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Yue K, Zhang T, Wang H, Wang B, Mu Y, Li H. MAGI2-AS3 hypermethylated in promoter region promotes migration and invasion of head and neck squamous cell carcinoma via miRNA-31-5p/AR axis. Transl Oncol 2025; 52:102223. [PMID: 39644822 PMCID: PMC11667182 DOI: 10.1016/j.tranon.2024.102223] [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: 03/13/2024] [Revised: 11/18/2024] [Accepted: 11/28/2024] [Indexed: 12/09/2024] Open
Abstract
Molecular regulatory mechanism of MAGI2-AS3 in HNSCC is not yet mature.In this study, we analyzed the methylation level of MAGI2-AS3 promoter and its downstream miR-31-5p/AR axis by bioinformatics methods. qRT-PCR was used to detect the mRNA expression level of each gene, and western blot was used to detect the expression level of AR proteins in tissues and cells. CCK-8, colony formation, wound healing, and cellular invasion assays were used to detect the HNSCC cell proliferation, migration, and invasion. Dual luciferase and RIP assays were performed to validate the binding relationship between genes. The effect of MAGI2-AS3 on HNSCC progression was verified in nude mice in vivo. The low expression of MAGI2-AS3 in HNSCC was caused by hypermethylation of MAGI2-AS3, which could regulate the target of miR-31-5p by sponge adsorption of miR-31-5p, and miR-31-5p could inhibit the expression of AR by directly targeting AR. Thus, MAGI2-AS3 could inhibit the proliferation, migration, and invasion of HNSCC through the miR-31-5p/AR axis. This provided a theoretical basis that MAGI2-AS3 was a potential therapeutic target for HNSCC.
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Affiliation(s)
- Kai Yue
- Department of Oncology, Nanyang Central Hospital, Nanyang 473005, China
| | - Ting Zhang
- Department of Oncology, Nanyang Central Hospital, Nanyang 473005, China
| | - Huanhuan Wang
- Department of Oncology, Nanyang Central Hospital, Nanyang 473005, China
| | - Bo Wang
- Department of Oncology, Nanyang Central Hospital, Nanyang 473005, China
| | - Yalin Mu
- Department of Oncology, Nanyang Central Hospital, Nanyang 473005, China
| | - Hui Li
- Department of Scientific Research, Nanyang Central Hospital, Nanyang 473005, China.
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Jiang Z, Liu T, Wang Y, Li J, Guo L. Effect of lncRNA XIST on acute myeloid leukemia cells via miR-142-5p-PFKP axis. Hematology 2024; 29:2306444. [PMID: 38305210 DOI: 10.1080/16078454.2024.2306444] [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: 02/03/2024] Open
Abstract
Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.
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Affiliation(s)
- Zhaozhi Jiang
- Blood Transfusion Department, Affiliated Hospital of Jilin Medical University, Jilin, China
| | - Tingting Liu
- Pathology Department, Affiliated Hospital of Jilin Medical University, Jilin, China
| | - Youhong Wang
- Blood Transfusion Department, Affiliated Hospital of Jilin Medical University, Jilin, China
| | - Jiao Li
- Blood Transfusion Department, Affiliated Hospital of Jilin Medical University, Jilin, China
| | - Lusheng Guo
- Blood Transfusion Department, Affiliated Hospital of Jilin Medical University, Jilin, China
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Tao H, Weng S, Xu L, Ye J, Fan M, Wang Y, Lin Y, Lin D, Wang Q, Feng S. Target-triggered assembly of plasmon resonance nanostructures for quantitative detection of lncRNA in liver cancer cells via surface enhanced Raman spectroscopy. Biosens Bioelectron 2024; 261:116488. [PMID: 38905860 DOI: 10.1016/j.bios.2024.116488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 05/27/2024] [Accepted: 06/06/2024] [Indexed: 06/23/2024]
Abstract
Long-stranded non-coding RNAs (lncRNA) have important roles in disease as transcriptional regulators, mRNA processing regulators and protein synthesis factors. However, traditional methods for detecting lncRNA are time-consuming and labor-intensive, and the functions of lncRNA are still being explored. Here, we present a surface enhanced Raman spectroscopy (SERS) based biosensor for the detection of lncRNA associated with liver cancer (LC) as well as in situ cellular imaging. Using the dual SERS probes, quantitative detection of lncRNA (DAPK1-215) can be achieved with an ultra-low detection limit of 952 aM by the target-triggered assembly of core-satellite nanostructures. And the reliability of this assay can be further improved with the R2 value of 0.9923 by an internal standard probe that enables the signal dynamic calibration. Meanwhile, the high expression of DAPK1-215 mainly distributed in the cytoplasm was observed in LC cells compared with the normal ones using the SERS imaging method. Moreover, results of cellular function assays showed that DAPK1-215 promoted the migration and invasion of LC by significantly reducing the expression of the structural domain of death associated protein kinase. The development of this biosensor based on SERS can provide a sensitive and specific method for exploring the expression of lncRNA that would be a potential biomarker for the screening of LC.
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Affiliation(s)
- Hong Tao
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, 350117, PR China
| | - Shuyun Weng
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, 350117, PR China
| | - Luyun Xu
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, 350117, PR China
| | - Jianqing Ye
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, 350117, PR China
| | - Min Fan
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, 350117, PR China
| | - Yong Wang
- Institute of Applied Genomics, Fuzhou University, Fuzhou, 350108, PR China
| | - Yao Lin
- The Second Affiliated Hospital of Fujian University of Traditional Chinese Medical University Medicine, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, PR China
| | - Duo Lin
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, 350117, PR China.
| | - Qingshui Wang
- The Second Affiliated Hospital of Fujian University of Traditional Chinese Medical University Medicine, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, PR China.
| | - Shangyuan Feng
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, 350117, PR China.
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Kong YL, Wang HD, Gao M, Rong SZ, Li XX. LncRNA XIST promotes bladder cancer progression by modulating miR-129-5p/TNFSF10 axis. Discov Oncol 2024; 15:65. [PMID: 38446257 PMCID: PMC10917713 DOI: 10.1007/s12672-024-00910-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 02/26/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND The differential expression, biological function, and ceRNA regulatory mechanism of lncRNA XIST in bladder cancer (BC) were investigated, and its clinical values for the early diagnosis of bladder cancer patients were elucidated. METHODS qRT-PCR was employed to detect the expression patterns of lncRNA XIST, miR-129-5p and TNFSF10. The biological functions were measured by CCK8 assay, wound healing assay and transwell assay. Bioinformatics analysis and Dual-Luciferase reporter assay were employed to evaluate the interactions between the lncRNA XIST, miR-129-5p and TNFSF10. RESULTS LncRNA XIST and TNFSF10 were highly expressed and miR-129-5p was low expressed (P < 0.05) in bladder cancer cell line. The depletion of lncRNA XIST inhibited BC proliferation, migration and invasion. Mechanistically, lncRNA XIST could sponge miR-129-5p to regulate TNFSF10 expression in bladder cancer. Furthermore, compared with adjacent tissues, lncRNA XIST and miR-129-5p were lowly expressed (P < 0.01) in bladder cancer tissues, and TNFSF10 was highly expressed (P < 0.001). miR-129-5p and TNFSF10 were associated with the risk of bladder cancer (P < 0.05); the difference in AUC values for the diagnosis of bladder cancer by lncRNA XIST (AUC = 0.739), miR-129-5p (AUC = 0.850) and TNFSF10 (AUC = 0.753) was statistically significant (P < 0.01), and the three genes combined AUC was 0.900, 95%CI was 0.842-0.958 with a sensitivity of 83.3% and specificity of 86.7%. CONCLUSION XIST, an elevated lncRNA in bladder cancer, inhibition of which could suppress the progression of BC. LncRNA XIST and miR-129-5p could form ceRNA to regulate the expression of TNFSF10.
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Affiliation(s)
- Yu-Lin Kong
- Department of Epidemiology, School of Public Health, Mudanjiang Medical University, 3 Tong Xiang Street, Mudanjiang, 157011, Heilongjiang, China
| | - Hui-Dan Wang
- Department of Epidemiology, School of Public Health, Mudanjiang Medical University, 3 Tong Xiang Street, Mudanjiang, 157011, Heilongjiang, China
| | - Meng Gao
- Department of Epidemiology, School of Public Health, Mudanjiang Medical University, 3 Tong Xiang Street, Mudanjiang, 157011, Heilongjiang, China
| | - Sheng-Zhong Rong
- Department of Epidemiology, School of Public Health, Mudanjiang Medical University, 3 Tong Xiang Street, Mudanjiang, 157011, Heilongjiang, China
| | - Xiao-Xia Li
- Department of Epidemiology, School of Public Health, Mudanjiang Medical University, 3 Tong Xiang Street, Mudanjiang, 157011, Heilongjiang, China.
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Chen J, Huang CP, Quan C, Zu X, Ou Z, Tsai YC, Messing E, Yeh S, Chang C. The androgen receptor in bladder cancer. Nat Rev Urol 2023; 20:560-574. [PMID: 37072491 DOI: 10.1038/s41585-023-00761-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2023] [Indexed: 04/20/2023]
Abstract
Bladder cancer is the ninth most common cancer worldwide with a striking sex-based difference in incidence. Emerging evidence indicates that the androgen receptor (AR) might promote the development, progression and recurrence of bladder cancer, contributing to the observed sex differences. Targeting androgen-AR signalling has promise as potential therapy for bladder cancer and helps to suppress progression of this disease. In addition, the identification of a new membrane AR and AR-regulated non-coding RNAs has important implications for bladder cancer treatment. The success of human clinical trials of targeted-AR therapies will help in the development of improved treatments for patients with bladder cancer.
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Affiliation(s)
- Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA
| | - Chi-Ping Huang
- Department of Urology, China Medical University Hospital, Taichung, Taiwan
| | - Chao Quan
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiongbing Zu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
| | - Zhenyu Ou
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA
| | - Yu-Chieh Tsai
- Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA
| | - Edward Messing
- Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA
| | - Shuyuan Yeh
- Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA
| | - Chawnshang Chang
- Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
- Department of Urology, China Medical University Hospital, Taichung, Taiwan.
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Mehmandar-Oskuie A, Jahankhani K, Rostamlou A, Arabi S, Sadat Razavi Z, Mardi A. Molecular landscape of LncRNAs in bladder cancer: From drug resistance to novel LncRNA-based therapeutic strategies. Biomed Pharmacother 2023; 165:115242. [PMID: 37531786 DOI: 10.1016/j.biopha.2023.115242] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/25/2023] [Accepted: 07/25/2023] [Indexed: 08/04/2023] Open
Abstract
Bladder cancer (BC) is a common and serious type of cancer that ranks among the top ten most prevalent malignancies worldwide. Due to the high occurrence rate of BC, the aggressive nature of cancer cells, and their resistance to medication, managing this disease has become a growing challenge in clinical care. Long noncoding RNAs (lncRNAs) are a group of RNA transcripts that do not code for proteins and are more than 200 nucleotides in length. They play a significant role in controlling cellular pathways and molecular interactions during the onset, development and progression of different types of cancers. Recent advancements in high-throughput gene sequencing technology have led to the identification of various differentially expressed lncRNAs in BC, which indicate abnormal expression. In this review, we summarize that these lncRNAs have been found to impact several functions related to the development of BC, including proliferation, cell growth, migration, metastasis, apoptosis, epithelial-mesenchymal transition, and chemo- and radio-resistance. Additionally, lncRNAs may improve prognosis prediction for BC patients, indicating a future use for them as prognostic and diagnostic biomarkers for BC patients. This review highlights that genetic tools and anti-tumor agents, such as CRISPR/Cas systems, siRNA, shRNA, antisense oligonucleotides, and vectors, have been created for use in preclinical cancer models. This has led to a growing interest in using lncRNAs based on positive research findings.
