-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 09/29/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Ovarian cancer (OC) is characterized by early metastasis and poor prognosis, which threatens the health of women worldwide. Small nucleolar RNA host gene 20 (SNHG20), a long noncoding RNA (lncRNA), has been verified to be significantly up-regulated in several tumors, including OC. MicroRNA-148a (miR-148a)/rho-kinase1 (ROCK1) axis plays an important role in the modulation of tumor development. However, whether SNHG20 can regulate OC progression through miR-148a/ROCK1 axis remains unclear. Normal human ovarian epithelial cell line and four OC cell lines were adopted for in vitro experiments. Real-time PCR was performed to assess the levels of SNHG20 and miR-148a. OC cell proliferation, apoptosis, invasion and migration were detected using clone formation, flow cytometry, transwell, and wound healing assays, respectively. Tumor xenograft assay was applied to evaluate the effect of SNHG20 on tumor growth in vivo. RESULTS Significant higher expression of SNHG20 was observed in OC cell lines. SNHG20 markedly promoted the invasion, migration, proliferation and inhibited the apoptosis of OC cells. SNHG20 enhanced ROCK1 expression by sponging miR-148a, and the direct binding between SNHG20/ROCK1 and miR-148a was identified. CONCLUSION SNHG20 promoted invasion and migration of OC via targeting miR-148a/ROCK1 axis. The present research may provide a novel insight for the therapeutic strategies of OC.
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Affiliation(s)
- Qi Yang
- Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130000, Jilin Province, P. R. China.
| | - Yu-Jie Dong
- Department of Emergency, China-Japan Union Hospital of Jilin University, Changchun, 130000, P. R. China
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Ding H, Zhang L, Zhang C, Song J, Jiang Y. Screening of Significant Biomarkers Related to Prognosis of Cervical Cancer and Functional Study Based on lncRNA-associated ceRNA Regulatory Network. Comb Chem High Throughput Screen 2021; 24:472-482. [PMID: 32729415 DOI: 10.2174/1386207323999200729113028] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 05/28/2020] [Accepted: 06/15/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cervical cancer (CESC), which threatens the health of women, has a very high recurrence rate. PURPOSES This study aimed to identify the signature long non-coding RNAs (lncRNAs) associated with the prognosis of CESC and predict the prognostic survival rate with the clinical risk factors. METHODS The CESC gene expression profiling data were downloaded from TCGA database and NCBI Gene Expression Omnibus. Afterwards, the differentially expressed RNAs (DERs) were screened using limma package of R software. R package "survival" was then used to screen the signature lncRNAs associated with independently recurrence prognosis, and a nomogram recurrence rate model based on these signature lncRNAs was constructed to predict the 3-year and 5-year survival probability of CESC. Finally, a competing endogenous RNAs (ceRNA) regulatory network was proposed to study the functions of these genes. RESULTS We obtained 305 DERs significantly associated with prognosis. Afterwards, a risk score (RS) prediction model was established using the screened 5 signature lncRNAs associated with independently recurrence prognosis (DLEU1, LINC01119, RBPMS-AS1, RAD21-AS1 and LINC00323). Subsequently, a nomogram recurrence rate model, proposed with Pathologic N and RS model status, was found to have a good prediction ability for CESC. In ceRNA regulatory network, LINC00323 and DLEU1 were hub nodes which targeted more miRNAs and mRNAs. After that, 15 GO terms and 3 KEGG pathways were associated with recurrence prognosis and showed that the targeted genes PTK2, NRP1, PRKAA1 and HMGCS1 might influence the prognosis of CESC. CONCLUSION The signature lncRNAs can help improve our understanding of the development and recurrence of CESC and the nomogram recurrence rate model can be applied to predict the survival rate of CESC patients in clinical practice.
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Affiliation(s)
- Haiyan Ding
- Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Changchun, Jilin Province 130041, China
| | - Li Zhang
- Department of Emergency Medicine, Second Hospital of Jilin University, Changchun, Jilin Province 130041, China
| | - Chunmiao Zhang
- Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Changchun, Jilin Province 130041, China
| | - Jie Song
- Department of Hepatobiliary and Pancreatic Medicine, Second Hospital of Jilin University, Changchun, Jilin Province 130041, China
| | - Ying Jiang
- Department of Obstetrics and Gynecology, Second Hospital of Jilin University, Changchun, Jilin Province 130041, China
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Xu J, Wang J, Liu L, Chen L, Hu S, Liu F. MicroRNA -196b is related to the overall survival of patients with esophageal squamous cell carcinoma and facilitates tumor progression by regulating SOCS2 (Suppressor Of Cytokine Signaling 2). Bioengineered 2021; 12:7737-7746. [PMID: 34605350 PMCID: PMC8806835 DOI: 10.1080/21655979.2021.1982329] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is common cancer in China. At the same time, microRNA-196b (miR-196b) has different promotion/inhibition effects in different cancers. The study aims to reveal the role of miR-196b in ESCC and explore its prognostic value. The expression of miR-196b in ESCC samples and cell lines was detected to explore the expression pattern of miR-196b in ESCC. Kaplan-Meier method was conducted for survival rate and Multivariate Cox analysis was used to explore the clinical significance of miR-196b in ESCC. The Cell Counting Kit-8 (CCK-8) assay, transwell migration and invasion tests were used to determine the biological function of miR-196b in ESCC. The relationship of miR-196b and SOCS2 in ESCC was detected by luciferase activity assay and RIP assay. Both in ESCC tissues and cell lines, miR-196b expression was up-regulated. miR-196b expression is related to TNM stage and lymph node metastasis. Combining with the results of Multivariate Cox regression analysis, miR-196b may be a potential independent prognostic marker for ESCC patients. The results of the functional analysis showed that miR-196b inhibitor can reduce cell proliferation, migration and invasion in ESCC cells. Besides, the suppressor of cytokine signaling 2 (SOCS2) is the target of miR-196b in ESCC. miR-196b may exist as a tumor-promoting factor in ESCC and enhance the proliferation abilities, migration capacities, and invasion potential of ESCC cells by targeting SOCS2. miR-196b and SOCS2 have a close negative correlation in ESCC, which may be used as a clinically poor prognostic biomarker and therapeutic target for ESCC.
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Affiliation(s)
- Jinlong Xu
- Department of Cardiothoracic Surgery, Zhucheng People's Hospital, Weifang, Shandong, China
| | - Jinmei Wang
- Department of Outpatient Operating Room, Zhucheng People's Hospital, Weifang, Shandong, China
| | - Lili Liu
- Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Lin Chen
- Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Songliu Hu
- Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Feng Liu
- Department of Cardiothoracic Surgery, Zhucheng People's Hospital, Weifang, Shandong, China
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Feng SG, Bhandari R, Ya L, Zhixuan B, Qiuhui P, Jiabei Z, Sewi M, Ni Z, Jing W, Fenyong S, Ji M, Bhandari R. SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis. J Cancer 2021; 12:6031-6049. [PMID: 34539877 PMCID: PMC8425203 DOI: 10.7150/jca.60748] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 07/29/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Hepatoblastoma is a common hepatic tumor occurring in children between 0-5 years. Accumulating studies have shown lncRNA's potential role in distinct cancer progression and development, including hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated with the progression of distinct human cancers, but, its specific molecular mechanisms in hepatoblastoma is not unknown. Methods: In this study, we estimated SNHG9 expression in hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated SNHG9 expression in hepatoblastoma cell lines and then determined cell proliferation (CCK-8), colony formation, and cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pull down and Spemann's Pearson correlation coefficient assay were performed to establish the interaction between SNHG9, WNt3a and miR- 23a-5p. A xenograft in-vivo tumorgenicity test was performed to elucidate the role of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drug resistance in hepatoblastoma was also determined. Results: SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogenic activity while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. The xenograft tumorgenicity test showed SNHG9 downregulation significantly inhibited the tumor growth in BALB/c mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma. Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.
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Affiliation(s)
- Sun Gui Feng
- Department of Clinical Laboratory Medicine, Chengdu Second Peoples Hospital, Chengdu, Sichuan 610021, PR China.,Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
| | - Rajeev Bhandari
- Department of Clinical Laboratory Medicine, Chengdu Second Peoples Hospital, Chengdu, Sichuan 610021, PR China
| | - Liu Ya
- Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
| | - Bian Zhixuan
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Pan Qiuhui
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Zhu Jiabei
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Mao Sewi
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Zhen Ni
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Wang Jing
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Sun Fenyong
- Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
| | - Ma Ji
- Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Ramesh Bhandari
- Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China
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LINC01342 silencing upregulates microRNA-508-5p to inhibit progression of lung cancer by reducing cysteine-rich secretory protein 3. Cell Death Discov 2021; 7:238. [PMID: 34504061 PMCID: PMC8429695 DOI: 10.1038/s41420-021-00613-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/27/2021] [Accepted: 07/19/2021] [Indexed: 12/27/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) are critical players during cancer progression. Nevertheless, the effect of most lncRNAs in lung cancer (LC) remains unclear. We aimed to explore the role of LINC01342 in LC development through the microRNA-508-5p (miR-508-5p)/cysteine-rich secretory protein 3 (CRISP3) axis. LINC01342, miR-508-5p, and CRISP3 expression in clinical samples and cell lines were determined, and their correlations in LC were analyzed. The prognostic role of LINC01342 in LC patients was evaluated. LC cells were screened and, respectively, transfected to alter the expression of LINC01342, miR-508-5p, and CRISP3. Then, proliferation, migration, invasion, and apoptosis of transfected LC cells were determined, and the in vivo tumor growth was observed as well. Binding relationships between LINC01342 and miR-508-5p, and between miR-508-5p and CRISP3 were identified. LINC01342 and CRISP3 were upregulated and miR-508-5p was downregulated in LC tissues and cells. High LINC01342 expression indicated a poor prognosis of LC patients. The LINC01342/CRISP3 silencing or miR-508-5p elevation inhibited proliferation, migration, and invasion of LC cells and promoted LC cell apoptosis, and also suppressed the in vivo tumor growth. LINC01342 bound to miR-508-5p and miR-508-5p targeted CRISP3. LINC01342 plays a prognostic role in LC and LINC01342 silencing upregulates miR-508-5p to inhibit the progression of LC by reducing CRISP3.
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15
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Circulating lncRNA UCA1 and lncRNA PGM5-AS1 act as potential diagnostic biomarkers for early-stage colorectal cancer. Biosci Rep 2021; 41:229154. [PMID: 34212174 PMCID: PMC8276091 DOI: 10.1042/bsr20211115] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/29/2021] [Accepted: 06/29/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common and significant malignant diseases worldwide. In the present study, we evaluated two long non-coding RNAs (lncRNAs) in CRC patients as diagnostic markers for early-stage CRC. METHODS Using Gene Expression Omnibus (GEO) datasets GSE102340, GSE126092, GSE109454 and GSE115856, 14 differentially expressed lncRNAs were identified between cancer and adjacent tissues, among which, the two most differentially expressed were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR) in 200 healthy controls and 188 CRC patients. A receiver operating characteristic (ROC) analysis was employed to evaluate the diagnostic accuracy for CRC. RESULTS From four GEO datasets, three up-regulated and eleven down-regulated lncRNAs were identified in CRC tissues, among which, lncRNA urothelial carcinoma-associated 1 (UCA1) and lncRNA phosphoglucomutase 5-antisense RNA 1 (PGM5-AS1) were the most significantly up- and down-regulated lncRNAs in CRC patient plasma, respectively. The area under the ROC curve was calculated to be 0.766, 0.754 and 0.798 for UCA1, PGM5-AS1 and the combination of these two lncRNAs, respectively. Moreover, the diagnostic potential of these two lncRNAs was even higher for the early stages of CRC. The combination of UCA1 and PGM5-AS1 enhanced the AUC to 0.832, and when the lncRNAs were used with carcinoembryonic antigen (CEA), the AUC was further improved to 0.874. CONCLUSION In the present study, we identified two lncRNAs, UCA1 and PGM5-AS1, in CRC patients' plasma, which have the potential to be used as diagnostic biomarkers of CRC.
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Yao J, Yang Z, Yang J, Wang ZG, Zhang ZY. Long non-coding RNA FEZF1-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma via targeting miR-107/Wnt/β-catenin axis. Aging (Albany NY) 2021; 13:13726-13738. [PMID: 34023817 PMCID: PMC8202841 DOI: 10.18632/aging.202960] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Accepted: 04/06/2021] [Indexed: 12/18/2022]
Abstract
Hepatocellular carcinoma (HCC) is a public health problem around the world, with the molecular mechanisms being still incompletely clear. This study was carried out to explore the role and mechanism of long-noncoding RNA (lncRNA) FEZF1-AS1 in HCC progression. RNA sequencing and quantitative real time polymerase chain reaction (qRT- PCR) were applied to identify differently expressed lncRNAs in HCC tissues and adjacent normal tissues. CCK8 assay was adopted to test cell proliferation and flow cytometry was taken to detect cell apoptosis. Wound healing assay and transwell experiment were performed to determine cell migration and invasion. To validate the function of lncRNA FEZF1-AS1 in vivo, tumor-burdened models were established. The results showed that lncRNA FEZF1-AS1 level was prominently enhanced in HCC tumor specimens and overexpression of FEZF1-AS1 promoted the proliferation, migration and invasion of HCC cells. In mechanism, overexpression of FEZF1-AS1 reduced the expression of miR-107 which inhibited the activation of Wnt/β-catenin signaling. Overexpression of β-catenin promoted cell proliferation, migration and invasion which were inhibited by FEZF1-AS1 downregulation. In conclusion, our study demonstrated that FEZF1-AS1 promoted HCC progression through activating Wnt/β-catenin signaling by targeting miR-107, which provided a novel target for the therapy of HCC.
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Affiliation(s)
- Jing Yao
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
| | - Zhe Yang
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
| | - Jun Yang
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
| | - Zhi-Gang Wang
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
| | - Zheng-Yun Zhang
- Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
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Wang M, Liu H, Wu W, Zhao J, Song G, Chen X, Wang R, Shao C, Li J, Wang H, Wang Q, Feng X. Identification of Differentially Expressed Plasma lncRNAs As Potential Biomarkers for Breast Cancer. Clin Breast Cancer 2021; 22:e135-e141. [PMID: 34119428 DOI: 10.1016/j.clbc.2021.05.003] [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: 02/02/2021] [Revised: 04/26/2021] [Accepted: 05/08/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Breast cancer is the most common malignant tumor in women and is not easy to diagnose. Increasing evidence has underscored that long non-coding RNAs (lncRNAs) play important regulatory roles in the occurrence and progression of many cancers, including breast cancer. We aimed to identify lncRNAs in plasma as potential biomarkers for breast cancer. PATIENTS AND METHODS We analyzed the Gene Expression Omnibus (GEO) datasets GSE22820, GSE42568, and GSE65194 to identify the common differential genes between cancer tissues and adjacent tissues. Then 14 lncRNAs were identified among the common differential genes and validated by using real-time quantitative polymerase chain reaction in 92 patients with breast cancer and 100 healthy controls. Receiver operating characteristic (ROC) curves were constructed to evaluate their diagnostic value for breast cancer. RESULTS Integrated analysis of the GEO datasets identified three significantly upregulated and 11 downregulated lncRNAs in breast cancer tissues. Compared with healthy controls, MIAT was significantly upregulated in breast cancer patient plasma, and LINC00968 and LINC01140 were significantly downregulated. ROC curve analysis suggested that these three lncRNAs can discriminate breast cancer from healthy individual with high specificity and sensitivity. CONCLUSION This research identified three differentially expressed lncRNAs in breast cancer patient plasma. Our data suggest that these three lncRNAs can be used as potential diagnostic biomarkers of breast cancer.
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Affiliation(s)
- Minghui Wang
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Huilin Liu
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Wenyao Wu
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Jinxia Zhao
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Guanghui Song
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Xi Chen
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Rong Wang
- Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Changfeng Shao
- Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Jing Li
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Haiyan Wang
- Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Qing Wang
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | - Xiaodong Feng
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
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Ming H, Li B, Zhou L, Goel A, Huang C. Long non-coding RNAs and cancer metastasis: Molecular basis and therapeutic implications. Biochim Biophys Acta Rev Cancer 2021; 1875:188519. [PMID: 33548345 DOI: 10.1016/j.bbcan.2021.188519] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/29/2021] [Accepted: 01/29/2021] [Indexed: 02/08/2023]
Abstract
Cancer metastasis, defined by the epithelial to mesenchymal transition (EMT) of tumor cells, disseminates from the primary site to progressively colonize in distant tissues, and accounts for most cancer-associated deaths. However, studies on the molecular basis of cancer metastasis are still in their infancy. Besides genetic mutations, accumulating evidence indicates that epigenetic alterations also contribute in a major way to the refractory nature of cancer metastasis. Considered as one of the essential epigenetic regulators, long non-coding RNAs (lncRNAs) can act as signaling regulators, decoys, guides and scaffolds, modulating key molecules in every step of cancer metastasis including dissemination of carcinoma cells, intravascular transit, and metastatic colonization. Although still having limited clinical application, it is encouraging to witness that several lncRNAs, including CCAT1 and HOTAIR, are under clinical evaluation as potential biomarkers for cancer staging and assessment of metastatic potential. In this review, we focus on the molecular mechanisms underlying lncRNAs in the regulation of cancer metastasis and discuss their clinical potential as novel therapeutic targets as well as their diagnostic and prognostic significance for cancer treatment. Gaining clear insights into the detailed molecular basis underlying lncRNA-modulated cancer metastasis may provide previously unrecognized diagnostic and therapeutic strategies for metastatic patients.
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Affiliation(s)
- Hui Ming
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Bowen Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Li Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, 1218 S. Fifth Avenue, Suite 2226, Biomedical Research Center, Monrovia, CA 91016, USA.
| | - Canhua Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China; School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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LINC00205 promotes malignancy in lung cancer by recruiting FUS and stabilizing CSDE1. Biosci Rep 2021; 40:226130. [PMID: 32808651 PMCID: PMC7536328 DOI: 10.1042/bsr20190701] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 12/20/2022] Open
Abstract
Lung cancer (LC) is characterized by high morbidity and mortality. Numerous long noncoding RNAs (lncRNAs) have been reported to be involved in the initiation and progression of human cancers, including LC. Long intergenic non-protein coding RNA 205 (LINC00205) is identified as a novel lncRNA, which has only been unmasked to be a potential cancer promoter in hepatocellular carcinoma and pancreatic cancer. The biologic function and the molecular mechanism of LINC00205 in LC require to be investigated. In the present study, we observed the elevated expression of LINC00205 in LC tissues and cells through real-time quantitative PCR (RT-qPCR). Additionally, silencing LINC00205 inhibited LC cell growth and migration, but aggravated cell apoptosis. Moreover, we found that LINC00205 recruited FUS to maintain the mRNA stability of cold shock domain containing E1 (CSDE1) and therefore up-regulated CSDE1 expression in LC. Further, the effects of LINC00205 on LC cell proliferation, apoptosis and migration were all erased by CSDE1 overexpression. These findings demonstrated that LINC00205 facilitates malignant phenotypes in LC by recruiting FUS to stabilize CSDE1, suggesting LINC00205 as a potential target for LC therapy.