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Affiliation(s)
- Amirreza Mehmandar-Oskuie
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kasra Jahankhani
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arman Rostamlou
- Department of Medical Biology, Faculty of Medicine, University of EGE, IZMIR, Turkey
| | - Sepideh Arabi
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Zahra Sadat Razavi
- Department of Immunology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
| | - Amirhossein Mardi
- Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Science, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.
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Li W, Wang Z, Jiang Z, Yan Y, Yao X, Pan Z, Chen L, Wang F, Wang M, Qin Z. MiR-3960 inhibits bladder cancer progression via targeting of DEXI. Biochem Biophys Res Commun 2023; 668:8-18. [PMID: 37230046 DOI: 10.1016/j.bbrc.2023.05.055] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 05/15/2023] [Indexed: 05/27/2023]
Abstract
PURPOSE MicroRNAs (miRNAs) are dominant cargo in exosomes and act as master regulators of cell function, inhibiting mRNA translation and affecting gene silencing. Some aspects of tissue-specific miRNA transport in bladder cancer (BC) and its role in cancer progression are not fully understood. MATERIALS AND METHODS A microarray was used to identify miRNAs in mouse bladder carcinoma cell line MB49 exosomes. Real-time reverse transcription polymerase chain reaction was used to examine the expression of miRNAs in BC and healthy donor serum. Western blotting and immunohistochemical staining were used to examine the expression of dexamethasone-induced protein (DEXI) in patients with BC. CRISPR-Cas 9 was used to knock out Dexi in MB49, and flow cytometry was performed to test cell proliferation ability and apoptosis under chemotherapy. Human BC organoid culture, miR-3960 transfection, and 293T-exosome-loaded miR-3960 delivery were used to analyze the effect of miR-3960 on BC progression. RESULTS The results showed that miR-3960 levels in BC tissue were positively correlated with patient survival time. Dexi was a major target of miR-3960. Dexi knockout inhibited MB49 cell proliferation and promoted cisplatin- and gemcitabine-induced apoptosis. Transfection of miR-3960 mimic inhibited DEXI expression and organoid growth. In parallel, 293T-exosome-loaded miR-3960 delivery and Dexi knockout significantly inhibited subcutaneous growth of MB49 cells in vivo. CONCLUSION Our results demonstrate the potential role of miR-3960-mediated inhibition of DEXI as a therapeutic strategy against BC.
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Affiliation(s)
- Wenqing Li
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Zihao Wang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Ziming Jiang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Yan Yan
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Xiaohan Yao
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Zhenzhen Pan
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Lin Chen
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Fei Wang
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Ming Wang
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Zhihai Qin
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
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Farzaneh M, Nasrolahi A, Ghaedrahmati F, Masoodi T, Najafi S, Sheykhi-Sabzehpoush M, Dari MAG, Radoszkiewicz K, Uddin S, Azizidoost S, Khoshnam SE. Potential roles of lncRNA-XIST/miRNAs/mRNAs in human cancer cells. Clin Transl Oncol 2023; 25:2015-2042. [PMID: 36853400 DOI: 10.1007/s12094-023-03110-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 01/31/2023] [Indexed: 03/01/2023]
Abstract
Long non-coding RNAs (lncRNAs) are non-coding RNAs that contain more than 200 nucleotides but do not code for proteins. In tumorigenesis, lncRNAs can have both oncogenic and tumor-suppressive properties. X inactive-specific transcript (XIST) is a known lncRNA that has been implicated in X chromosome silencing in female cells. Dysregulation of XIST is associated with an increased risk of various cancers. Therefore, XIST can be a beneficial prognostic biomarker for human malignancies. In this review, we attempt to summarize the emerging roles of XIST in human cancers.
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Affiliation(s)
- Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ava Nasrolahi
- Infectious Ophthalmologic Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Farhoodeh Ghaedrahmati
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Tariq Masoodi
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, 26999, Doha, Qatar
| | - Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Mahrokh Abouali Gale Dari
- Department of Obstetrics and Gynecology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Klaudia Radoszkiewicz
- Translational Platform for Regenerative Medicine, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
| | - Shahab Uddin
- Translational Research Institute and Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Shirin Azizidoost
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Seyed Esmaeil Khoshnam
- Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Emerging RNA-Based Therapeutic and Diagnostic Options: Recent Advances and Future Challenges in Genitourinary Cancers. Int J Mol Sci 2023; 24:ijms24054601. [PMID: 36902032 PMCID: PMC10003365 DOI: 10.3390/ijms24054601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 02/15/2023] [Accepted: 02/23/2023] [Indexed: 03/02/2023] Open
Abstract
Renal cell carcinoma, bladder cancer, and prostate cancer are the most widespread genitourinary tumors. Their treatment and diagnosis have significantly evolved over recent years, due to an increasing understanding of oncogenic factors and the molecular mechanisms involved. Using sophisticated genome sequencing technologies, the non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have all been implicated in the occurrence and progression of genitourinary cancers. Interestingly, DNA, protein, and RNA interactions with lncRNAs and other biological macromolecules drive some of these cancer phenotypes. Studies on the molecular mechanisms of lncRNAs have identified new functional markers that could be potentially useful as biomarkers for effective diagnosis and/or as targets for therapeutic intervention. This review focuses on the mechanisms underlying abnormal lncRNA expression in genitourinary tumors and discusses their role in diagnostics, prognosis, and treatment.
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10
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Xie J. Long Noncoding RNA XIST Regulates Myocardial Infarction via miR-486-5p/SIRT1 Axis. Appl Biochem Biotechnol 2023; 195:725-734. [PMID: 36129595 DOI: 10.1007/s12010-022-04165-3] [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] [Accepted: 07/15/2022] [Indexed: 01/25/2023]
Abstract
Myocardial infarction (MI) is severe heart disease leading to the death worldwide. Long noncoding RNAs (lncRNAs) play a vital role in progression of numerous heart diseases. In the present study, we examined the effects of lncRNA XIST and underlying mechanism on hypoxia-induced apoptosis. In vitro model of MI was established by inducing hypoxia in H9c2 cells. CCK-8 assay was used to measure the cell viability in hypoxia-induced H9c2 cells. The rate of cell apoptosis was assessed by using caspase-3 assay. Transfection was carried out to upregulate the expressions of lncRNA XIST, and miR-486-5p. RT-qPCR was used to measure the levels of lncRNA XIST and miR-486-5p. Also, the relation between XIST and miR-486-5p was confirmed by using Luciferase reporter assay. Our findings revealed that hypoxia significantly downregulated the expressions of XIST. Also, the cell viability markedly increased due to the overexpression of XIST in hypoxia-induced H9c2 cells, while overexpression of XIST significantly reduced the cell apoptosis in hypoxia-induced H9c2 cells. On the other hand, opposite effects were observed due to the downregulation of XIST in hypoxia-induced H9c2 cells. Moreover, XIST negatively regulated the expression of miR-4486-5p and upregulation of XIST inhibited hypoxic injury by downregulating miR-486-5p. Furthermore, SIRT1 expression was negatively regulated by miR-486-5p. We concluded that lncRNA XIST might provide protection against injury induced by hypoxia via miR-486-5p/SIRT1 axis.
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Affiliation(s)
- Jiayong Xie
- Department of of Nephrology, Xinghua People's Hospital, Xinghua, 225700, Jiangsu, China.
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11
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lncRNA-mediated ceRNA network in bladder cancer. Noncoding RNA Res 2022; 8:135-145. [PMID: 36605618 PMCID: PMC9792360 DOI: 10.1016/j.ncrna.2022.12.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 12/10/2022] [Accepted: 12/13/2022] [Indexed: 12/15/2022] Open
Abstract
Bladder cancer is a common disease associated with high rates of morbidity and mortality. Although immunotherapy approaches such as adoptive T-cell therapy and immune checkpoint blockade have been investigated for the treatment of bladder cancer, their off-target effects and ability to affect only single targets have led to clinical outcomes that are far from satisfactory. Therefore, it is important to identify novel targets that can effectively control tumor growth and metastasis. It is well known that long noncoding RNAs (lncRNAs) are powerful regulators of gene expression. Increasing evidence has shown that dysregulated lncRNAs in bladder cancer are involved in cancer cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). In this review, we focus on the roles and underlying mechanisms of lncRNA-mediated competing endogenous RNA (ceRNA) networks in the regulation of bladder cancer progression. In addition, we discuss the potential of targeting lncRNA-mediated ceRNA networks to overcome cancer treatment resistance and its association with clinicopathological features and outcomes in bladder cancer patients. We hope this review will stimulate research to develop more effective therapeutic approaches for bladder cancer treatment.
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Braga EA, Fridman MV, Burdennyy AM, Filippova EA, Loginov VI, Pronina IV, Dmitriev AA, Kushlinskii NE. Regulation of the Key Epithelial Cancer Suppressor miR-124 Function by Competing Endogenous RNAs. Int J Mol Sci 2022; 23:13620. [PMID: 36362406 PMCID: PMC9655303 DOI: 10.3390/ijms232113620] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 12/01/2023] Open
Abstract
A decrease in the miR-124 expression was observed in various epithelial cancers. Like a classical suppressor, miR-124 can inhibit the translation of multiple oncogenic proteins. Epigenetic mechanisms play a significant role in the regulation of miR-124 expression and involve hypermethylation of the MIR-124-1/-2/-3 genes and the effects of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) according to the model of competing endogenous RNAs (ceRNAs). More than 40 interactomes (lncRNA/miR-124/mRNA) based on competition between lncRNAs and mRNAs for miR-124 binding have been identified in various epithelial cancers. LncRNAs MALAT1, NEAT1, HOXA11-AS, and XIST are the most represented in these axes. Fourteen axes (e.g., SND1-IT1/miR-124/COL4A1) are involved in EMT and/or metastasis. Moreover, eight axes (e.g., OIP5-AS1/miR-124-5p/IDH2) are involved in key pathways, such as Wnt/b-catenin, E2F1, TGF-β, SMAD, ERK/MAPK, HIF-1α, Notch, PI3K/Akt signaling, and cancer cell stemness. Additionally, 15 axes impaired patient survival and three axes reduced chemo- or radiosensitivity. To date, 14 cases of miR-124 regulation by circRNAs have been identified. Half of them involve circHIPK3, which belongs to the exonic ecircRNAs and stimulates cell proliferation, EMT, autophagy, angiogenesis, and multidrug resistance. Thus, miR-124 and its interacting partners may be considered promising targets for cancer therapy.
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Affiliation(s)
- Eleonora A. Braga
- Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
- Research Centre for Medical Genetics, 115522 Moscow, Russia
| | - Marina V. Fridman
- Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia
| | | | - Elena A. Filippova
- Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
| | - Vitaly I. Loginov
- Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
- Research Centre for Medical Genetics, 115522 Moscow, Russia
| | - Irina V. Pronina
- Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
| | - Alexey A. Dmitriev
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
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13
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Tan W, Yuan Y, Huang H, Ma J, Li Y, Gou Y, Wu H, Hu Z. Comprehensive analysis of autophagy related long non-coding RNAs in prognosis, immunity, and treatment of muscular invasive bladder cancer. Sci Rep 2022; 12:11242. [PMID: 35787635 PMCID: PMC9253343 DOI: 10.1038/s41598-022-13952-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 05/31/2022] [Indexed: 02/08/2023] Open
Abstract
To predict disease outcome in muscle-invasive bladder cancer (MIBC), we constructed a prognostic autophagy-related (PAR) lncRNA signature. Comprehensive bioinformatics analyses were performed using data from TCGA and GTEx databases. Univariate Cox, and least absolute shrinkage and selection operator regression analyses were also performed, based on differentially expressed genes, to identify PAR-related lncRNAs to establish the signature. Furthermore, the Kaplan–Meier OS curve and receiver operating characteristic curve analyses were performed and a nomogram was constructed, all of which together confirmed the strong predictive ability of the constructed signature. Patients with MIBC were then divided into high- and low-risk groups. Gene enrichment and immune infiltration analyses revealed the potential mechanisms in MIBC. We also further evaluated the signature of molecules related to immune checkpoints and the sensitivity toward chemotherapeutic agents and antitumor-targeted drugs to find better treatment prescriptions. We identified a number of PAR-related lncRNA signatures, including HCP5, AC024060.1, NEAT1, AC105942.1, XIST, MAFG-DT, and NR2F1-AS1, which could be valuable prognostic tools to develop more efficient, individualized drug therapies for MIBC patients.