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Li Z, Cai S, Li H, Gu J, Tian Y, Cao J, Yu D, Tang Z. Developing a lncRNA Signature to Predict the Radiotherapy Response of Lower-Grade Gliomas Using Co-expression and ceRNA Network Analysis. Front Oncol 2021; 11:622880. [PMID: 33767991 PMCID: PMC7985253 DOI: 10.3389/fonc.2021.622880] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/15/2021] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Lower-grade glioma (LGG) is a type of central nervous system tumor that includes WHO grade II and grade III gliomas. Despite developments in medical science and technology and the availability of several treatment options, the management of LGG warrants further research. Surgical treatment for LGG treatment poses a challenge owing to its often inaccessible locations in the brain. Although radiation therapy (RT) is the most important approach in this condition and offers more advantages compared to surgery and chemotherapy, it is associated with certain limitations. Responses can vary from individual to individual based on genetic differences. The relationship between non-coding RNA and the response to radiation therapy, especially at the molecular level, is still undefined. METHODS In this study, using The Cancer Genome Atlas dataset and bioinformatics, the gene co-expression network that is involved in the response to radiation therapy in lower-grade gliomas was determined, and the ceRNA network of radiotherapy response was constructed based on three databases of RNA interaction. Next, survival analysis was performed for hub genes in the co-expression network, and the high-efficiency biomarkers that could predict the prognosis of patients with LGG undergoing radiotherapy was identified. RESULTS We found that some modules in the co-expression network were related to the radiotherapy responses in patients with LGG. Based on the genes in those modules and the three databases, we constructed a ceRNA network for the regulation of radiotherapy responses in LGG. We identified the hub genes and found that the long non-coding RNA, DRAIC, is a potential molecular biomarker to predict the prognosis of radiotherapy in LGG.
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Affiliation(s)
- Zhongyang Li
- School of Radiation Medicine and Protection, Soochow University Medical College (SUMC), Suzhou, China
| | - Shang Cai
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China
| | - Huijun Li
- Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Provincial Key Laboratory of Geriatrics Prevention and Translational Medicine, School of Public Health, Soochow University Medical College, Suzhou, China
| | - Jincheng Gu
- Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Provincial Key Laboratory of Geriatrics Prevention and Translational Medicine, School of Public Health, Soochow University Medical College, Suzhou, China
| | - Ye Tian
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China
| | - Jianping Cao
- School of Radiation Medicine and Protection, Soochow University Medical College (SUMC), Suzhou, China
- School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China
| | - Dong Yu
- School of Radiation Medicine and Protection, Soochow University Medical College (SUMC), Suzhou, China
| | - Zaixiang Tang
- Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, China
- Jiangsu Provincial Key Laboratory of Geriatrics Prevention and Translational Medicine, School of Public Health, Soochow University Medical College, Suzhou, China
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Inhibition of long non-coding RNA XIST upregulates microRNA-149-3p to repress ovarian cancer cell progression. Cell Death Dis 2021; 12:145. [PMID: 33542185 PMCID: PMC7862378 DOI: 10.1038/s41419-020-03358-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 11/30/2020] [Accepted: 12/02/2020] [Indexed: 01/02/2023]
Abstract
Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play critical roles in human diseases. We aimed to clarify the role of lncRNA X-inactive specific transcript (XIST)/miR-149-3p/forkhead box P3 (FOXP3) axis in ovarian cancer (OC) cell growth. XIST, miR-149-3p and FOXP3 expression in OC tissues and cell lines was assessed, and the predictive role of XIST in prognosis of OC patients was analyzed. The OC cell lines were screened and accordingly treated with silenced/overexpressed XIST plasmid or miR-149-3p mimic/inhibitor, and then the proliferation, invasion, migration, colony formation ability, apoptosis, and cell cycle distribution of OC cells were measured. Effect of altered XIST and miR-149-3p on tumor growth in vivo was observed. Online website prediction and dual luciferase reporter gene were implemented to detect the targeting relationship of lncRNA XIST, miR-149-3p, and FOXP3. XIST and FOXP3 were upregulated, whereas miR-149-3p was downregulated in OC tissues and cells. High XIST expression indicated a poor prognosis of OC. Inhibition of XIST or elevation of miR-149-3p repressed proliferation, invasion, migration, and colony formation ability, and promoted apoptosis and cell cycle arrest of HO-8910 cells. In SKOV3 cells upon treatment of overexpressed XIST or reduction of miR-149-3p, there exhibited an opposite tendency. Based on online website prediction, dual luciferase reporter gene, and RNA pull-down assays, we found that there was a negative relationship between XIST and miR-149-3p, and miR-149-3p downregulated FOXP3 expression. This study highlights that knockdown of XIST elevates miR-149-3p expression to suppress malignant behaviors of OC cells, thereby inhibiting OC development.
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Long non-coding RNA linc00665 inhibits CDKN1C expression by binding to EZH2 and affects cisplatin sensitivity of NSCLC cells. MOLECULAR THERAPY-NUCLEIC ACIDS 2021; 23:1053-1065. [PMID: 33664990 PMCID: PMC7887328 DOI: 10.1016/j.omtn.2021.01.013] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 01/14/2021] [Indexed: 12/13/2022]
Abstract
Long non-coding RNAs (lncRNAs) can play significant regulatory roles in cells that affect the development and acquired drug resistance of lung cancer. Herein, we report that lncRNA linc00665 is significantly upregulated in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. linc00665 affects the sensitivity of NSCLC cells to the chemotherapy drug cisplatin (DDP), making it a potential target for the treatment of NSCLC. Functional experiments showed that linc00665 enhanced the proliferation and migration of NSCLC cells in vivo and in vitro, and knocking down linc00665 could enhance the drug sensitivity of NSCLC cells to DDP. Further work revealed that linc00665 could recruit enhancer of zeste homolog 2 (EZH2) to the promoter region of cyclin-dependent kinase inhibitor 1C (CDKN1C) to inhibit its transcription and thus carry out its tumorigenic role. In conclusion, our study elucidated the carcinogenic role of the linc00665-EZH2-CDKN1C axis in NSCLC tumors and its ability to influence the sensitivity of these tumors to DDP. These results suggest that linc00665 may be a potential diagnostic marker and therapeutic target in NSCLC, and they also provide a new direction for the development of clinical reversal methods for acquired drug resistance in patients with NSCLC.
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Comprehensive Analysis of lncRNAs Related to the Prognosis of Esophageal Cancer Based on ceRNA Network and Cox Regression Model. BIOMED RESEARCH INTERNATIONAL 2021; 2020:3075729. [PMID: 33381546 PMCID: PMC7748909 DOI: 10.1155/2020/3075729] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/15/2020] [Accepted: 11/21/2020] [Indexed: 01/10/2023]
Abstract
Background Esophageal cancer is one of the most deadly malignant tumors. Among the common malignant tumors in the world, esophageal cancer is ranked seventh, which has a high mortality rate. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. lncRNAs can competitively bind microRNAs (miRNAs) with mRNA, which can regulate the expression level of the encoded gene at the posttranscriptional level. This regulatory mechanism is called the competitive endogenous RNA (ceRNA) hypothesis, and ceRNA has important research value in tumor-related research. However, the regulation of lncRNAs is less studied in the study of esophageal cancer. Methods The Cancer Genome Atlas (TCGA) database was used to download transcriptome profiling data of esophageal cancer. Gene expression quantification data contains 160 cancer samples and 11 normal samples. These data were used to identify differentially expressed lncRNAs and mRNAs. miRNA expression data includes 185 cancer samples and 13 normal samples. The differentially expressed RNAs were identified using the edgeR package in R software. Then, the miRcode database was used to predict miRNAs that bind to lncRNAs. MiRTarBase, miRDB, and TargetScan databases were used to predict the target genes of miRNAs. Cytoscape software was used to draw ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using DAVID 6.8. Finally, multifactor cox regression was used to screen lncRNAs related to prognosis. Results We have screened 1331 DElncRNAs, 3193 DEmRNAs, and 162 DEmiRNAs. Among them, the ceRNA network contains 111 lncRNAs, 11 miRNAs, and 63 DEmRNAs. Finally, we established a prediction model containing three lncRNAs through multifactor Cox regression analysis. Conclusions Our research screened out three independent prognostic lncRNAs from the ceRNA network and constructed a risk assessment model. This is helpful to understand the regulatory role of lncRNAs in esophageal cancer.
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Li M, Liang M, Lan T, Wu X, Xie W, Wang T, Chen Z, Shen S, Peng B. Four Immune-Related Long Non-coding RNAs for Prognosis Prediction in Patients With Hepatocellular Carcinoma. Front Mol Biosci 2020; 7:566491. [PMID: 33364253 PMCID: PMC7752774 DOI: 10.3389/fmolb.2020.566491] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 10/23/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Long non-coding RNA (LncRNA) plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). This study aims to establish an immune-related LncRNA model for risk assessment and prognosis prediction in HCC patients. METHODS Hepatocellular carcinoma patient samples with complete clinical data and corresponding whole transcriptome expression were obtained from the Cancer Genome Atlas (TCGA). Immune-related genes were acquired from the Gene Set Enrichment Analysis (GSEA) website and matched with LncRNA in the TCGA to get immune-related LncRNA. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for screening the candidate LncRNAs and calculating the risk coefficient to establish the prognosis model. Patients were divided into a high-risk group and a low-risk group depending on the median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort. GSEA and principal component analysis were used for function evaluation. RESULTS A total of 319 samples met the screening criteria and were randomly distributed across the training cohort and the validation cohort. After comparison with the IMMUNE_RESPONSE gene set and the IMMUNE_SYSTEM_PROCESS gene set, a total of 3094 immune-related LncRNAs were screened. Ultimately, four immune-related LncRNAs were used to construct a formula using LASSO regression. According to the formula, the low-risk group showed a higher survival rate than the high-risk group in the validation cohort and the whole cohort. The receiver operating characteristic curves data demonstrated that the risk score was more specific than other traditional clinical characteristics in predicting the 5-year survival rate for HCC. CONCLUSION The four-immune-related-LncRNA model can be used for survival prediction in HCC and guide clinical therapy.