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Affiliation(s)
- Wei Tan
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ye Yuan
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hao Huang
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junhao Ma
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yadong Li
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yuanqing Gou
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hao Wu
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Zili Hu
- Department of Urology Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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14
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Construction and Analysis of lncRNA-Associated ceRNA Network in Atherosclerotic Plaque Formation. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4895611. [PMID: 35463977 PMCID: PMC9033352 DOI: 10.1155/2022/4895611] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/05/2022] [Accepted: 03/24/2022] [Indexed: 11/17/2022]
Abstract
Atherosclerosis (AS) is a vascular disease with plaque formation. Unstable plaques can be expected to result in cardiovascular disease, such as myocardial infarction and stroke. Studies have verified that long noncoding RNAs (lncRNAs) play a critical role in atherosclerotic plaque formation (APF), including MALAT1, GAS5, and H19. A ceRNA network is a combination of these two interacting processes, which regulate the occurrence and progression of many diseases. However, lncRNA-associated ceRNA network in terms of APF is limited. This study sought to discover novel potential biomarkers and ceRNA network for APF. We designed a triple network based on the lncRNA-miRNA and mRNA-miRNA pairs obtained from lncRNASNP and starBase. Differentially expressed genes (DEGs) and lncRNAs in human vascular tissues derived from the Gene Expression Omnibus database (GSE43292, GSE97210) were systematically selected and analyzed. A ceRNA network was constructed by hypergeometric test, including 8 lncRNAs, 243 miRNAs, and 8 mRNAs. APF-related ceRNA structure was discovered for the first time by combining network analysis and statistical validation. Topological analysis determined the key lncRNAs with the highest centroid. GO and KEGG enrichment analysis indicated that the ceRNA network was primarily enriched in “regulation of platelet-derived growth factor receptor signaling pathway,” “negative regulation of leukocyte chemotaxis,” and “axonal fasciculation.” A functional lncRNA, HAND2-AS1, was identified in the ceRNA network, and the main miRNA (miRNA-570-3p) regulated by HAND2-AS1 was further screened. This present study elucidated the important function of lncRNA in the origination and progression of APF and indicated the potential use of these hub nodes as diagnostic biomarkers and therapeutic targets.
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15
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Fang C, Huang X, Dai J, He W, Xu L, Sun F. The circular RNA circFARSA sponges microRNA-330-5p in tumor cells with bladder cancer phenotype. BMC Cancer 2022; 22:373. [PMID: 35395756 PMCID: PMC8991568 DOI: 10.1186/s12885-022-09467-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 03/28/2022] [Indexed: 11/17/2022] Open
Abstract
Background Circular RNAs (circRNAs) modulate gene expression in various malignancies. However, their roles in the occurrence of bladder cancer (BC) and their underlying mechanisms of action are currently unclear. Methods We measured levels of the circRNA phenylalanyl-tRNA synthetase subunit alpha (circFARSA) and target microRNAs (miRNAs/miRs) in BC tissues and cell lines using quantitative polymerase chain reactions. The functions of circFARSA in tumor formation were examined in mice with BC xenografts in vivo and in BC cells via determination of their proliferation, activity, apoptosis, metastasis, and invasion in vitro using cell counting kit-8 assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry, western blotting, Transwell assays, and cell wound healing assays. Interactions between miR-330 and circFARSA were predicted and confirmed by bioinformatic processing and dual-luciferase reporter gene assays, respectively. Expression profiles of miR-330 targets in BC cells were assessed via western blotting. Results circFARSA expression was markedly upregulated in BC tissues and cell lines compared with that in normal bladder samples. Silencing circFARSA expression decreased BC cell proliferation, invasion, and migration but induced their apoptosis in vitro. Downregulating circFARSA expression slowed tumor growth in vivo and directly sponged miR-330 and inhibited its function in BC cells in vitro. Inhibiting miR-330 expression abolished the regulatory effects of circFARSA silencing on the tumor phenotypes of BC cells. Conclusions circFARSA expression is upregulated and exerts oncogenic functions in BC by sponging miR-330. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09467-7.
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Affiliation(s)
- Chen Fang
- Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijing 2nd Road, Shanghai, 200025, China
| | - Xin Huang
- Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijing 2nd Road, Shanghai, 200025, China
| | - Jun Dai
- Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijing 2nd Road, Shanghai, 200025, China
| | - Wei He
- Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijing 2nd Road, Shanghai, 200025, China
| | - Le Xu
- Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijing 2nd Road, Shanghai, 200025, China
| | - Fukang Sun
- Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijing 2nd Road, Shanghai, 200025, China.
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16
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Li J, Ming Z, Yang L, Wang T, Liu G, Ma Q. Long noncoding RNA XIST: Mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities. Genes Dis 2022; 9:1478-1492. [PMID: 36157489 PMCID: PMC9485286 DOI: 10.1016/j.gendis.2022.04.007] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/16/2022] [Accepted: 04/18/2022] [Indexed: 11/30/2022] Open
Abstract
Sexual dimorphism has been reported in various human diseases including autoimmune diseases, neurological diseases, pulmonary arterial hypertension, and some types of cancers, although the underlying mechanisms remain poorly understood. The long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in X chromosome inactivation (XCI) in female placental mammals, a process that ensures the balanced expression dosage of X-linked genes between sexes. XIST is abnormally expressed in many sex-biased diseases. In addition, escape from XIST-mediated XCI and skewed XCI also contribute to sex-biased diseases. Therefore, its expression or modification can be regarded as a biomarker for the diagnosis and prognosis of many sex-biased diseases. Genetic manipulation of XIST expression can inhibit the progression of some of these diseases in animal models, and therefore XIST has been proposed as a potential therapeutic target. In this manuscript, we summarize the current knowledge about the mechanisms for XIST-mediated XCI and the roles of XIST in sex-biased diseases, and discuss potential therapeutic strategies targeting XIST.
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17
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The Role of Androgen Receptor and microRNA Interactions in Androgen-Dependent Diseases. Int J Mol Sci 2022; 23:ijms23031553. [PMID: 35163477 PMCID: PMC8835816 DOI: 10.3390/ijms23031553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 01/25/2022] [Accepted: 01/25/2022] [Indexed: 12/31/2022] Open
Abstract
The androgen receptor (AR) is a member of the steroid hormone receptor family of nuclear transcription factors. It is present in the primary/secondary sexual organs, kidneys, skeletal muscles, adrenal glands, skin, nervous system, and breast. Abnormal AR functioning has been identified in numerous diseases, specifically in prostate cancer (PCa). Interestingly, recent studies have indicated a relationship between the AR and microRNA (miRNA) crosstalk and cancer progression. MiRNAs are small, endogenous, non-coding molecules that are involved in crucial cellular processes, such as proliferation, apoptosis, or differentiation. On the one hand, AR may be responsible for the downregulation or upregulation of specific miRNA, while on the other hand, AR is often a target of miRNAs due to their regulatory function on AR gene expression. A deeper understanding of the AR–miRNA interactions may contribute to the development of better diagnostic tools as well as to providing new therapeutic approaches. While most studies usually focus on the role of miRNAs and AR in PCa, in this review, we go beyond PCa and provide insight into the most recent discoveries about the interplay between AR and miRNAs, as well as about other AR-associated and AR-independent diseases.
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18
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Yang J, Qi M, Fei X, Wang X, Wang K. Long non-coding RNA XIST: a novel oncogene in multiple cancers. Mol Med 2021; 27:159. [PMID: 34930117 PMCID: PMC8686246 DOI: 10.1186/s10020-021-00421-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 12/06/2021] [Indexed: 01/01/2023] Open
Abstract
Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is an important lncRNA derived from the XIST gene in mammals. XIST is abnormally expressed in numerous tumors, in most of which XIST functions as an oncogene. XIST is involved in multiple aspects of carcinogenesis, including tumor onset, progression, and prognosis. In our review, we collected and analyzed the recent studies on the impact of XIST in human tumor development. The multilevel molecular functions of XIST in human tumors are comprehensively reviewed to clarify the pathologic mechanisms and to offer a novel direction for further study.
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Affiliation(s)
- Jun Yang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Manlong Qi
- Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Xiang Fei
- Department of Urology, Shengjing Hospital of China Medical University, #36 Sanhao Street, Heping, Liaoning, 110004, Shenyang, China
| | - Xia Wang
- Department of Urology, Shengjing Hospital of China Medical University, #36 Sanhao Street, Heping, Liaoning, 110004, Shenyang, China
| | - Kefeng Wang
- Department of Urology, Shengjing Hospital of China Medical University, #36 Sanhao Street, Heping, Liaoning, 110004, Shenyang, China.
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19
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Zhao LX, Zhang K, Shen BB, Li JN. Mesenchymal stem cell-derived exosomes for gastrointestinal cancer. World J Gastrointest Oncol 2021; 13:1981-1996. [PMID: 35070036 PMCID: PMC8713327 DOI: 10.4251/wjgo.v13.i12.1981] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/15/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) malignancies, a series of malignant conditions originating from the digestive system, include gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. GI cancers have been regarded as the leading cancer-related cause of death in recent years. Therefore, it is essential to develop effective treatment strategies for GI malignancies. Mesenchymal stem cells (MSCs), a type of distinct non-hematopoietic stem cells and an important component of the tumor microenvironment, play important roles in regulating GI cancer development and progression through multiple mechanisms, such as secreting cytokines and direct interactions. Currently, studies are focusing on the anti-cancer effect of MSCs on GI malignancies. However, the effects and functional mechanisms of MSC-derived exosomes on GI cancer are less studied. MSC-derived exosomes can regulate GI tumor growth, drug response, metastasis, and invasion through transplanting proteins and miRNA to tumor cells to activate the specific signal pathway. Besides, the MSC-derived exosomes are also seen as an important drug delivery system and have shown potential in anti-cancer treatment. This study aims to summarize the effect and biological functions of MSC-derived exosomes on the development of GI cancers and discuss their possible clinical applications for the treatment of GI malignancies.
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Affiliation(s)
- Lin-Xian Zhao
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Bing-Bing Shen
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Jian-Nan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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20
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Taheri M, Khoshbakht T, Jamali E, Kallenbach J, Ghafouri-Fard S, Baniahmad A. Interaction between Non-Coding RNAs and Androgen Receptor with an Especial Focus on Prostate Cancer. Cells 2021; 10:3198. [PMID: 34831421 PMCID: PMC8619311 DOI: 10.3390/cells10113198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/10/2021] [Accepted: 11/11/2021] [Indexed: 12/16/2022] Open
Abstract
The androgen receptor (AR) is a member of the nuclear receptor superfamily and has three functional domains, namely the N-terminal, DNA binding, and C-terminal domain. The N-terminal domain harbors potent transactivation functions, whereas the C-terminal domain binds to androgens and antiandrogens used to treat prostate cancer. AR has genomic activity being DNA binding-dependent or through interaction with other DNA-bound transcription factors, as well as a number of non-genomic, non-canonical functions, such as the activation of the ERK, AKT, and MAPK pathways. A bulk of evidence indicates that non-coding RNAs have functional interactions with AR. This type of interaction is implicated in the pathogenesis of human malignancies, particularly prostate cancer. In the current review, we summarize the available data on the role of microRNAs, long non-coding RNAs, and circular RNAs on the expression of AR and modulation of AR signaling, as well as the effects of AR on their expression. Recognition of the complicated interaction between non-coding RNAs and AR has practical importance in the design of novel treatment options, as well as modulation of response to conventional therapeutics.
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Affiliation(s)
- Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1983535511, Iran;
- Institute of Human Genetics, Jena University Hospital, 07747 Jena, Germany;
| | - Tayyebeh Khoshbakht
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1983535511, Iran;
| | - Elena Jamali
- Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1983535511, Iran;
| | - Julia Kallenbach
- Institute of Human Genetics, Jena University Hospital, 07747 Jena, Germany;
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983535511, Iran
| | - Aria Baniahmad
- Institute of Human Genetics, Jena University Hospital, 07747 Jena, Germany;
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21
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Asadi MR, Hassani M, Kiani S, Sabaie H, Moslehian MS, Kazemi M, Ghafouri-Fard S, Taheri M, Rezazadeh M. The Perspective of Dysregulated LncRNAs in Alzheimer's Disease: A Systematic Scoping Review. Front Aging Neurosci 2021; 13:709568. [PMID: 34621163 PMCID: PMC8490871 DOI: 10.3389/fnagi.2021.709568] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/12/2021] [Indexed: 12/22/2022] Open
Abstract
LncRNAs act as part of non-coding RNAs at high levels of complex and stimulatory configurations in basic molecular mechanisms. Their extensive regulatory activity in the CNS continues on a small scale, from the functions of synapses to large-scale neurodevelopment and cognitive functions, aging, and can be seen in both health and disease situations. One of the vast consequences of the pathological role of dysregulated lncRNAs in the CNS due to their role in a network of regulatory pathways can be manifested in Alzheimer's as a neurodegenerative disease. The disease is characterized by two main hallmarks: amyloid plaques due to the accumulation of β-amyloid components and neurofibrillary tangles (NFT) resulting from the accumulation of phosphorylated tau. Numerous studies in humans, animal models, and various cell lines have revealed the role of lncRNAs in the pathogenesis of Alzheimer's disease. This scoping review was performed with a six-step strategy and based on the Prisma guideline by systematically searching the publications of seven databases. Out of 1,591 records, 69 articles were utterly aligned with the specified inclusion criteria and were summarized in the relevant table. Most of the studies were devoted to BACE1-AS, NEAT1, MALAT1, and SNHG1 lncRNAs, respectively, and about one-third of the studies investigated a unique lncRNA. About 56% of the studies reported up-regulation, and 7% reported down-regulation of lncRNAs expressions. Overall, this study was conducted to investigate the association between lncRNAs and Alzheimer's disease to make a reputable source for further studies and find more molecular therapeutic goals for this disease.
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Affiliation(s)
- Mohammad Reza Asadi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Hassani
- Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Shiva Kiani
- Department of Molecular Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hani Sabaie
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Marziyeh Sadat Moslehian
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Kazemi
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Rezazadeh
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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22
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Mirzaei S, Paskeh MDA, Hashemi F, Zabolian A, Hashemi M, Entezari M, Tabari T, Ashrafizadeh M, Raee P, Aghamiri S, Aref AR, Leong HC, Kumar AP, Samarghandian S, Zarrabi A, Hushmandi K. Long non-coding RNAs as new players in bladder cancer: Lessons from pre-clinical and clinical studies. Life Sci 2021; 288:119948. [PMID: 34520771 DOI: 10.1016/j.lfs.2021.119948] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/02/2021] [Accepted: 09/06/2021] [Indexed: 12/15/2022]
Abstract
The clinical management of bladder cancer (BC) has become an increasing challenge due to high incidence rate of BC, malignant behavior of cancer cells and drug resistance. The non-coding RNAs are considered as key factors involved in BC progression. The long non-coding RNAs (lncRNAs) are RNA molecules and do not encode proteins. They have more than 200 nucleotides in length and affect gene expression at epigenetic, transcriptional and post-transcriptional phases. The lncRNAs demonstrate abnormal expression in BC cells and tissues. The present aims to identifying lncRNAs with tumor-suppressor and tumor-promoting roles, and evaluating their roles as regulatory of growth and migration. Apoptosis, glycolysis and EMT are tightly regulated by lncRNAs in BC. Response of BC cells to cisplatin, doxorubicin and gemcitabine chemotherapy is modulated by lncRNAs. LncRNAs regulate immune cell infiltration in tumor microenvironment and affect response of BC cells to immunotherapy. Besides, lncRNAs are able to regulate microRNAs, STAT3, Wnt, PTEN and PI3K/Akt pathways in affecting both proliferation and migration of BC cells. Noteworthy, anti-tumor compounds and genetic tools such as siRNA, shRNA and CRISPR/Cas systems can regulate lncRNA expression in BC. Finally, lncRNAs and exosomal lncRNAs can be considered as potential diagnostic and prognostic tools in BC.
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Affiliation(s)
- Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mahshid Deldar Abad Paskeh
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Farid Hashemi
- Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Amirhossein Zabolian
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mehrdad Hashemi
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Teimour Tabari
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Milad Ashrafizadeh
- Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey; Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956 Istanbul, Turkey.
| | - Pourya Raee
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahin Aghamiri
- Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Reza Aref
- Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Xsphera Biosciences Inc., 6 Tide Street, Boston, MA 02210, USA
| | - Hin Chong Leong
- Cancer Science Institute of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Alan Prem Kumar
- Cancer Science Institute of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
| | - Saeed Samarghandian
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956 Istanbul, Turkey.
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
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Guo W, Gai Q, Ma Y, Shan Z, Wu J. LINC01410 leads the migration, invasion and EMT of bladder cancer cells by modulating miR-4319 / Snail1. Cancer Cell Int 2021; 21:429. [PMID: 34391433 PMCID: PMC8364693 DOI: 10.1186/s12935-021-02119-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 07/28/2021] [Indexed: 12/02/2022] Open
Abstract
Background Several previous studies have implied the significance of lncRNA1410 (LINC01410) in gastric cancer, rectal cancer, and cervical cancer. Nevertheless, the potential of LINC01410 in bladder cancer (BC) development has not been addressed. Methods The related mechanisms were explored by qRT-PCR analysis, CCK-8 assay, cell transfection assay, Transwell assay, Western Blot analysis, Luciferase reporter assay and RNA pull-down assay. Results In the following study, LINC01410, characterized as an oncogene, exhibited high levels of expression in BC tissues as compared to normal tissues and its expression leads to a reduced prognosis of BC. Functional characterization of LINC01410 showed that knocking down LINC01410 could markedly reduce the invasion and proliferation capacity of T24 and 5637 cells. Mechanistically, LINC01410 served as a sponge for miR-4319 and the findings were further attested through luciferase reporter assay. Analysis of miR-4319 demonstrated its low expression in BC tissues as compared to normal tissues and knocking down LINC01410 significantly increased miR-4319. Data obtained from rescue assay discovered that silencing of miR-4319 in T24 and 5637 cells restored the proliferation and invasion capacity of LINC01410. Conclusions Taken together, this study is the first report on the oncogenic potential of LINC01410 in BC development by upregulating Snail1 protein and downregulating miR-4319. Trial registration Retrospectively registered. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02119-z.
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Affiliation(s)
- Wei Guo
- Department of Radiotherapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, People's Republic of China
| | - Qimei Gai
- Department of Vascular Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, People's Republic of China
| | - Yue Ma
- Department of Urology, Mianyang Central Hospital, Mianyang, 621000, Sichuan, People's Republic of China
| | - Zhengfei Shan
- Department of Organ Transplantation, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, People's Republic of China. .,Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, People's Republic of China.
| | - Jitao Wu
- Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, People's Republic of China.
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Ghafouri-Fard S, Dashti S, Farsi M, Taheri M, Mousavinejad SA. X-Inactive-Specific Transcript: Review of Its Functions in the Carcinogenesis. Front Cell Dev Biol 2021; 9:690522. [PMID: 34179019 PMCID: PMC8226258 DOI: 10.3389/fcell.2021.690522] [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: 04/03/2021] [Accepted: 05/13/2021] [Indexed: 01/03/2023] Open
Abstract
X-inactive-specific transcript (XIST) is one of the firstly discovered long non-coding RNAs with prominent roles in the process of X inactivation. Moreover, this transcript contributes in the carcinogenic process in different tissues. In addition to interacting with chromatin modifying molecules, XIST can be served as a molecular sponge for miRNAs to modulate expression of miRNA targets. Most of the studies have indicated an oncogenic role for XIST. However, in prostate cancer, a single study has indicated a tumor suppressor role for this lncRNA. Similar result has been reported for XIST in oral squamous cell carcinoma. In hepatocellular carcinoma, breast cancer, ovarian cancer, osteosarcoma, and renal cell carcinoma, different studies have reported inconsistent results. In the present manuscript, we review function of XIST in the carcinogenesis.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Dashti
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Molood Farsi
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Ali Mousavinejad
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wang W, Min L, Qiu X, Wu X, Liu C, Ma J, Zhang D, Zhu L. Biological Function of Long Non-coding RNA (LncRNA) Xist. Front Cell Dev Biol 2021; 9:645647. [PMID: 34178980 PMCID: PMC8222981 DOI: 10.3389/fcell.2021.645647] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 05/12/2021] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA X-inactive specific transcript (lncRNA Xist) serves as an important regulator of cell growth and development. Despites its original roles in X-chromosome dosage compensation, lncRNA Xist also participates in the development of tumor and other human diseases by functioning as a competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress in understanding the cellular functions of lncRNA Xist in mammalian cells and discussed current knowledge regarding the ceRNA network of lncRNA Xist in various diseases. Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nt in length and without an apparent protein-coding capacity (Furlan and Rougeulle, 2016; Maduro et al., 2016). These RNAs are believed to be transcribed by the approximately 98-99% non-coding regions of the human genome (Derrien et al., 2012; Fu, 2014; Montalbano et al., 2017; Slack and Chinnaiyan, 2019), as well as a large variety of genomic regions, such as exonic, tronic, and intergenic regions. Hence, lncRNAs are also divided into eight categories: Intergenic lncRNAs, Intronic lncRNAs, Enhancer lncRNAs, Promoter lncRNAs, Natural antisense/sense lncRNAs, Small nucleolar RNA-ended lncRNAs (sno-lncRNAs), Bidirectional lncRNAs, and non-poly(A) lncRNAs (Ma et al., 2013; Devaux et al., 2015; St Laurent et al., 2015; Chen, 2016; Quinn and Chang, 2016; Richard and Eichhorn, 2018; Connerty et al., 2020). A range of evidence has suggested that lncRNAs function as key regulators in crucial cellular functions, including proliferation, differentiation, apoptosis, migration, and invasion, by regulating the expression level of target genes via epigenomic, transcriptional, or post-transcriptional approaches (Cao et al., 2018). Moreover, lncRNAs detected in body fluids were also believed to serve as potential biomarkers for the diagnosis, prognosis, and monitoring of disease progression, and act as novel and potential drug targets for therapeutic exploitation in human disease (Jiang W. et al., 2018; Zhou et al., 2019a). Long non-coding RNA X-inactive specific transcript (lncRNA Xist) are a set of 15,000-20,000 nt sequences localized in the X chromosome inactivation center (XIC) of chromosome Xq13.2 (Brown et al., 1992; Debrand et al., 1998; Kay, 1998; Lee et al., 2013; da Rocha and Heard, 2017; Yang Z. et al., 2018; Brockdorff, 2019). Previous studies have indicated that lncRNA Xist regulate X chromosome inactivation (XCI), resulting in the inheritable silencing of one of the X-chromosomes during female cell development. Also, it serves a vital regulatory function in the whole spectrum of human disease (notably cancer) and can be used as a novel diagnostic and prognostic biomarker and as a potential therapeutic target for human disease in the clinic (Liu et al., 2018b; Deng et al., 2019; Dinescu et al., 2019; Mutzel and Schulz, 2020; Patrat et al., 2020; Wang et al., 2020a). In particular, lncRNA Xist have been demonstrated to be involved in the development of multiple types of tumors including brain tumor, Leukemia, lung cancer, breast cancer, and liver cancer, with the prominent examples outlined in Table 1. It was also believed that lncRNA Xist (Chaligne and Heard, 2014; Yang Z. et al., 2018) contributed to other diseases, such as pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, and osteoarthritis chondrocytes, and more specific details can be found in Table 2. This review summarizes the current knowledge on the regulatory mechanisms of lncRNA Xist on both chromosome dosage compensation and pathogenesis (especially cancer) processes, with a focus on the regulatory network of lncRNA Xist in human disease.