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Affiliation(s)
- Muqi Li
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minni Liang
- Center of Surgery and Anaesthiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Tian Lan
- Department of Pancreatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiwen Wu
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wenxuan Xie
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Tielong Wang
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Zhitao Chen
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Shunli Shen
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Baogang Peng
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Lian W, Jiang X, Li L, Wang Q, Hong C, Yang P, Chen D. Upregulated Long Non-Coding RNA LL22NC03-N64E9.1 Promotes the Proliferation and Migration of Human Breast Cancer Cells by Silencing Kruppel-Like Factor 2 Expression. Cancer Manag Res 2020; 12:10763-10770. [PMID: 33149681 PMCID: PMC7605590 DOI: 10.2147/cmar.s268725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 10/05/2020] [Indexed: 12/11/2022] Open
Abstract
Introduction Recently, the significant regulatory effects of lncRNAs on the oncogenesis and growth of tumor have been demonstrated by an increasing number of research projects. A previous study showed that LL22NC03-N64E9.1 could promote the development of colorectal cancer, especially via enhanced cell proliferation. Similarly, this lncRNA should have comparable functions in breast cancer (BC), which requires in-depth investigation. Therefore, this study was designed to explore the correlation of LL22NC03-N64E9.1 with BC. Methods qRT-PCR was used to assess the relative expression of LL22NC03-N64E9.1 in BC tissues. Cell viability examination and colony formation experiments were performed to investigate the role of LL22NC03-N64E9.1 in BC cell’s proliferation. Transwell assays were used to explore the effects of LL22NC03-N64E9.1 on BC cell’s migration. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of LL22NC03-N64E9.1 with target proteins and genes in BC cells. Results We identified that LL22NC03-N64E9.1 is an oncogene, upregulated in BC, which was verified in a cohort of 48 pairs of BC tissues. Based on the loss-of-function experiments, silencing LL22NC03-N64E9.1 expression significantly inhibited malignancy progression. In terms of the mechanism, LL22NC03-N64E9.1 acted on the enhancer of zeste homolog 2 (EZH2) by direct binding, which promoted BC cell growth. Furthermore, in the promoters of KLF2, the trimethylation of H3K27 could be regulated by LL22NC03-N64E9.1 as the mediator. Conclusion Relying on the LL22NC03-N64E9.1/EZH2/KLF2 pathway, the lncRNA LL22NC03-N64E9.1 was significantly associated with BC development and could, therefore, be a potential therapeutic target to block BC growth.
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Affiliation(s)
- Weibin Lian
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People's Republic of China
| | - Xiaohua Jiang
- Department of Orthopedics, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, People's Republic of China
| | - Liangqiang Li
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People's Republic of China
| | - Qinglan Wang
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People's Republic of China
| | - Chengye Hong
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People's Republic of China
| | - Peidong Yang
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People's Republic of China
| | - Debo Chen
- Department of Breast Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People's Republic of China
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Ge S, Mi Y, Zhao X, Hu Q, Guo Y, Zhong F, Zhang Y, Xia G, Sun C. Characterization and validation of long noncoding RNAs as new candidates in prostate cancer. Cancer Cell Int 2020; 20:531. [PMID: 33292248 PMCID: PMC7603695 DOI: 10.1186/s12935-020-01615-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 10/20/2020] [Indexed: 12/19/2022] Open
Abstract
Background Long noncoding RNAs (lncRNAs) have been proved to be an important regulator in gene expression. In almost all kinds of cancers, lncRNAs participated in the process of pathogenesis, invasion, and metastasis. Meanwhile, compared with the large amounts of patients, there is rare knowledge about the role of lncRNAs in prostate cancer (PCa). Material/Method In this study, lncRNA expression profiles of prostate cancer were detected by Agilent microarray chip, 5 pairs of case and control specimens were involved in. Differentially expressed lncRNAs were screened out by volcano plot for constructing lncRNA-miRNA-mRNA central network. Then, the top ten up-regulated and down-regulated lncRNAs were validated by qRT-PCR in another 5 tumor specimens and 7 para-cancerous/benign contrasts. Furthermore, we searched for the survival curve of the top 10 upregulated and downregulated lncRNAs. Results A total of 817 differentially expressed lncRNAs were filtered out by the criteria of fold change (FC) and t-test p < 0.05. Among them, 422 were upregulated, whereas 395 were downregulated in PCa tissues. Gene ontology and KEGG pathway analyses showed that many lncRNAs were implicated in carcinogenesis. lnc-MYL2-4:1 (FC = 0.00141, p = 0.01909) and NR_125857 (FC = 59.27658, p = 0.00128) had the highest magnitude of change. The subsequent qPCR confirmed the expression of NR_125857 was in accordance with the clinical samples. High expression of PCA3, PCAT14 and AP001610.9 led to high hazard ratio while low expression of RP11-279F6.2 led to high hazard ratio. Conclusions Our study detected a relatively novel complicated map of lncRNAs in PCa, which may have the potential to investigate for diagnosis, treatment and follow-up in PCa. Our study revealed the expression of NR_125857 in human PCa tissues was most up-regulated. Further studies are needed to investigate to figure out the mechanisms in PCa.
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Affiliation(s)
- Shengyang Ge
- Department of Urology, Huashan Hospital, Fudan University, 12 Central Urumqi Rd, Shanghai, 200040, P. R. China
| | - Yuanyuan Mi
- Department of Urology, Affiliated Hospital of Jiangnan University, Hefeng Rd, Wuxi, 214000, PR China
| | - Xiaojun Zhao
- Department of Clinical Immunology, Shanghai Center for Clinical Laboratory, 528 Hongshan Rd, Shanghai, 200126, P. R. China
| | - Qingfeng Hu
- Department of Urology, Huashan Hospital, Fudan University, 12 Central Urumqi Rd, Shanghai, 200040, P. R. China
| | - Yijun Guo
- Department of Urology, Jing'an District Central Hospital, Fudan University, 259 Xikang Rd, Shanghai, 200040, P. R. China
| | - Fan Zhong
- Department of Systems Biology for Medicine, and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 130 Dongan Rd, Shanghai, P. R. China
| | - Yang Zhang
- Department of Systems Biology for Medicine, and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 130 Dongan Rd, Shanghai, P. R. China
| | - Guowei Xia
- Department of Urology, Huashan Hospital, Fudan University, 12 Central Urumqi Rd, Shanghai, 200040, P. R. China.
| | - Chuanyu Sun
- Department of Urology, Huashan Hospital, Fudan University, 12 Central Urumqi Rd, Shanghai, 200040, P. R. China.
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Li J, Wu X, Cao W, Zhao J. Long non-coding RNA NCK1-AS1 promotes the proliferation, migration and invasion of non-small cell lung cancer cells by acting as a ceRNA of miR-137. Am J Transl Res 2020; 12:6908-6920. [PMID: 33194081 PMCID: PMC7653585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 09/30/2020] [Indexed: 06/11/2023]
Abstract
Long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis and progression. In this study, we mainly investigate the potential influence of lncRNA NCK1 antisense RNA 1 (NCK1-AS1) on the progression of non-small cell lung cancer (NSCLC). RT-PCR was performed to determine the expression of NCK1-AS1 and miR-137 in NSCLC specimens and cell lines. The clinical significance of NCK1-AS1 in 148 patients was analyzed statistically. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of NCK1-AS1 and miR-137. Regulatory effects of NCK1-AS1 on proliferative, colony formation abilities, metastasis and apoptosis of SK-MES-1 and H1299 cells were assessed through a series of functional experiments. RNA-pull down and Dual-Luciferase reporter assay was performed to verify the sponge effect of NCK1-AS1 on miR-137. We observed that NCK1-AS1 expression was upregulated, while miR-137 expression was down-regulated in NSCLC specimens and cell lines. Increased NCK1-AS1 expression was positively correlated with TNM stage and lymph node metastasis and poor clinical outcome. The diagnostic value of NCK1-AS1 and miR-137 expression was also confirmed. Functionally, knockdown of NCK1-AS1 suppressed the proliferation, migration and invasion of NSCLC cells, and promoted apoptosis. Moreover, NCK1-AS1 was able to adsorb miR-137 via a sponge effect. Overall, our findings suggested that NCK1-AS1 may be a candidate biomarker and a target for new therapies in NSCLC patients.
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Affiliation(s)
- Jianxin Li
- Department of Clinical Laboratory, Rizhao Hospital of Traditional Chinese MedicineRizhao City, Shandong Province, China
| | - Xinglong Wu
- Department of Clinical Laboratory, Lanling People’s HospitalLinyi City, Shandong Province, China
| | - Wenxia Cao
- Department of Clinical Laboratory, Anqiu Women and Children’s HospitalAnqiu City, Shandong Province, China
| | - Jianqiang Zhao
- Department of Clinical Laboratory, Weifang People’s HospitalWeifang City, Shandong Province, China
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She JK, Fu DN, Zhen D, Gong GH, Zhang B. LINC01087 is Highly Expressed in Breast Cancer and Regulates the Malignant Behavior of Cancer Cells Through miR-335-5p/Rock1. Onco Targets Ther 2020; 13:9771-9783. [PMID: 33061456 PMCID: PMC7533226 DOI: 10.2147/ott.s255994] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 08/14/2020] [Indexed: 12/19/2022] Open
Abstract
PURPOSE Long non-coding RNA is involved in the genesis and development of various tumors, and it has been found through database screening that LINC01087 is highly expressed in breast cancer (BC), but mechanisms of LINC01087 in BC are still under investigation. Therefore, this study aimed to study relevant mechanisms of LINC01087 in BC to provide potential therapeutic targets for the disease in clinic practice. PATIENTS AND METHODS The qRT-PCR assay was applied to determine the LINC01087 expression in BC, and the cell counting kit-8 (CCK8) assay, transwell assay, and flow cytometry were used to analyze the proliferation, apoptosis, and invasion of breast cancer cells (BCCs), respectively. The Western blot assay was used to determine the ROCK1 expression, and the luciferase reporter gene assay, RNA-binding protein immunoprecipitation (RIP), and RNA pull-down assays were applied to study the interaction between LINC01087 and miR-335-5p. Moreover, tumor xenotransplantation was conducted in nude mice to explore the effects of LINC01087 on BCCs. RESULTS The qRT-PCR assay revealed that the LINC01087 expression in BC tissues was higher than that in corresponding tumor-adjacent tissues, and survival analysis revealed an unfavorable prognosis of patients with high expression of LINC01087. Down-regulation of LINC01087 could slow down the proliferation, invasion, and migration of BCCs and accelerate apoptosis of them in vitro. Luciferase reporter gene assay results revealed that LINC01087 enhanced the expression of ROCK1 by regulating miR-335-5p, and LINC01087 could be adopted as a miR-335-5p sponge to inhibit ROCK1 expression. CONCLUSION LINC01087 is overexpressed in cases with BC, and patients with high expression of it suffer a poor survival. Furthermore, LINC01087 can act as a miR-335-5p sponge to affect the expression of ROCK1 and affect the invasion and migration of BCCs.