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Affiliation(s)
| | | | | | | | | | | | - Dongyi Zhang
- Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, China
| | - Lingyun Zhu
- Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, China
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Swaminathan G, Shigna A, Kumar A, Byroju VV, Durgempudi VR, Dinesh Kumar L. RNA Interference and Nanotechnology: A Promising Alliance for Next Generation Cancer Therapeutics. FRONTIERS IN NANOTECHNOLOGY 2021. [DOI: 10.3389/fnano.2021.694838] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Cancer is a significant health hazard of the 21st century, and GLOBOCAN predicts increasing cancer incidence in the coming decades. Though several conventional treatment modalities exist, most of them end up causing off-target and debilitating effects, and drug resistance acquisition. Advances in our understanding of tumor molecular biology offer alternative strategies for precise, robust, and potentially less toxic treatment paradigms for circumventing the disease at the cellular and molecular level. Several deregulated molecules associated with tumorigenesis have been developed as targets in RNA interference (RNAi) based cancer therapeutics. RNAi, a post-transcriptional gene regulation mechanism, has significantly gained attention because of its precise multi-targeted gene silencing. Although the RNAi approach is favorable, the direct administration of small oligonucleotides has not been fruitful because of their inherent lower half-lives and instability in the biological systems. Moreover, the lack of an appropriate delivery system to the primary site of the tumor that helps determine the potency of the drug and its reach, has limited the effective medical utilization of these bio-drugs. Nanotechnology, with its unique characteristics of enhanced permeation and better tumor-targeting efficiency, offers promising solutions owing to the various possibilities and amenability for modifications of the nanoparticles to augment cancer therapeutics. Nanoparticles could be made multimodal, by designing and synthesizing multiple desired functionalities, often resulting in unique and potentially applicable biological structures. A small number of Phase I clinical trials with systemically administered siRNA molecules conjugated with nanoparticles have been completed and the results are promising, indicating that, these new combinatorial therapies can successfully and safely be used to inhibit target genes in cancer patients to alleviate some of the disease burden. In this review, we highlight different types of nano-based delivery strategies for engineering Nano-RNAi-based bio drugs. Furthermore, we have highlighted the insights gained from current research that are entering the preclinical evaluation and information about initial clinical developments, shaping the future for next generation cancer therapeutics.
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Guo C, Li X, Xie J, Liu D, Geng J, Ye L, Yan Y, Yao X, Luo M. Long Noncoding RNA SNHG1 Activates Autophagy and Promotes Cell Invasion in Bladder Cancer. Front Oncol 2021; 11:660551. [PMID: 34055628 PMCID: PMC8158816 DOI: 10.3389/fonc.2021.660551] [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: 01/29/2021] [Accepted: 04/26/2021] [Indexed: 12/19/2022] Open
Abstract
LncRNAs play important roles in bladder cancer. However, only a few studies report on the correlation between lncRNAs expression and autophagy in bladder cancer. This study aimed to explore the effect of lncRNA on autophagy in bladder cancer. The findings showed high expression of SNHG1 in the bladder cancer cells and tumor tissues. The high expression of SNHG1 was positively correlated with bladder cancer cell invasion, proliferation, and autophagy. This finding implies that SNHG1 promotes bladder cancer cell invasion and proliferation via autophagy. Further analysis of the mechanism of action of SNHG1 showed that it functions as a sponge of miRNA-493 in bladder cancer. miRNA-493 binds on the 3’ -UTR of ATG14 mRNA thus affecting ATG14 protein expression, which is implicated in autophagy. These findings are supported by previous preclinical studies using multiple Bca cell lines and TCGA, which demonstrate that SNHG1 plays an oncogenic role by acting as a sponge of miR-493-5p or as its ceRNA. Upregulation of SNHG1 promotes proliferation, invasion, and autophagy of bladder cancer cells through the miR-493-5p/ATG14/autophagy pathway. Therefore, SNHG1 may act as a potential therapeutic target for the treatment of bladder cancer.
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Affiliation(s)
- Changcheng Guo
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xin Li
- Department of Urology, Taizhou Center Hospital, Taizhou University, Zhejiang, China
| | - Jinbo Xie
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Dan Liu
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jiang Geng
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Lin Ye
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yang Yan
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xudong Yao
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ming Luo
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
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Xiong Y, Zu X, Wang L, Li Y, Chen M, He W, Qi L. The VIM-AS1/miR-655/ZEB1 axis modulates bladder cancer cell metastasis by regulating epithelial-mesenchymal transition. Cancer Cell Int 2021; 21:233. [PMID: 33902589 PMCID: PMC8074428 DOI: 10.1186/s12935-021-01841-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 02/17/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Invasive bladder tumors cause a worse prognosis in patients and remain a clinical challenge. Epithelial-mesenchymal transition (EMT) is associated with bladder cancer metastasis. In the present research, we attempted to demonstrate a novel mechanism by which a long noncoding RNA (lncRNA)-miRNA-mRNA axis regulates EMT and metastasis in bladder cancer. METHODS Immunofluorescence (IF) staining was used to detect Vimentin expression. The protein expression of ZEB1, Vimentin, E-cadherin, and Snail was investigated by using immunoblotting assays. Transwell assays were performed to detect the invasive capacity of bladder cancer cells. A wound healing assay was used to measure the migratory capacity of bladder cancer cells. RESULTS Herein, we identified lncRNA VIM-AS1 as a highly- expressed lncRNA in bladder cancer, especially in metastatic bladder cancer tissues and high-metastatic bladder cancer cell lines. By acting as a ceRNA for miR-655, VIM-AS1 competed with ZEB1 for miR-655 binding, therefore eliminating the miR-655-mediated suppression of ZEB1, finally promoting EMT in both high- and low-metastatic bladder cancer cells and enhancing cancer cell metastasis. CONCLUSIONS In conclusion, the VIM-AS1/miR-655/ZEB1 axis might be a promising target for improving bladder cancer metastasis via an EMT-related mechanism.
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Affiliation(s)
- Yaoyao Xiong
- Department of Cardiopulmonary Bypass, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Xiongbing Zu
- Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China
| | - Long Wang
- Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China
| | - Yuan Li
- Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China
| | - Minfeng Chen
- Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China
| | - Wei He
- Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China.
| | - Lin Qi
- Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China
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The Role of Androgens and Androgen Receptor in Human Bladder Cancer. Biomolecules 2021; 11:biom11040594. [PMID: 33919565 PMCID: PMC8072960 DOI: 10.3390/biom11040594] [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: 03/01/2021] [Revised: 04/12/2021] [Accepted: 04/15/2021] [Indexed: 12/15/2022] Open
Abstract
Bladder cancer (urothelial carcinoma) is one of the most frequently diagnosed neoplasms, with an estimated half a million new cases and 200,000 deaths per year worldwide. This pathology mainly affects men. Men have a higher risk (4:1) of developing bladder cancer than women. Cigarette smoking and exposure to chemicals such as aromatic amines, and aniline dyes have been established as risk factors for bladder cancer and may contribute to the sex disparity. Male internal genitalia, including the urothelium and prostate, are derived from urothelial sinus endoderm; both tissues express the androgen receptor (AR). Several investigations have shown evidence that the AR plays an important role in the initiation and development of different types of cancer including bladder cancer. In this article, we summarize the available data that help to explain the role of the AR in the development and progression of bladder cancer, as well as the therapies used for its treatment.
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Wang J, Yin G, Bian H, Yang J, Zhou P, Yan K, Liu C, Chen P, Zhu J, Li Z, Xue T. LncRNA XIST upregulates TRIM25 via negatively regulating miR-192 in hepatitis B virus-related hepatocellular carcinoma. Mol Med 2021; 27:41. [PMID: 33858324 PMCID: PMC8050905 DOI: 10.1186/s10020-021-00278-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 02/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Long non-coding RNA (lncRNA) XIST has been implicated in the progression of a variety of tumor diseases. The purpose of this study was to explore the molecular role of lncRNA XIST in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS The expression levels of lncRNA XIST, miR-192 and TRIM25 in HBV-related HCC tissues and HepG2.2.15 cells were detected by qRT-PCR. Biological information and luciferin gene reporter assay were performed to detect the interaction among lncRNA XIST, miR-192 and TRIM25. CCk-8 assay, wound healing assay and colony formation assay were conducted to detect the proliferation and migration ability of HepG2.2.15 cells. RESULTS qRT-PCR results showed that the expression levels of lncRNA XIST were remarkably increased in HBV-related HCC tissues and HepG2.2.15 cells. In addition, miR-192 was a direct target gene of lncRNA XIST, and the expression of miR-192 and lncRNA XIST were negatively correlated. Moreover, overexpression of miR-192 observably inhibited the proliferation and migration of HCC cells, while overexpression of lncRNA XIST showed an opposite effect. Furthermore, TRIM25 was a direct target of miR-192, and lncRNA XIST could up-regulate the expression of TRIM25 by targeting miR-192. CONCLUSION LncRNA XIST could up-regulate the expression of TRIM25 by targeting and binding to miR-192, thus accelerating the occurrence and development of HCC.
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Affiliation(s)
- Jiancheng Wang
- The People's Hospital of Lianshui County, Huai'an City, 223400, Jiangsu Province, People's Republic of China
| | - Gang Yin
- Department of Intervention, The Second People's Hospital of Huai'an City, Huai'an City, 223002, Jiangsu Province, People's Republic of China
| | - Hu Bian
- Department of Pain and Intervention, Huaiyin Hospital of Huai'an City, Huai'an City, 223300, Jiangsu Province, People's Republic of China
| | - Jiangli Yang
- Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China
| | - Pengcheng Zhou
- Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China
| | - Kai Yan
- Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China
| | - Cheng Liu
- Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China
| | - Pei Chen
- Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China
| | - Jun Zhu
- The Third People's Hospital of Yancheng City, No. 75 Juchang Road, Yancheng City, 224001, Jiangsu Province, People's Republic of China
| | - Zhi Li
- Department of Interventional Radiology, First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Soochow City, 215006, Jiangsu Province, People's Republic of China
| | - Tongqing Xue
- Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China.
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Tortora F, Calin GA, Cimmino A. Effects of long non-coding RNAs on androgen signaling pathways in genitourinary malignancies. Mol Cell Endocrinol 2021; 526:111197. [PMID: 33577974 DOI: 10.1016/j.mce.2021.111197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/01/2021] [Indexed: 11/28/2022]
Abstract
The non-coding RNA (ncRNA) are generally classified, based on length, into small ncRNAs less than 200 nucleotides, such as miRNA, and long ncRNA (lnRNA) with more than 200 nucleotides. The transcription of ncRNAs, similarly to genes that code for proteins, is highly deregulated in cancer. Their expression level can influence physiological processes, e.g. epigenetic regulation of gene expression, regulation of cell cycle and modification of chromatin. Recent studies on androgen receptor in oncology revealed that it exerts a pivotal role in genitourinary malignancies, in particular in prostate tumor was demonstrated that its deregulation takes part in all stages of carcinogenesis. Here, we discuss present learning of the main lnRNAs involvement on androgen signaling pathways in genitourinary neoplasms, highlighting lnRNAs potential in the regulating network comfortable to cancer onset and progression, and discuss the lnRNAs prognostic and diagnostic value in cancer management.
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Affiliation(s)
- Fabiana Tortora
- Institute of Protein Biochemistry, National Research Council, 80131, Naples, Italy.
| | - George A Calin
- Translational Molecular Pathology Department and Leukemia Department, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Amelia Cimmino
- Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council (CNR), Naples, Italy.