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Affiliation(s)
- Ji-Kai She
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, People’s Republic of China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, People’s Republic of China
| | - Dan-Ni Fu
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, People’s Republic of China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, People’s Republic of China
| | - Dong Zhen
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, People’s Republic of China
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, People’s Republic of China
| | - Guo-Hua Gong
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, People’s Republic of China
- First Clinical Medical of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, People’s Republic of China
| | - Bin Zhang
- Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, People’s Republic of China
- First Clinical Medical of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, People’s Republic of China
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Wan S, Zhao H. Analysis of diagnostic and prognostic value of lncRNA MEG3 in cervical cancer. Oncol Lett 2020; 20:183. [PMID: 32934750 DOI: 10.3892/ol.2020.12044] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 05/06/2020] [Indexed: 02/06/2023] Open
Abstract
The present study aimed to explore the diagnostic and prognostic value of lncRNA maternally expressed 3 (MEG3) in cervical cancer. Eighty-four patients with cervical cancer from February 2013 to March 2014 were enrolled in the observation group (OG), and another 58 female subjects who underwent physical examination at Huangshi Central Hospital were enrolled as the control group (CG). The serum MEG3 expression of patients in the two groups was detected by RT-qPCR, and the ability of MEG3 to aid in the diagnosis of cervical cancer, lymph node metastasis and FIGO staging, as well as to predict mortality was evaluated by ROC curve. In addition, the patients in the OG were divided into high- and low-expression groups according to the median value of MEG3. Kaplan Meier was employed to analyze the survival status, and Cox regression to analyze the independent prognostic factors of cervical cancer patients. The results of the present study revealed that the serum MEG3 expression in the OG was significantly lower than that of the CG (P<0.05). The area under the curve (AUC) of MEG3 in diagnosing cervical cancer was 0.844, the AUC in predicting mortality was 0.858, while that in diagnosing lymph node transfer was 0.707, and that in diagnosing FIGO staging was 0.791. The 5-year survival rate of the high-expression group was higher than that of the low-expression group (P=0.020). Multivariate analysis indicated that MEG3 (HR, 0.173; 95 CI%, 0.028-0.919), lymph node metastasis (HR, 2.259; 95 CI%, 1.004-5.025) and FIGO staging (HR, 0.008; 95 CI%, 1.453-6.248) were independent prognostic factors for cervical cancer patients. Collectively, lncRNA MEG3 may be a diagnostic marker and prognostic indicator for cervical cancer, and has a certain diagnostic value for lymph node metastasis and FIGO staging. Lymph node metastasis, FIGO stage III and IV, and low MEG3 levels were revealed to be independent prognostic factors for cervical cancer patients.
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Affiliation(s)
- Shuqiong Wan
- Department of Obstetrics and Gynecology, Huangshi Central Hospital, Huangshi, Hubei 435000, P.R. China
| | - Huanqiu Zhao
- Department of Gynecology, Huangshi Maternity and Children's Health Hospital, Huangshi, Hubei 435000, P.R. China
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Zhang W, Liu K, Pei Y, Tan J, Ma J, Zhao J. Long Noncoding RNA HIF1A-AS2 Promotes Non-Small Cell Lung Cancer Progression by the miR-153-5p/S100A14 Axis. Onco Targets Ther 2020; 13:8715-8722. [PMID: 32922043 PMCID: PMC7457835 DOI: 10.2147/ott.s262293] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 08/04/2020] [Indexed: 12/17/2022] Open
Abstract
Background Long noncoding RNA (lncRNA) plays a critical role in initiating lung cancer. This study aims to research the function and mechanism of lncRNA HIF1A-AS2 in regulating non-small cell lung cancer (NSCLC) progression. Methods qRT-PCR was used to analyze gene expression. The CCK-8 assay was performed to detect cell proliferation. The Transwell assay was conducted to examine cell migration and invasion. A Caspase3 activity detection kit was utilized to analyze apoptosis. The luciferase reporter assay was carried out to research interactions of HIF1A-AS2, miR-153-5p and S100A14. Results HIF1A-AS2 expression was raised in NSCLC tissues and cell lines. The HIF1A-AS2 level was increased in advanced NSCLC tumor tissues. High HIF1A-AS2 expression was related to poor prognosis. HIF1A-AS2 knockdown decreased proliferation, migration and invasion while promoting apoptosis. HIF1A-AS2 was the sponge for miR-153-5p, and miR-153-5p targeted S100A14. HIF1A-AS2 promoted S100A14 expression through regulating miR-153-5p. Conclusion The HIF1A-AS2/miR-153-5p/S100A14 axis plays a crucial role in promoting NSCLC progression.
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Affiliation(s)
- Weiqiang Zhang
- Department of Thoracic Surgery, The 7th Medical Center of PLA General Hospital, Beijing 100700, People's Republic of China
| | - Keqiang Liu
- Department of Thoracic Surgery, The 7th Medical Center of PLA General Hospital, Beijing 100700, People's Republic of China
| | - Yingxin Pei
- Department of Thoracic Surgery, The 7th Medical Center of PLA General Hospital, Beijing 100700, People's Republic of China
| | - Jian Tan
- Department of Thoracic Surgery, The 7th Medical Center of PLA General Hospital, Beijing 100700, People's Republic of China
| | - Jingbo Ma
- Department of Thoracic Surgery, The 7th Medical Center of PLA General Hospital, Beijing 100700, People's Republic of China
| | - Jing Zhao
- Department of Thoracic Surgery, The 7th Medical Center of PLA General Hospital, Beijing 100700, People's Republic of China
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Ning Y, Bai Z. DSCAM-AS1 accelerates cell proliferation and migration in osteosarcoma through miR-186-5p/GPRC5A signaling. Cancer Biomark 2020; 30:29-39. [PMID: 32865178 DOI: 10.3233/cbm-190703] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Osteosarcoma (OS) is one of the most primary bone malignancies, often occurring in adolescents or children. Numerous scientific findings have introduced that long noncoding RNAs (lncRNAs) can be involved in tumor occurrence and development. Although DSCAM-AS1 has been studied in several cancers, its role and mechanism in OS are poorly understood. In this work, high level of DSCAM-AS1 was validated in OS cell lines. Depleting DSCAM-AS1 inhibited cell proliferation, migration and EMT process in OS. Subsequently, we disclosed that DSCAM-AS1 was mainly observed in the cytoplasm of OS cells and could bind with miR-186-5p in OS. Moreover, inhibiting miR-186-5p rescued the impact of silenced DSCAM-AS1 on OS progression. Additionally, GPRC5A was verified as the target downstream of miR-186-5p, and it was negatively modulated by miR-186-5p but positively regulated by DSCAM-AS1. More importantly, DSCAM-AS1 enhanced GPRC5A level in OS by sequestering miR-186-5p. Finally, up-regulating GPRC5A reversed the influences of DSCAM-AS1 repression on the oncogenic behaviors of OS cells. Knockdown of DSCAM-AS1 suppressed NPC tumor growth in vivo. All findings uncovered that DSCAM-AS1 aggravated OS progression through sponging miR-186-5p to up-regulate GPRC5A expression. Thus, we proposed DSCAM-AS1 as a probable target for OS treatment.
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Affiliation(s)
- Yuwen Ning
- Department of Health Administration and Medical Education in School of Military Preventive Medicine, The Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Zhengfa Bai
- Department of Orthopedics, The Fourth People's Hospital of Shaanxi, Xi'an, Shaanxi, China
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Wang T, Zhai R, Lv X, Wang K, Xu J. LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression. BMC Pulm Med 2020; 20:217. [PMID: 32795273 PMCID: PMC7427971 DOI: 10.1186/s12890-020-01229-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 07/08/2020] [Indexed: 12/12/2022] Open
Abstract
Background Lung adenocarcinoma (LAD) is a prevalent type of bronchogenic malignant tumor and one of the most critical factors related to human death. Long noncoding RNAs (lncRNAs) are involved in many complex biological processes and have been emerged as extremely important regulators of various cancers. LINC02418, a novel lncRNA, hasn’t been mentioned in previous studies on cancer development. Therefore, it’s important to define the potential function of LINC02418 in LAD. Methods Gene expression was examined by RT-qPCR or western blot. CCK-8, colony formation, TUNEL, and transwell assays were utilized to study the role of LINC02418 in LAD. The interaction of miR-4677-3p with LINC02418 (or KNL1) was verified through luciferase reporter, RIP and RNA pull-down assays. Results High expression of LINC02418 was observed in LAD specimens and cells. Downregulation of LINC02418 obstructed the proliferation and motility of LAD cells. Moreover, LINC02418 negatively modulated miR-4677-3p expression and miR-4677-3p overexpression could repress cell proliferation and migration. Moreover, kinetochore scaffold 1 (KNL1) expression was negatively modulated by miR-4677-3p but positively regulated by LINC02418. Furthermore, miR-4677-3p could bind with LINC02418 (or KNL1). Finally, KNL1 overexpression reversed the inhibitory function of LINC02418 deficiency in the malignant behaviors of LAD cells. Conclusions LINC02418 contributes to the malignancy in LAD via miR-4677-3p/KNL1 signaling, providing a probable therapeutic direction for LAD.