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Yang Y, Liu KY, Liu Q, Cao Q. Androgen Receptor-Related Non-coding RNAs in Prostate Cancer. Front Cell Dev Biol 2021; 9:660853. [PMID: 33869227 PMCID: PMC8049439 DOI: 10.3389/fcell.2021.660853] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/12/2021] [Indexed: 12/20/2022] Open
Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related death among men in the United States. Androgen receptor (AR) signaling is the dominant oncogenic pathway in PCa and the main strategy of PCa treatment is to control the AR activity. A large number of patients acquire resistance to Androgen deprivation therapy (ADT) due to AR aberrant activation, resulting in castration-resistant prostate cancer (CRPC). Understanding the molecular mechanisms underlying AR signaling in the PCa is critical to identify new therapeutic targets for PCa patients. The recent advances in high-throughput RNA sequencing (RNA-seq) techniques identified an increasing number of non-coding RNAs (ncRNAs) that play critical roles through various mechanisms in different diseases. Some ncRNAs have shown great potentials as biomarkers and therapeutic targets. Many ncRNAs have been investigated to regulate PCa through direct association with AR. In this review, we aim to comprehensively summarize recent findings of the functional roles and molecular mechanisms of AR-related ncRNAs as AR regulators or targets in the progression of PCa.
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Affiliation(s)
- Yongyong Yang
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Kilia Y Liu
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Qi Liu
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Qi Cao
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.,Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
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Li Y, Zu X, Hu X, Zhao C, Mo M, Fan B. Competing endogenous RNA network analysis reveals pivotal ceRNAs in bladder urothelial carcinoma. Transl Androl Urol 2021; 10:797-808. [PMID: 33718081 PMCID: PMC7947459 DOI: 10.21037/tau-20-1167] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Background Bladder urothelial cancer (BUC) has become one of the most frequently occurring malignant tumors worldwide and it is of great importance to explore the molecular pathogenesis of bladder cancer. Emerging evidence has demonstrated that dysregulation of noncoding RNAs is critically involved in the tumorigenesis and progression of BUC. Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression and therefore form a competing endogenous RNA (ceRNA) network. ceRNA networks have been proven to play vital roles during tumorigenesis and progression. Elements involved in the ceRNA network have also been identified as potential therapeutic targets and prognostic biomarkers in various tumors. Understanding the regulatory mechanisms and functional roles of the ceRNA system will help understand tumorigenesis, progression mechanisms of BUC and develop therapeutics against cancer. Methods In this study, we utilized the TCGA database and analyzed the multilevel expression profile of BUC. ceRNA regulatory networks were constructed by integrating tumor progression and prognosis information. RNA immunoprecipitation (RIP) and qRT-PCR were applied to verify the identified ceRNA networks. KEGG enrichment analysis was implemented to infer the biological functions of the regulatory system. Results We identified a lncRNA-miRNA-mRNA regulatory ceRNA network containing two lncRNAs, one miRNA and 14 mRNAs. The ceRNA network we identified showed significant roles in BUC tumorigenesis, progression, and metastases. Conclusions The proposed ceRNA network may help explain the regulatory mechanism by which lncRNAs function as ceRNAs and improve our understanding of the pathogenesis of BUC. Moreover, the candidate elements involved in the ceRNA network can be further evaluated as potential therapeutic targets and prognostic biomarkers for BUC.
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Affiliation(s)
- Yangle Li
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiongbing Zu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiheng Hu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Cheng Zhao
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Miao Mo
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
| | - Benyi Fan
- Department of Urology, Xiangya Hospital, Central South University, Changsha, China
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The Role of MiR-124 in Bladder Cancer – A Review of the Literature. REV ROMANA MED LAB 2021. [DOI: 10.2478/rrlm-2021-0001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
MicroRNAs (miRNAs) are a group of non-coding RNA molecules that have an important role in modulating the expression of genes involved in regulating cellular functions. A growing number of studies suggest the abnormal expression of microRNAs in different types of cancer cells. MiRNA-124 is a microRNA that is down-regulated in many types of cancer cells, including bladder cancer. Our objective is to provide a review of the key publications that studied the effect of miR-124 on bladder cancer. This review focus on the targets and different pathways of miR-124 that were identified in various studies and differences between their expressions in normal urothelium and tumor tissues. We also include data regarding urinary methylations levels of miR-124 and their role in bladder cancer diagnosis and prognosis. Subsequently, we establish future perspectives of miR-124 research and its promising role in bladder cancer.
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A 5-lncRNA Signature Associated with Smoking Predicts the Overall Survival of Patients with Muscle-Invasive Bladder Cancer. DISEASE MARKERS 2021; 2021:8839747. [PMID: 33688381 PMCID: PMC7914096 DOI: 10.1155/2021/8839747] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 10/25/2020] [Accepted: 11/25/2020] [Indexed: 12/13/2022]
Abstract
Increasing evidence demonstrated that noncoding RNA is abnormally expressed in cancer tissues and serves a vital role in tumorigenesis, tumor development, and metastasis. The aim of the present study was to determine an lncRNA signature in order to predict the overall survival (OS) of patients with muscle-invasive bladder cancer (MIBC). A total of 246 patients with pathologically confirmed MIBC in The Cancer Genome Atlas (TCGA) dataset were recruited and included in the present study. We choose patients who have smoked less (including never smoking) or more than 15 years. A total of 44 differentially expressed lncRNAs were identified with a fold change larger than 1.5 and a P value < 0.05 through the limma package. Subsequently, a comparison between patients with no tobacco smoke exposure for <15 years and patients who had been exposed to tobacco smoke for >15 years was performed by using the matchIt package. Among the 44 differentially expressed lncRNAs, 5 lncRNAs were identified to be significantly associated with OS. Based on the characteristic risk scores of these 5 lncRNAs, patients were divided into low-risk and high-risk groups and exhibited significant differences in OS. Multivariate Cox regression analysis demonstrated that the 5-lncRNA signature was independent of age, tumor-node metastasis (TNM) staging, lymphatic node status, and adjuvant postoperative radiotherapy. In the present study, a novel 5-lncRNA signature was developed and was demonstrated to be useful in predicting the survival of patients with MIBC. If validated, this lncRNA signature may assist in the selection of a high-risk subpopulation that requires more aggressive therapeutic intervention. The risk scores involved in several associated pathways were identified using gene set enrichment analysis (GSEA). However, the clinical implications and mechanism of these 5 lncRNAs require further investigation.
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Ghafouri-Fard S, Shoorei H, Bahroudi Z, Abak A, Majidpoor J, Taheri M. An update on the role of miR-124 in the pathogenesis of human disorders. Biomed Pharmacother 2021; 135:111198. [PMID: 33412388 DOI: 10.1016/j.biopha.2020.111198] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/01/2020] [Accepted: 12/26/2020] [Indexed: 12/28/2022] Open
Abstract
MicroRNA-124 (miR-124) is a copious miRNA in the brain, but it is expressed in a wide range of human/animal tissues participating in the pathogenesis of several disorders. Based on its important function in the development of the nervous system, abnormal expression of miR-124 has been detected in nervous system diseases including Alzheimer's disease, Parkinson's disease, Hypoxic-Ischemic Encephalopathy, Huntington's disease, and ischemic stroke. In addition to these conditions, miR-124 contributes to the pathogenesis of cardiovascular disorders, hypertension, and atherosclerosis. Besides, it has been shown to be down-regulated in a wide range of human cancers such as colorectal cancer, breast cancer, gastric cancer, glioma, pancreatic cancer, and other types of cancer. Yet, few studies have reported upregulation of miR-124 in some cancer types. In the current study, we describe the role of miR-124 in these malignant and non-malignant conditions.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Shoorei
- Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Zahra Bahroudi
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Atefe Abak
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jamal Majidpoor
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Liu Q, Ran R, Wu Z, Li X, Zeng Q, Xia R, Wang Y. Long Non-coding RNA X-Inactive Specific Transcript Mediates Cell Proliferation and Intrusion by Modulating the miR-497/Bcl-w Axis in Extranodal Natural Killer/T-cell Lymphoma. Front Cell Dev Biol 2020; 8:599070. [PMID: 33364236 PMCID: PMC7753184 DOI: 10.3389/fcell.2020.599070] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 11/11/2020] [Indexed: 11/25/2022] Open
Abstract
The present study was directed toward laying new findings for Extranodal natural killer/T-cell lymphoma (ENKL)-oriented therapy with a focus on long non-coding RNA (lncRNA)–microRNAs (miRNAs)–mRNA interaction. The expression and function of XIST (X-inactive specific transcript) were analyzed both in vivo and in vitro. The online database of lncRNA-miRNA interaction was used to screen the target of XIST, and miR-497 was selected. Next, the predicted binding between XIST and miR-497, and the dynamic effect of XIST and miR-497 on downstream Bcl-w was evaluated. We found that XIST dramatically increased in the blood of ENKL patients and cell lines. XIST knockdown suppressed the cell proliferation and migration in vivo and in vitro. Herein, we confirmed the negative interaction between XIST and miR-497. Moreover, XIST knockdown reduced the protein levels of Bcl-w, a downstream target of miR-497. XIST sponges miR-497 to promote Bcl-w expression, and finally modulating ENKL cell proliferation and migration. To be interested, inhibition of Bcl-w by ABT737 can overcome the high expression of XIST, and suppressed the ENKL proliferation and migration by inducing apoptosis. This study provided a novel experimental basis for ENKL-oriented therapy with a focus on the lncRNA–miRNA–mRNA interaction.
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Affiliation(s)
- Qinhua Liu
- Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ruonan Ran
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhengsheng Wu
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xiaodan Li
- Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qingshu Zeng
- Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ruixiang Xia
- Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yalei Wang
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Li P, Wang L, Li P, Hu F, Cao Y, Tang D, Ye G, Li H, Wang D. Silencing lncRNA XIST exhibits antiproliferative and proapoptotic effects on gastric cancer cells by up-regulating microRNA-132 and down-regulating PXN. Aging (Albany NY) 2020; 13:14469-14481. [PMID: 33154189 PMCID: PMC8202840 DOI: 10.18632/aging.103635] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 06/25/2020] [Indexed: 02/07/2023]
Abstract
The present study aims to elucidate the potential therapeutic role of lncRNA XIST in gastric cancer through regulation of microRNA-132 (miR-132) and paxillin (PXN) expression. The study employed 65 gastric cancer tissue specimens and SGC7901 cell lines. Our results demonstrated that expression of lncRNA XIST and PXN was significantly elevated while the expression of miR-132 was significantly reduced in gastric cancer tissues. Dual-luciferase, RNA pull-down and RIP assays demonstrated that lncRNA XIST up-regulated the PXN expression by competitively binding to miR-132. Moreover, silencing of lncRNA XIST and up-regulation of miR-132 could suppress tumor formation ability, cell proliferation and migration, but enhanced apoptosis in gastric cancer. However, the overexpression of PXN achieved the opposite tumor-promotive effect. Meanwhile, rescue experiments suggested that silencing of lncRNA XIST could reverse the tumor-promotive effect exerted by either miR-132 inhibitor or PXN. Taken together, the present study demonstrates lncRNA XIST as a novel oncogenic lncRNA in gastric cancer, highlighting its therapeutic role in this disease.
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Affiliation(s)
- Ping Li
- Department of General Surgery, Huaian Tumor Hospital, Huaian Hospital of Huaian City, Huaian, 223200, P.R. China
- Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University, Mannheim 68167, Germany
| | - Liuhua Wang
- Department of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Institute of General Surgery - Yangzhou, Yangzhou University, Yangzhou 225000, P.R. China
| | - Pengfei Li
- Department of General Surgery, Huaian Tumor Hospital, Huaian Hospital of Huaian City, Huaian, 223200, P.R. China
| | - Fangyong Hu
- Department of General Surgery, Huaian Tumor Hospital, Huaian Hospital of Huaian City, Huaian, 223200, P.R. China
| | - Yi Cao
- Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University, Mannheim 68167, Germany
| | - Dong Tang
- Department of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Institute of General Surgery - Yangzhou, Yangzhou University, Yangzhou 225000, P.R. China
| | - Gang Ye
- Department of General Surgery, Jiangdu People's Hospital of Yangzhou, Yangzhou 225200, P.R. China
| | - Hongbo Li
- Department of General Surgery, Jiangdu People's Hospital of Yangzhou, Yangzhou 225200, P.R. China
| | - Daorong Wang
- Department of General Surgery, Northern Jiangsu Province Hospital, Clinical Medical College, Institute of General Surgery - Yangzhou, Yangzhou University, Yangzhou 225000, P.R. China
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Xu Y, Liu N, Wei Y, Zhou D, Lin R, Wang X, Shi B. Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells. Aging (Albany NY) 2020; 12:19660-19676. [PMID: 33040049 PMCID: PMC7732307 DOI: 10.18632/aging.103997] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 08/05/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This study aims to explore the roles of miR-124 in pancreatic tumor and potential vehicles. RESULTS The miR-124 expression levels decreased in pancreatic adenocarcinoma tissues and cancer cell lines AsPC-1, PANC1, BxPC-3 and SW1990. Furthermore, the elevated expression of miR-124 in AsPC-1 and PANC1 via miR-124 mimic transfection-induced apoptosis, metastasis and epithelial mesenchymal transition was suppressed, and the EZH2 overexpression partly reversed the protective effects of miR-124 against pancreatic tumors. In addition, the expression of miR-124 was detected in exosomes extracted from miR-124-transfected BM-MSCs, and these exosomes delivered miR-124 into pancreatic cancer cells, and presented the anti-tumor effects in vitro and in vivo. CONCLUSION MiR-124-carried BM-MSC-derived exosomes have potential applications for the treatment of pancreatic tumors. METHODS The expression of miR-124 and EZH2 was determined in both pancreatic cancer tissues and cell lines. miR-124 or EZH2 was overexpressed in AsPC-1 and PANC1 cells. Then, the effects on cell viability. apoptosis, invasion, migration and epithelial mesenchymal transition were evaluated. Afterwards, the roles of miR-124 on the expression and function of EZH2 in pancreatic tumors were determined by dual luciferase reporter assay. Subsequently, miR-124 was transfected to bone marrow mesenchymal stromal cells (BM-MSCs), and the BM-MSCs derived exosomes were isolated and co-cultured with AsPC-1 and PANC1 cells, or injected into pancreatic cancer tumor-bearing mice.
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Affiliation(s)
- Yan Xu
- Department of General Surgery, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
| | - Nanbin Liu
- Department of General Surgery, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
| | - Yuhua Wei
- Department of General Surgery, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
| | - Deren Zhou
- Department of General Surgery, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
| | - Rui Lin
- Department of General Surgery, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
| | - Xiuyan Wang
- Department of Ultrasonography, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
| | - Baomin Shi
- Department of General Surgery, Tongji Hospital, Tongji University Medical School, Shanghai 200065, China
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Wei X, Wang B, Wang Q, Yang X, Yang Y, Fang Z, Yi C, Shi L, Fan X, Tao J, Guo Y, Song D. MiR-362-5p, Which Is Regulated by Long Non-Coding RNA MBNL1-AS1, Promotes the Cell Proliferation and Tumor Growth of Bladder Cancer by Targeting QKI. Front Pharmacol 2020; 11:164. [PMID: 32194406 PMCID: PMC7063466 DOI: 10.3389/fphar.2020.00164] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 02/07/2020] [Indexed: 11/13/2022] Open
Abstract
In this study, we found miR-362-5p was upregulated in bladder cancer tissues and we predicted that QKI is potential a target of miR-362-5p and MBNL1-AS1 might be able to directly target to miR-362-5p. We attempted to evaluate whether miR-362-5p could play its roles in bladder cancer through regulating QKI (quaking) and whether the expression and function of miR-362-5p could be mediated by lncRNA MBNL1-AS1. We performed the gain- and loss-function experiments to explore the association between miR-362-5p expression and bladder cancer proliferation. In vivo, the nude mice were injected with miR-362-5p knockdown SW780 cells to assess the effects of miR-362-5p on tumor growth. The results showed upregulation of miR-362-5p promoted cell proliferation of bladder cancer cells. MBNL1-AS1 and QKI could directly bind with miR-362-5p, and knockdown of MBNL1-AS1 or QKI could abrogate the regulatory effects of miR-362-5p on bladder cancer cell proliferation. Furthermore, downregulation of miR-362-5p inhibited bladder tumor growth and increased QKI expression. Our data unveiled that miR-362-5p may play an oncogenic role in bladder cancer through QKI and MBNL1-AS1 might function as a sponge to mediate the miR-362-5p expression and function.
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Affiliation(s)
- Xiaosong Wei
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Beibei Wang
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qi Wang
- College of Science, The Australian National University, Canberra, ACT, Australia
| | - Xiaoming Yang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yang Yang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhiwei Fang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chengzhi Yi
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lei Shi
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xin Fan
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jin Tao
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yufeng Guo
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dongkui Song
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Li X, Hou L, Yin L, Zhao S. LncRNA XIST interacts with miR-454 to inhibit cells proliferation, epithelial mesenchymal transition and induces apoptosis in triple-negative breast cancer. J Biosci 2020. [DOI: 10.1007/s12038-020-9999-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Yang LG, Cao MZ, Zhang J, Li XY, Sun QL. LncRNA XIST modulates HIF-1A/AXL signaling pathway by inhibiting miR-93-5p in colorectal cancer. Mol Genet Genomic Med 2020; 8:e1112. [PMID: 32061057 PMCID: PMC7196477 DOI: 10.1002/mgg3.1112] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 12/02/2019] [Indexed: 12/17/2022] Open
Abstract
Background Long noncoding RNA (LncRNA) XIST is one of the genes that exists in different types of cancers. Earlier researches showed that XIST can advance the progression of colorectal cancer. Nevertheless, the potential molecular mechanism of XIST in combination with miR‐93‐5p has not been explored in colorectal cancer. Methods We performed qRT‐PCR to explore the level of XIST. And a serious experiments in vitro and in vivo were performed to explore the function of XIST. The relationship between XIST/HIF‐1A and miR‐93‐5p was confirmed by RIP and dual‐luciferase assays. Results In the present research, our team demonstrated the upregulation of XIST expression, which was related to tumor progression, and the downregulation of miR‐93‐5p in cells and tissues of colorectal cancer. XIST is the competitive endogenous RNA of miR‐93‐5p to promote HIF‐1A, and then the upregulated AXL level facilitates the EMT process, migration, and proliferation of colorectal cancer. At last, we proved that XIST enhanced the in vivo and in vitro activities of colorectal cancer by regulating AXL signaling. Conclusion In summary, the above results indicate that XIST promotes colorectal cancer tumorigenesis by regulating miR‐93‐5p/HIF‐1A/AXL signaling pathway, which will supply a novel perspective to diagnose and treat colorectal cancer disease.
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Affiliation(s)
- Li-Guang Yang
- Department of Gastrointestinal Surgery, Linyi Central Hospital, Linyi, China
| | - Ming-Zheng Cao
- Department of Gastrointestinal Surgery, Linyi Central Hospital, Linyi, China
| | - Jie Zhang
- Department of Gastrointestinal Surgery, Linyi Central Hospital, Linyi, China
| | - Xiao-Yan Li
- Department of Gastrointestinal Surgery, Linyi Central Hospital, Linyi, China
| | - Qin-Li Sun
- Department of Gastrointestinal Surgery, Linyi Central Hospital, Linyi, China
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Abstract
Long non-coding RNAs (lncRNAs) are regulators of cellular machinery that are commonly dysregulated in genitourinary malignancies. Accordingly, the investigation of lncRNAs is improving our understanding of genitourinary cancers, from development to progression and dissemination. lncRNAs are involved in major oncogenic events in genitourinary malignancies, including androgen receptor (AR) signalling in prostate cancer, hypoxia-inducible factor (HIF) pathway activation in renal cell carcinoma and invasiveness in bladder cancer, as well as multiple other proliferation and survival mechanisms. In line with their putative oncogenic roles, new lncRNA-based classifications are emerging as potent predictors of prognosis. In clinical practice, detection of oncogenic lncRNAs in serum or urine might enable early cancer detection, and lncRNAs might also be promising therapeutic targets for patients with genitourinary cancer. Furthermore, as predictors of sensitivity to anticancer treatments, lncRNAs could be integrated into future precision medicine strategies. Overall, lncRNAs are promising new candidates for molecular studies and for discovery of innovative biomarkers and are putative therapeutic targets in genitourinary oncology.
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Zheng Y, Nie P, Xu S. Long noncoding RNA linc00467 plays an oncogenic role in hepatocellular carcinoma by regulating the miR-18a-5p/NEDD9 axis. J Cell Biochem 2020; 121:3135-3144. [PMID: 31916278 DOI: 10.1002/jcb.29581] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 12/09/2019] [Indexed: 01/01/2023]
Abstract
Increasing evidence has shown that numerous long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis. Herein, we investigated the biological role of lncRNA linc00467 in the cancer biology of hepatocellular carcinoma (HCC). We observed that linc00467 was upregulated in HCC tissues and cells. Silencing of linc00467 using small interfering RNA interference significantly inhibited the growth and motility of HCC cells, and increased cell apoptosis through regulating the Bcl-2/Bax axis and the caspase cascade, suggesting that linc00467 exerted oncogenic functions in the progression of HCC. Moreover, we found that linc00467 could target miR-18a-5p, and NEDD9 was a target for miR-18a-5p in HCC cells. Furthermore, either the miR-18a-5p inhibitor or upregulation of NEDD9 could recover the inhibitory effects caused by silencing of linc00467. In conclusion, our data highlighted the oncogenic role of linc00467 in HCC progression by regulating the miR-18a-5p/NEDD9 axis.
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Affiliation(s)
- Yuanwen Zheng
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Peihua Nie
- Department of Ophthalmology and otorhinolaryngology, Shandong Provincial Third Hospital, Jinan, China
| | - Shifeng Xu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
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Cui Y, Lu C, Zhang Z, Mao A, Feng L, Fu L, Gu F, Ma X, He D. A Long Non-coding RNA Lnc712 Regulates Breast Cancer Cell Proliferation. Int J Biol Sci 2020; 16:162-171. [PMID: 31892853 PMCID: PMC6930380 DOI: 10.7150/ijbs.36429] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 07/29/2019] [Indexed: 12/22/2022] Open
Abstract
Great quantity of intergenic noncoding RNAs (lncRNAs) have been identified in the mammalian genome and involved in various biological processes, especially in the development and metastasis of cancer. In this study, we identified one lncRNA, lncRNA NONHSAT028712 (Lnc712), was highly expressed in breast cancer cell lines and tissues based on microarray screening. Knockdown of Lnc712 largely inhibited breast cancer cell proliferation. Mechanistically, Lnc712 bound specifically to heat-shock protein 90 (HSP90). Interaction between Lnc712 and HSP90 is required for HSP90 binding to cell division cycle 37 (Cdc37). The Lnc712/HSP90/Cdc37 complex regulated cyclin-dependent kinase 2 (CDK2) activation and then triggered breast cancer cell proliferation. In summary, our results identified a new lncRNA regulate breast cancer proliferation though interaction with HSP90.