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Affiliation(s)
- Tao Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, Shaanxi, China
| | - Ruiren Zhai
- Department of Tumor Center, Sunshine Union Hospital, Weifang, 261000, Shandong, China
| | - Xiuhua Lv
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
| | - Ke Wang
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China
| | - Junqing Xu
- Department of Radiology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, No.1098 Xueyuan Avenue, Nanshan District, Shenzhen, 518055, Guangdong, China.
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Ding Y, Ding K, Gong W, Wei H, Mo W, Ding X. WITHDRAWN: Long non-coding RNA LUCAT1 up-regulates the expression of HIF-1α and promotes the proliferation and metastasis of breast cancer cells via sponging miR-199a-5p. Biomed J 2020. [DOI: 10.1016/j.bj.2020.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Lipsey CC, Harbuzariu A, Robey RW, Huff LM, Gottesman MM, Gonzalez-Perez RR. Leptin Signaling Affects Survival and Chemoresistance of Estrogen Receptor Negative Breast Cancer. Int J Mol Sci 2020; 21:E3794. [PMID: 32471192 PMCID: PMC7311967 DOI: 10.3390/ijms21113794] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/15/2020] [Accepted: 05/21/2020] [Indexed: 12/18/2022] Open
Abstract
Estrogen-receptor-negative breast cancer (BCER-) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER- progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER- patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER- patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER- patients. Targeting OBR signaling could improve chemotherapeutic efficacy.
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Affiliation(s)
- Crystal C. Lipsey
- Microbiology, Biochemistry, and Immunology, GEBS, Morehouse School of Medicine, Atlanta, GA 30310, USA; (C.C.L.); (A.H.)
- Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892, USA; (R.W.R.); (L.M.H.); (M.M.G.)
| | - Adriana Harbuzariu
- Microbiology, Biochemistry, and Immunology, GEBS, Morehouse School of Medicine, Atlanta, GA 30310, USA; (C.C.L.); (A.H.)
| | - Robert W. Robey
- Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892, USA; (R.W.R.); (L.M.H.); (M.M.G.)
| | - Lyn M. Huff
- Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892, USA; (R.W.R.); (L.M.H.); (M.M.G.)
| | - Michael M. Gottesman
- Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892, USA; (R.W.R.); (L.M.H.); (M.M.G.)
| | - Ruben R. Gonzalez-Perez
- Microbiology, Biochemistry, and Immunology, GEBS, Morehouse School of Medicine, Atlanta, GA 30310, USA; (C.C.L.); (A.H.)
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Zheng Z, Li X, You H, Zheng X, Ruan X. LncRNA SOCS2-AS1 inhibits progression and metastasis of colorectal cancer through stabilizing SOCS2 and sponging miR-1264. Aging (Albany NY) 2020; 12:10517-10526. [PMID: 32437330 PMCID: PMC7346041 DOI: 10.18632/aging.103276] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 04/20/2020] [Indexed: 12/12/2022]
Abstract
Abnormal expression of long noncoding RNA (lncRNA) is involved in human cancers, including colorectal cancer (CRC). However, their functional mechanism is largely unknown. In this study, we explored the roles of lncRNA SOCS2-AS1 in modulating CRC progression. We showed that SOCS2-AS1 was lowly expressed in CRC tissues and cells. SOCS2-AS1 downregulation predicted a poor prognosis in patients with CRC. SOCS2-AS1 overexpression significantly suppressed CRC cell proliferation, colony formation, EdU incorporation, cell-cycle, migration and invasion in vitro while SOCS2-AS1 knockdown led to an opposite phenotype. SOCS2-AS1 overexpression inhibited CRC growth and metastasis in vivo. Mechanistically, we discovered that SOCS2-AS1 was positively correlated with SOCS2 expression in CRC tissues. SOCS2-AS1 contributes to SOCS2 expression through restraining miR-1264. Additionally, we showed that SOCS2 silencing abrogated the suppressive effects of SOCS2-AS1 overexpression. Taken together, our results identified a novel regulatory loop in which SOCS2-AS1/miR-1264/SOCS2 axis suppresses CRC progression.
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Affiliation(s)
- Zhihai Zheng
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xiaoxiao Li
- Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Heyi You
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xiaofeng Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xiaojiao Ruan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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Wu Z, Wang YM, Dai Y, Chen LA. POLE2 Serves as a Prognostic Biomarker and Is Associated with Immune Infiltration in Squamous Cell Lung Cancer. Med Sci Monit 2020; 26:e921430. [PMID: 32304567 PMCID: PMC7191965 DOI: 10.12659/msm.921430] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Squamous cell lung cancer is the main cause of cancer-associated mortality. The discovery of promising prognostic biomarkers for predicting the survival of patients with squamous cell lung cancer remains a challenge. Material/Methods Gene expression profiles of GSE33479 and GSE51855, including 42 squamous cell lung cancer tissues and 17 normal tissues, from the GEO database were assessed to find common differentially expressed genes (DEGs) via the GEO2R online tool and Venn diagram software. Then, gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses were conducted. The key protein-protein interaction (PPI) network within those common DEGs was subsequently illustrated through a combination of Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape software. Finally, core genes associated with survival and levels of immune infiltration were demonstrated by the Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) online database, respectively. Results In total, 483 DEGs were involved, including 216 upregulated genes enriched in “cell division”, “DNA replication”, and “DNA repair pathway” and 267 downregulated genes enriched in “cell adhesion”, “oxidation-reduction process”, and “cell-cell signaling”. The 75 core genes were selected by Molecular Complex Detection applied in Cytoscape. Four genes – MND1, FOXM1, CDC6, and POLE2 – were found to be significantly associated with survival. Further analysis of the KEEG pathway and TIMER database revealed that only POLE2 was enriched in “DNA replication” and its higher expression was negatively associated with survival and immune infiltration. Conclusions Higher expression of POLE2 is a prognosis-related biomarker for worse survival and is negatively associated with immune infiltration in squamous cell lung cancer.
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Affiliation(s)
- Zhen Wu
- Respiratory Department, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China (mainland)
| | - Yue-Ming Wang
- School of Medicine, Nankai University, Beijing, China (mainland)
| | - Yu Dai
- Respiratory Department, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China (mainland)
| | - Liang-An Chen
- Respiratory Department, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China (mainland).,School of Medicine, Nankai University, Beijing, China (mainland)
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Feng S, Liu N, Chen X, Liu Y, An J. Long non-coding RNA NEAT1/miR-338-3p axis impedes the progression of acute myeloid leukemia via regulating CREBRF. Cancer Cell Int 2020; 20:112. [PMID: 32280304 PMCID: PMC7137299 DOI: 10.1186/s12935-020-01182-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 03/23/2020] [Indexed: 02/07/2023] Open
Abstract
Background Acute myeloid leukemia (AML) is a heterogeneous hematological disease. Our purpose of the research was to investigate the regulatory influence of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1)/microRNA-338-3p (miR-338-3p)/CREB3 regulatory factor (CREBRF) in AML progression. Methods The associated RNA and protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell growth was assessed through colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometry was exploited to determine the apoptosis rate. Cell migration and invasion were detected by transwell assay. The combination of miR-338-3p and NEAT1 or CREBRF was analyzed via the dual-luciferase reporter assay. Results NEAT1 and CREBRF were down-regulated in AML tissues and cells. NEAT1 up-regulation suppressed cell growth, migration and invasion but enhanced apoptosis of AML cells. Inhibition of CREBRF reverted the NEAT1-induced effects on AML cells. Moreover, NEAT1 directly targeted miR-338-3p and miR-338-3p targeted CREBRF. NEAT1/miR-338-3p could affect cellular behaviors of AML cells via the modulation of CREBRF. Conclusion NEAT1/miR-338-3p axis repressed the AML progression through regulating CREBRF, which might afford a favorable perspective for the AML treatment molecularly.
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Affiliation(s)
- Song Feng
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Na Liu
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Xiaoguang Chen
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Yufeng Liu
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
| | - Jindou An
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052 Henan China
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Sun Y, Niu X, Wang G, Qiao X, Chen L, Zhong M. A Novel lncRNA ENST00000512916 Facilitates Cell Proliferation, Migration and Cell Cycle Progression in Ameloblastoma. Onco Targets Ther 2020; 13:1519-1531. [PMID: 32110049 PMCID: PMC7037065 DOI: 10.2147/ott.s236158] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 02/04/2020] [Indexed: 12/12/2022] Open
Abstract
Objective Our purpose was to identify up-regulated long noncoding RNA ENST00000512916 in ameloblastoma (AB) and explore its role in the progression of AB. Methods We analyzed lncRNA microarray expression profile between six paired AB and normal oral mucosa (NOM) tissues. An up-regulated lncRNA, ENST00000512916 was identified and validated by real-time qPCR. Cell proliferation, migration and cell cycle were detected by CCK-8 assay, transwell chamber and flow cytometry, respectively. Western blotting analysis was used to measure the expression of cell-cycle-related proteins including CyclinD1 and Cyclin-dependent kinase (CDK) 2/4/6. In addition, Xenograft tumor model was constructed to investigate tumor growth. Results Real-time qPCR confirmed that lncRNA ENST00000512916 was up-regulated in AB tissues. ENST00000512916 knockdown significantly inhibited cell proliferation, migration and the expression of CDK2/4/6 in AM-1 cells. Moreover, ENST00000512916 knockdown suppressed tumor growth in vivo. We also found that ENST00000512916 overexpression significantly promoted the expression of HOXC13 in AM-1 cells. Overexpression of ENST00000512916 promoted cell cycle progression in AM-1 cells, which was reversed by HOXC13 knockdown. Conclusion Our findings reveal that lncRNA ENST00000512916 promotes cell proliferation, migration and cell cycle progression of AB.
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Affiliation(s)
- Yan Sun
- Department of Oral Histopathology, School of Stomatology, China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Xing Niu
- Department of Oral Histopathology, School of Stomatology, China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Guannan Wang
- Department of Oral Histopathology, School of Stomatology, China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Xue Qiao
- Department of Central Laboratory, School of Stomatology, China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Lijie Chen
- Department of Oral Histopathology, School of Stomatology, China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Ming Zhong
- Department of Oral Histopathology, School of Stomatology, China Medical University, Shenyang, Liaoning, People's Republic of China
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Guo L, Lu J, Gao J, Li M, Wang H, Zhan X. The function of SNHG7/miR-449a/ACSL1 axis in thyroid cancer. J Cell Biochem 2020; 121:4034-4042. [PMID: 31961004 DOI: 10.1002/jcb.29569] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 12/09/2019] [Indexed: 12/12/2022]
Abstract
Thyroid cancer (TC) has been characterized as the most common malignant malady of the endocrine system. Small nucleolar RNA host gene 7 (SNHG7) has been reported to serve as a key regulator in a large number of human cancer types, but its role in TC and the underlying regulatory mechanism have never been evaluated yet. The present study indicated that the expression of SNHG7 was markedly higher in TC cell lines. Knockdown of SNHG7 led to a suppression of TC cell progression and migration. Acyl-CoA synthetase long-chain family member 1 (ACSL1) has also been demonstrated as an oncogene in many cancers. Herein an inhibition of ACSL1 after SNHG7 knockdown was captured. Further, the suppressing effects of SNHG7 knockdown on TC cell processes were counteracted by ACSL1 overexpression. Data from online bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays validated the interaction between microRNA-449a (miR-449a) and SNHG7 or ACSL1. It was also verified that SNHG7 sequestered miR-449a and therefore elevated ACSL1 expression levels. To conclude, the current study indicated that SNHG7 promoted proliferation and migration of TC cells by sponging miR-449a and therefore upregulating ACSL1. The present study may provide more explorations about the molecular regulation mechanism of long noncoding RNAs in TC progression.
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Affiliation(s)
- Linchi Guo
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.,General Medicine, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia, China
| | - Jixuan Lu
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.,General Medicine, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia, China
| | - Jie Gao
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.,General Medicine, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia, China
| | - Mingyang Li
- Department of Endocrinology, Affiliated Hospital of Chifeng Medical College, Chifeng, Inner Mongolia, China
| | - Huihui Wang
- Department of Endocrinology, Qiqihar First Hospital, Qiqihar, Heilongjiang, China
| | - Xiaorong Zhan
- Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Chen WJ, Xiong L, Yang L, Yang LJ, Li L, Huang L, Liang XQ, Xue J, Tan BZ. Long Non-Coding RNA LINC01783 Promotes the Progression of Cervical Cancer by Sponging miR-199b-5p to Mediate GBP1 Expression. Cancer Manag Res 2020; 12:363-373. [PMID: 32021449 PMCID: PMC6972596 DOI: 10.2147/cmar.s230171] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Accepted: 11/01/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Long non-coding RNA showed potential regulating effects in oncogenesis. Highly expressed LncRNA LINC01783 is observed in cervical cancer. However, the specific pathogenesis of cervical cancer is still unclear. METHODS Differential lncRNAs in cervical cancer were identified based on TCGA dataset. Subsequently, qRT-PCR was utilized for testing the LINC01783 expression in cervical cancer cell lines and normal human cervical epithelial cell line HcerEpic. CCK-8, EdU, Wound healing assay, Transwell assay and flow cytometry were used for detecting proliferative and migratory potential, cell cycle and apoptosis of cervical cancer cells, respectively. To identify the potential target of LINC01783, bioinformatics assay and dual-luciferase reporter gene assay were performed. Moreover, to clarify their interactions and roles in regulating the progression of cervical cancer, Western blot assay and RIP assay were carried out. RESULTS Our results revealed LINC01783 is overexpressed in cervical cancer cells. Overexpressed LINC01783 considerably accelerated the cell proliferation, migration and invasion of cervical cancer cells while restrained cell apoptosis of them. Moreover, LINC01783 positively regulated the GBP1 expression via competitively binding to miR-199b-5p. CONCLUSION LINC01783 is involved in the progression of cervical cancer through competitively binding to miR-199b-5p to mediate GBP1 expression.
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Affiliation(s)
- Wei-jun Chen
- Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Nanchang University, Reproductive Hospital Affiliated to Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China
| | - Liang Xiong
- Department of Urinary Surgery, Armed Police Jiangxi General Team Hospital, Nanchang, Jiangxi, People’s Republic of China
| | - Lin Yang
- Department of Reproductive Medicine, Reproductive Hospital Affiliated to Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China
| | - Li-juan Yang
- Department of Reproductive Medicine, Reproductive Hospital Affiliated to Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China
| | - Lin Li
- Department of Reproductive Medicine, Reproductive Hospital Affiliated to Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China
| | - Li Huang
- Department of Reproductive Medicine, Reproductive Hospital Affiliated to Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China
| | - Xiao-qing Liang
- Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China
| | - Jie Xue
- Department of Reproductive Medicine, Reproductive Hospital Affiliated to Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China
| | - Bu-zhen Tan
- Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China
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Gao Z, Fu P, Yu Z, Zhen F, Gu Y. Comprehensive Analysis of lncRNA-miRNA- mRNA Network Ascertains Prognostic Factors in Patients with Colon Cancer. Technol Cancer Res Treat 2019; 18:1533033819853237. [PMID: 31159706 PMCID: PMC6552362 DOI: 10.1177/1533033819853237] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background: Non-coding RNAs are competing endogenous RNAs in the occurrence and development of tumorigenesis; numerous microRNAs are aberrantly expressed in colon cancer tissues and play significant roles in oncogenesis development and metastasis. However, large clinical and RNA data are lacking to further confirm the exact role of these RNAs in tumors. This study aimed to ascertain differential RNA expression between colon cancer and normal colon tissues. Materials and Methods: RNA sequencing and clinical data of patients with colon cancer were procured from The Cancer Genome Atlas database; differentially expressed long non-coding RNA, differentially expressed messenger RNAs, and differentially expressed microRNAs were achieved using the limma package in edgeR to generate competing endogenous RNAs networks. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted with ggplot2 package, the Kaplan-Meier survival method was used to predict survival in patients with colon cancer. Results: In total, 1174 differentially expressed long non-coding RNAs, 2068 differentially expressed messenger RNAs, and 239 differentially expressed microRNAs were generated between 480 colon cancer and 41 normal colon tissue samples. Three competing endogenous RNA networks were established. Gene Ontology analysis indicated that the genes of the up-regulated microRNA network were involved in negative regulation of transcription, DNA-template, and those of down-regulated microRNA network were involved in transforming growth factor β receptor signaling pathways, response to hypoxia, cell migration, while Kyoto Encyclopedia of Genes and Genomes analyses of these networks turned out to be negative. Three long non-coding RNAs (AP004609.1, ARHGEF26-AS1, and LINC00491), 3 microRNAs (miRNA-141, miRNA-216a, and miRNA-193b) and 3 RNAs (ULBP2, PHLPP2, and TPM2) were detected to be associated with prognosis by the Kaplan-Meier survival analysis. Additionally, univariate and multivariate Cox regression analyses showed that the microRNA-216a of the competing endogenous RNA might be an independent prognostic factor in colon cancer. Conclusions: This study constructed the non-coding RNA-related competing endogenous RNA networks in colon cancer and sheds lights on underlying biomarkers for colon cancer cohorts.
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Affiliation(s)
- Zhenzhen Gao
- 1 Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,2 Department of Bone Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Peng Fu
- 2 Department of Bone Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Zhengyi Yu
- 1 Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Fuxi Zhen
- 1 Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yanhong Gu
- 1 Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Li FZ, Zang WQ. Knockdown of lncRNAXLOC_001659 inhibits proliferation and invasion of esophageal squamous cell carcinoma cells. World J Gastroenterol 2019; 25:6299-6310. [PMID: 31754291 PMCID: PMC6861847 DOI: 10.3748/wjg.v25.i42.6299] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 09/27/2019] [Accepted: 11/01/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Studies have shown that long non-coding RNAs (lncRNAs) play a key role in almost all key physiological and pathological processes, including different types of malignant tumors. Our previous lncRNA microarray results have shown that lncRNA XLOC_001659 is upregulated in esophageal cancer (EC) tissues, with a fold change of 20.9 relative to normal esophageal tissues. But its effect and the molecular biological mechanisms on proliferation and invasion of EC cells remain unclear.
AIM To investigate the effect of lncRNA XLOC_001659 on esophageal squamous cell carcinoma (ESCC) cells and explore the molecular biological mechanisms involved.
METHODS RT-qPCR assay was used to quantify the expression levels of lncRNAXLOC-001659 and miR-490-5p. The proliferative capacity of the cells was determined using CCK8 and colony formation assays, and the effect of lncRNAXLOC-001659 on the invasion of ESCC cells was determined by Transwell assay. Dual-luciferase reporter assay was used to detect the target genes of lncRNAXLOC-001659 and miR-490-5p.
RESULTS The results of RT-qPCR showed that the expression of lncRNAXLOC_001659 was upregulated in ESCC cells. CCK-8 assay showed that knockdown of lncRNAXLOC_001659 significantly inhibited ESCC cell proliferation. Colony formation and Transwell invasion assays showed that knockdown of lncRNAXLOC_001659 or overexpression of miR-490-5p significantly inhibited ESCC cell growth and invasion. Furthermore, lncRNAXLOC_001659 acts as an endogenous sponge by competitively binding to miR-490-5p to downregulate miR-490-5p. Further results confirmed that miR-490-5p targeted PIK3CA, and the recovery of PIK3CA rescued lncRNAXLOC_001659 knockdown or miR-490-5p overexpression-mediated inhibition of cell proliferation and invasion, which suggested the presence of an lncRNAXLOC_001659/miR-490-5p/PIK3CA regulatory axis.
CONCLUSION Knockdown of lncRNA XLOC_001659 inhibits proliferation and invasion of ESCC cells via regulation of miR-490-5p/PIK3CA, suggesting that it may play a role in ESCC tumorigenesis and progression.