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Affiliation(s)
- Yue Cui
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Chunxiao Lu
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Zhiming Zhang
- School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Aiqin Mao
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Lei Feng
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Li Fu
- Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.,✉ Corresponding authors: Dongxu He, Ph.D. School of Food Science and Technology, Jiangnan University, Wuxi, China. ; Xin Ma, Ph.D. Wuxi School of Medicine, Jiangnan University, Wuxi, China. ; Feng Gu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China. ; Li Fu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
| | - Feng Gu
- Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.,✉ Corresponding authors: Dongxu He, Ph.D. School of Food Science and Technology, Jiangnan University, Wuxi, China. ; Xin Ma, Ph.D. Wuxi School of Medicine, Jiangnan University, Wuxi, China. ; Feng Gu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China. ; Li Fu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
| | - Xin Ma
- Wuxi School of Medicine, Jiangnan University, Wuxi, China.,✉ Corresponding authors: Dongxu He, Ph.D. School of Food Science and Technology, Jiangnan University, Wuxi, China. ; Xin Ma, Ph.D. Wuxi School of Medicine, Jiangnan University, Wuxi, China. ; Feng Gu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China. ; Li Fu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
| | - Dongxu He
- School of Food Science and Technology, Jiangnan University, Wuxi, China.,✉ Corresponding authors: Dongxu He, Ph.D. School of Food Science and Technology, Jiangnan University, Wuxi, China. ; Xin Ma, Ph.D. Wuxi School of Medicine, Jiangnan University, Wuxi, China. ; Feng Gu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China. ; Li Fu, M.D. Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
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Wu SQ, He HQ, Kang Y, Xu R, Zhang L, Zhao XK, Zhu X. MicroRNA-200c affects bladder cancer angiogenesis by regulating the Akt2/mTOR/HIF-1 axis. Transl Cancer Res 2019; 8:2713-2724. [PMID: 35117029 PMCID: PMC8798978 DOI: 10.21037/tcr.2019.10.23] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 10/10/2019] [Indexed: 11/25/2022]
Abstract
Background Bladder cancer is one of the most frequent urologic tumours in the world. MicroRNA-200c (miR-200c) has been considered a regulator of tumour angiogenesis. Akt2/mTOR was considered a regulator of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α). However, the mechanism by which miR-200c regulates bladder cancer angiogenesis remains unknown. Methods Western blotting and qRT-PCR were used to detect the expression of protein and mRNA, respectively. Cell proliferation, migration and invasion were detected using MTT, wound-healing and transwell assays, respectively. A dual luciferase reporter assay was used to identify the binding site between miR-200c and Akt2. A tube formation assay was also applied to detect the angiogenesis ability. Results Significantly higher expression levels of HIF-1α and VEGF and lower levels of miR-200c were observed in three types of bladder cancer cell lines. Transfection with the miR-200c mimic markedly inhibited cell viability, angiogenesis, and the expression of VEGF and HIF-1α. Overexpression of miR-200c remarkably suppressed the expression of Akt2, and the binding site between them was identified. Knockdown of Akt2 remarkably decreased the expression of VEGF and HIF-1α by regulating mTOR. miR-200c influenced the expression of VEGF and HIF-1α through the Akt2/mTOR signalling pathway and further regulated angiogenesis in bladder cancer cells. Conclusions We proved that miR-200c could suppress HIF-1α/VEGF expression in bladder cancer cells and inhibit angiogenesis, and these regulations were achieved by targeting Akt2/mTOR. This study may provide new insight into the prevention and treatment of bladder cancer.
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Affiliation(s)
- Shui-Qing Wu
- Department of Urology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Hai-Qing He
- Department of Urology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Ye Kang
- Department of Urology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Ran Xu
- Department of Urology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Lei Zhang
- Department of Urology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Xiao-Kun Zhao
- Department of Urology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
| | - Xuan Zhu
- Department of Urology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
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Yue D, Guanqun G, Jingxin L, Sen S, Shuang L, Yan S, Minxue Z, Ping Y, Chong L, Zhuobo Z, Yafen W. Silencing of long noncoding RNA XIST attenuated Alzheimer's disease-related BACE1 alteration through miR-124. Cell Biol Int 2019; 44:630-636. [PMID: 31743528 DOI: 10.1002/cbin.11263] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 11/14/2019] [Indexed: 12/31/2022]
Abstract
Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. However, its pathogenetic mechanism is still poorly understood. An increasing number of studies have evidenced the important role of long noncoding RNAs (lncRNAs) in AD. The aim of the current study was to investigate the effect and molecular mechanism of the lncRNA X-inactive specific transcript (XIST) in AD. Bilateral common carotid artery occlusion (2VO) was used to induce an AD model in mice. Hydrogen peroxide (H2 O2 ) was used to induce an AD model in N2a cells. The lncRNA XIST, miR-124, and BACE1 messenger RNA expression levels were detected by a real-time polymerase chain reaction. The BACE1 protein expression level was detected by western blot and immunofluorescence assay. The Aβ1-42 expression level was detected using an enzyme-linked immunosorbent assay kit. The expression level of lncRNA XIST was significantly upregulated in AD models, both in vivo and in vitro. Silencing of lncRNA XIST negatively regulated miR-124 and positively regulated BACE1 expression in N2a cells, which is attenuated by cotransfection of anti-miR-124 oligodeoxyribonucleotide (AMO-124). Silencing of lncRNA XIST reversed the effect of H2 O2 on miR-124, BACE1, and Aβ1-42 expression in N2a cells, which was reversed by cotransfection of AMO-124. Silencing of lncRNA XIST attenuated AD-related BACE1 alteration through miR-124. LncRNA XIST may be a new potential target for the treatment of AD.
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Affiliation(s)
- Du Yue
- Harbin Medical University Fourth Hospital, Neurology, Harbin, 150001, China
| | - Gao Guanqun
- Harbin Medical University Fourth Hospital, Neurology, Harbin, 150001, China
| | - Li Jingxin
- Heilongjiang Provincial Hospital, Neurology, Harbin, Heilongjiang, 150030, China
| | - Suo Sen
- Harbin Medical University Fourth Hospital, Neurology, Harbin, 150001, China
| | - Liu Shuang
- Heilongjiang Provincial Hospital, Neurology, Harbin, Heilongjiang, 150030, China
| | - Sun Yan
- Harbin Medical University Fourth Hospital, Neurology, Harbin, 150001, China
| | - Zhang Minxue
- Harbin Medical University Fourth Hospital, Neurology, Harbin, 150001, China
| | - Yin Ping
- Heilongjiang Provincial Hospital, Neurology, Harbin, Heilongjiang, 150030, China
| | - Lu Chong
- Heilongjiang Provincial Hospital, Neurology, Harbin, Heilongjiang, 150030, China
| | - Zhang Zhuobo
- Harbin Medical University Fourth Hospital, Neurology, Harbin, 150001, China
| | - Wei Yafen
- Heilongjiang Provincial Hospital, Neurology, Harbin, Heilongjiang, 150030, China
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Yang Y, Cao Y, Qin G, Wang L, Li Q, Dai S, Guo L, Guo Q, Peng YG, Duan B, Wang E. Long non‐coding RNA expression profiling in the lungs of pulmonary arterial hypertension rats with acute inflammation. Pulm Circ 2019; 9:2045894019879393. [PMID: 35154666 PMCID: PMC8826282 DOI: 10.1177/2045894019879393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 09/07/2019] [Indexed: 11/15/2022] Open
Abstract
Background We performed RNA-sequencing to investigate the changes and expression profiles in long
non-coding RNAs (lncRNAs) and their potential functional roles in the lungs of pulmonary
arterial hypertension rats responding to acute inflammation. Methods To establish a pulmonary arterial hypertension rat model, monocrotaline was injected
intraperitoneally and lipopolysaccharide was given to induce acute inflammation.
Selected lncRNAs were validated by quantitative real-time polymerase chain reaction
(qRT-PCR). Bioinformatics analyses were carried out to predict the potential biological
roles of key lncRNAs. Results Twenty-eight lncRNAs and seven mRNAs with elevated expression and 202 lncRNAs and 36
mRNAs with decreased expression were found in the lung tissues of
lipopolysaccharide-treated pulmonary arterial hypertension rats compared with control
group. The qRT-PCR validation results were consistent with the bioinformatics analysis.
Gene ontology analyses showed that the mRNAs and lncRNAs were differentially expressed
in different pathways regarding biological process, cellular components, and molecular
function. The functions of differentially expressed messenger RNAs (DEmRNAs) and
DElncRNAs were indicated by Kyoto Encyclopedia of Genes and Genomes enrichment. Conclusion The DEmRNAs co-expressed with DElncRNAs were obviously enriched in inflammation.
DElncRNAs and DEmRNAs in the lungs of pulmonary arterial hypertension rats changed with
acute inflammation may provide new insights into the pathogenesis of pulmonary arterial
hypertension.
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Affiliation(s)
- Yue Yang
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Yanan Cao
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Gang Qin
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Lu Wang
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Qian Li
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Sisi Dai
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Lizhe Guo
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Qulian Guo
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - Yong Gang Peng
- Department of AnesthesiologyUniversity of Florida College of MedicineGainesvilleFLUSA
| | - Bin Duan
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
| | - E. Wang
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaPeople's Republic of China
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Li S, Wu X, Pei Y, Wang W, Zheng K, Qiu E, Zhang X. PTHR1 May Be Involved in Progression of Osteosarcoma by Regulating miR-124-3p- AR-Tgfb1i1, miR-27a-3p- PPARG-Abca1, and miR-103/590-3p- AXIN2 Axes. DNA Cell Biol 2019; 38:1323-1337. [PMID: 31536386 DOI: 10.1089/dna.2019.4880] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Our previous study has indicated that the parathyroid hormone type 1 receptor (PTHR1) may play important roles in development and progression of osteosarcoma (OS) by regulating Wnt, angiogenesis, and inflammation pathway genes. The goal of this study was to further illuminate the roles of PTHR1 in OS by investigating upstream regulation mechanisms (including microRNA [miRNA] and transcription factors [TFs]) of crucial genes. The microarray dataset GSE46861 was downloaded from the Gene Expression Omnibus database, in which six tumors with short hairpin RNA (shRNA) PTHR1 knockdown (PTHR1.358) and six tumors with shRNA control knockdown (Ren.1309) were collected from mice. Differentially expressed genes (DEGs) between PTHR1.358 and Ren.1309 were identified using the linear models for microarray data (LIMMA) method, and then the miRNA-TF-mRNA regulatory network was constructed using data from corresponding databases, followed by module analysis, to screen crucial regulatory relationships. OS-related human miRNAs were extracted from the curated Osteosarcoma Database. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. As a result, the miRNA-TF-mRNA regulatory network, including 1049 nodes (516 miRNA, 25 TFs, and 508 DEGs) and 15942 edges (interaction relationships, such as Pparg-Abca1 and miR-590-3p-AXIN2), was constructed, from which three significant modules were extracted and modules 2 and 3 contained interactions between miRNAs/TFs and DEGs such as miR-103-3p-AXIN2, miR-124-3p-AR-Tgfb1i1, and miR-27a-3p-PPARG-Abca1. miR-27a-3p was a known miRNA associated with OS. Abca1, AR, and miR-124-3p were hub genes in the miRNA-TF-mRNA network. Tgfb1i1 was involved in cell proliferation, Abca1 participated in the cholesterol metabolic process, and AXIN2 was associated with the canonical Wnt signaling pathway. Furthermore, we also confirmed upregulation of miR-590-3p and downregulation of AXIN2 in the mouse OS cell line K7M2-WT transfected with PTHR1 shRNA. In conclusion, PTHR1 may play important roles in progression of OS by activating miR-124-3p-AR-Tgfb1i1, miR-27a-3p-PPARG-Abca1, and miR-103/590-3p-AXIN2 axes.
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Affiliation(s)
- Shenglong Li
- Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
| | - Xixi Wu
- School of Medicine, Ross University School of Medicine, Miramar, Florida
| | - Yi Pei
- Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
| | - Wei Wang
- Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
| | - Ke Zheng
- Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
| | - Enduo Qiu
- Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
| | - Xiaojing Zhang
- Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
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HOXA11-AS promotes the migration and invasion of hepatocellular carcinoma cells by inhibiting miR-124 expression by binding to EZH2. Hum Cell 2019; 32:504-514. [DOI: 10.1007/s13577-019-00269-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 06/29/2019] [Indexed: 12/19/2022]
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