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Affiliation(s)
- Feng-Zhi Li
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Wen-Qiao Zang
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Liu C, Zhang H, Liu H. Long Noncoding RNA UCA1 Accelerates Nasopharyngeal Carcinoma Cell Progression By Modulating miR-124-3p/ITGB1 Axis. Onco Targets Ther 2019; 12:8455-8466. [PMID: 31632090 PMCID: PMC6793467 DOI: 10.2147/ott.s215819] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 09/05/2019] [Indexed: 12/12/2022] Open
Abstract
Background Nasopharyngeal carcinoma (NPC) is a common malignant cancer that is distributed particularly in Southeastern Asia. Previous studies have manifested that long noncoding RNA urothelial carcinoma associated 1 (UCA1) was involved in NPC tumorigenesis and metastasis. However, the biological mechanism of UCA1 for NPC cell progression requires further investigation. Methods The expression levels of UCA1, miR-124-3p, integrin beta-1 (ITGB1) were detected by qRT-PCR. Protein expression of ITGB1 was determined by Western blot assay. Cell proliferation, migration and invasion were evaluated by CCK8 and transwell assay, respectively. The interaction between miR-124-3p and UCA1 or ITGB1 was determined by luciferase reporter system, RIP and RNA pull-down assay. Mice model was established by subcutaneously injecting SUNE1 cells stably transfected with sh-UCA1 and sh-NC. Results The expression of UCA1 was up-regulated in NPC tissues and cells. However, UCA1 knockdown hindered NPC cell growth, migration and invasion. In addition, the interaction between miR-124-3p and UCA1 or ITGB1 was confirmed by luciferase reporter system, RIP and RNA pull-down assay. Besides, miR-124-3p inhibitor abrogated UCA1 silencing-mediated suppression on cell progression in NPC. Moreover, UCA1 accelerated NPC cell progression through modulating ITGB1 via sponging miR-124-3p. In vivo experiments revealed the interference of UCA1-inhibited tumor growth by regulating miR-124-3p/ITGB1 axis. Conclusion UCA1 acts as an oncogene to promote NPC cell proliferation by up-regulating ITGB1 through suppressing miR-124-3p in vitro and in vivo, providing a potential target for NPC diagnosis and treatment.
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Affiliation(s)
- Chunxiu Liu
- Department of Otolaryngology, Jining First People's Hospital of Shandong Province, Jinning 272000, People's Republic of China
| | - Hu Zhang
- Department of ENT, Zhangqiu District People's Hospital, Jinan 250200, People's Republic of China
| | - Hui Liu
- Department of Otolaryngology, Jining First People's Hospital of Shandong Province, Jinning 272000, People's Republic of China
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Wang N, Wang J, Meng X, Li T, Wang S, Bao Y. The Pharmacological Effects of Spatholobi Caulis Tannin in Cervical Cancer and Its Precise Therapeutic Effect on Related circRNA. Mol Ther Oncolytics 2019; 14:121-129. [PMID: 31194163 PMCID: PMC6551555 DOI: 10.1016/j.omto.2019.04.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 04/30/2019] [Indexed: 12/12/2022] Open
Abstract
The chemical components of Spatholobi Caulis tannin (SCT) have a modest therapeutic effect in patients with cervical cancer. However, the active components and the mechanism of action of SCT in HeLa cervical cancer cells need to be further studied. In this paper, 3D microfluidic chip technology was applied to simulate the effects of tannins in the human body, and the appropriate dose and time of administration were calculated. The cell cycle and apoptosis experiments demonstrated that SCT inhibits proliferation and stimulated apoptosis in HeLa cells. The differentially expressed genes were screened using The Cancer Genome Atlas (TCGA) and the GEO databases to identify common differentially expressed genes. A bioinformatic analysis of relevant genes, analysis using the molecular docking technique, and survival analysis were used to predict the target genes of SCT. Circular RNAs (circRNAs) associated with the SCT target genes and the regulatory effects of SCT on these circRNAs were determined. These studies showed that SCT mediates related circRNAs in HeLa cells to inhibit proliferation and promote apoptosis in HeLa cells. Thus, SCT may be an effective strategy for treating cervical cancer.
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Affiliation(s)
- Nijia Wang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, P.R. China
| | - Jiayi Wang
- Liaoning Institute for Drug Control, Shenyang 110036, P.R. China
| | - Xiansheng Meng
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, P.R. China
- Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, P.R. China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, P.R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Laboratory, Dalian 116600, P.R. China
| | - Tianjiao Li
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, P.R. China
- Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, P.R. China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, P.R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Laboratory, Dalian 116600, P.R. China
| | - Shuai Wang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, P.R. China
- Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, P.R. China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, P.R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Laboratory, Dalian 116600, P.R. China
| | - Yongrui Bao
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, P.R. China
- Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, P.R. China
- Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian 116600, P.R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Laboratory, Dalian 116600, P.R. China
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Long noncoding RNA FGD5-AS1 promotes colorectal cancer cell proliferation, migration, and invasion through upregulating CDCA7 via sponging miR-302e. In Vitro Cell Dev Biol Anim 2019; 55:577-585. [DOI: 10.1007/s11626-019-00376-x] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 06/03/2019] [Indexed: 12/22/2022]
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Ma L, Sun X, Kuai W, Hu J, Yuan Y, Feng W, Lu X. LncRNA SOX2 overlapping transcript acts as a miRNA sponge to promote the proliferation and invasion of Ewing's sarcoma. Am J Transl Res 2019; 11:3841-3849. [PMID: 31312393 PMCID: PMC6614621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 05/17/2019] [Indexed: 06/10/2023]
Abstract
Long non-coding RNAs (lncRNAs) function as critical regulator in human cancers. However, the biological regulatory mechanisms of lncRNAs in Ewing's sarcoma are still elusive. This study tries to investigate the clinical significance and pathological role of lncRNA SOX2 overlapping transcript (SOX2OT) in Ewing's sarcoma progression. SOX2OT was identified to be up-regulated in Ewing's sarcoma tissue and cells. In vitro, SOX2OT knockdown suppressed Ewing's sarcoma cells proliferation and invasion, and triggered apoptosis. In vivo xenograft assays, SOX2OT knockdown significantly inhibited Ewing's sarcoma growth. With the help of bioinformatics analysis and luciferase assay, SOX2OT was validated to harbor miR-363, acting as miRNA sponge or competing endogenous RNA (ceRNA). Furthermore, FOXP4 was validated to be the target protein of miR-363. Western blot and RT-PCR confirmed that SOX2OT was positively correlated with FOXP4 protein via sponging miR-363, forming a negative cascade regulation. In conclusion, our study realizes that SOX2OT acted as oncogene in the tumorigenesis of Ewing's sarcoma, suggesting the SOX2OT/miR-363/FOXP4 pathway in Ewing's sarcoma.
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Affiliation(s)
- Li Ma
- Department of Pediatrics, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University Huaian 223300, China
| | - Xingzhen Sun
- Department of Pediatrics, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University Huaian 223300, China
| | - Wenxia Kuai
- Department of Pediatrics, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University Huaian 223300, China
| | - Jian Hu
- Department of Pediatrics, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University Huaian 223300, China
| | - Yufang Yuan
- Department of Pediatrics, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University Huaian 223300, China
| | - Weijing Feng
- Department of Pediatrics, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University Huaian 223300, China
| | - Xincui Lu
- Department of Pediatrics, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University Huaian 223300, China
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Ma L, Sun X, Kuai W, Hu J, Yuan Y, Feng W, Lu X. Retracted: Long Noncoding RNA SOX2OT Accelerates the Carcinogenesis of Wilms' Tumor Through ceRNA Through miR-363/FOXP4 Axis. DNA Cell Biol 2018; 37:e1082-e1089. [PMID: 30481065 DOI: 10.1089/dna.2018.4420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
REFERENCES ATCC. www.lgcstandards-atcc.org/Products/All/CRL-1441.aspx?geo_country=it Memorial Sloan Kettering Cancer Cancer. https://www.mskcc.org/research-advantage/support/technology/tangiblematerial/sk-nep-1-human-ewing-sarcoma-cell-line.
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Affiliation(s)
- Li Ma
- Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University , Huaian, China
| | - Xingzhen Sun
- Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University , Huaian, China
| | - Wenxia Kuai
- Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University , Huaian, China
| | - Jian Hu
- Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University , Huaian, China
| | - Yufang Yuan
- Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University , Huaian, China
| | - Weijing Feng
- Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University , Huaian, China
| | - Xincui Lu
- Department of Pediatrics, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University , Huaian, China
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Kaushik V, Yakisich JS, Kumar A, Azad N, Iyer AKV. Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers. Cancers (Basel) 2018; 10:E360. [PMID: 30262730 PMCID: PMC6211070 DOI: 10.3390/cancers10100360] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 09/13/2018] [Accepted: 09/21/2018] [Indexed: 01/08/2023] Open
Abstract
Ion homeostasis is extremely important for the survival of both normal as well as neoplastic cells. The altered ion homeostasis found in cancer cells prompted the investigation of several ionophores as potential anticancer agents. Few ionophores, such as Salinomycin, Nigericin and Obatoclax, have demonstrated potent anticancer activities against cancer stem-like cells that are considered highly resistant to chemotherapy and responsible for tumor relapse. The preclinical success of these compounds in in vitro and in vivo models have not been translated into clinical trials. At present, phase I/II clinical trials demonstrated limited benefit of Obatoclax alone or in combination with other anticancer drugs. However, future development in targeted drug delivery may be useful to improve the efficacy of these compounds. Alternatively, these compounds may be used as leading molecules for the development of less toxic derivatives.
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Affiliation(s)
- Vivek Kaushik
- Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668, USA.
| | - Juan Sebastian Yakisich
- Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668, USA.
| | - Anil Kumar
- Great Plains Health, North Platte, NE 69101, USA.
| | - Neelam Azad
- Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668, USA.
| | - Anand K V Iyer
- Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668, USA.
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