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de la Cruz-Ojeda P, Parras-Martínez E, Rey-Pérez R, Muntané J. In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells. World J Gastroenterol 2025; 31:95207. [PMID: 39839902 PMCID: PMC11684161 DOI: 10.3748/wjg.v31.i3.95207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 08/30/2024] [Accepted: 09/12/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide. Sorafenib is still a recommended treatment for a large proportion of patients with advanced HCC. Different patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 cells. AIM To define the long non-codingRNA-microRNA-mRNA (lncRNA-miRNA-mRNA) predicted signatures related to selected hallmarks of cancer (apoptosis, autophagy, cell stress, cell dedifferentiation and invasiveness) in RNAseq studies using Sorafenib-treated HepG2 and SNU449 cells. Various available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 cells. METHODS HepG2 and SNU449 cells were treated with Sorafenib (10 μmol/L) for 24 hours. Total RNA, including small and long RNA, was extracted with a commercial miRNeasy kit. RNAseq was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory axes. RESULTS MALAT, THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7, TIRARP, TFAP4 and FAXDC2 in HepG2 cells. SNHG12, EPB41 L4A-AS1, LINC01578, SNHG12 and GAS5 interacted with let-7b-3p, miR-195-5p and VEGFA in SNU449 cells. The axes MALAT1/hsa-mir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells, whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib treatment. CONCLUSION Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression, whose proteins mainly increased the antitumor effectiveness of the treatment (SMAD7, TIRARP, TFAP4, FAXDC2 and ADRB2). However, the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.
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Affiliation(s)
- Patricia de la Cruz-Ojeda
- Functional Genomics of Solid Tumors Laboratory, Centre de Recherche des Cordeliers, Paris 75006, France
- Department of Oncology Surgery, Cell Therapy and Organ Transplantation, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Seville 41013, Spain
- Biomedical Research Center for Hepatic and Digestive Diseases, CIBERehd, Madrid 28029, Spain
| | - Ester Parras-Martínez
- Department of Oncology Surgery, Cell Therapy and Organ Transplantation, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Seville 41013, Spain
| | - Raquel Rey-Pérez
- Department of Oncology Surgery, Cell Therapy and Organ Transplantation, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Seville 41013, Spain
| | - Jordi Muntané
- Department of Oncology Surgery, Cell Therapy and Organ Transplantation, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Seville 41013, Spain
- Biomedical Research Center for Hepatic and Digestive Diseases, CIBERehd, Madrid 28029, Spain
- Department of Medical Physiology and Biophysics, University of Seville, Seville 41009, Spain
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ZHANG YE, LIANG YANAN, WU YAN, SONG LIWEN, ZHANG ZUWANG. CircTIAM1 overexpression promotes the progression of papillary thyroid cancer by regulating the miR-338-3p/LASP1 axis. Oncol Res 2024; 32:1747-1763. [PMID: 39449799 PMCID: PMC11497179 DOI: 10.32604/or.2024.030945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 11/01/2023] [Indexed: 10/26/2024] Open
Abstract
Background Papillary thyroid cancer (PTC) is the most prevalent histological type of differentiated thyroid malignancy. Circular RNAs (circRNAs) have been implicated in the pathogenesis and progression of various cancers. circTIAM1 (hsa_circ_0061406) is a novel circRNA with aberrant expression in PTC. However, its functional roles in PTC progression remain to be investigated. Methods The expression levels of circTIAM1 in the PTC and the matched para-cancerous tissues were detected by quantitative real-time reverse-transcription PCR (qRT-PCR). The subcellular localization of circTIAM1 was examined by fluorescence in-situ hybridization (FISH). Kaplan-Meier plot was used to analyze the association of clinicopathological features with circTIAM1 expression. Bioinformatics databases were utilized to predict the target miRNAs of circTIAM1 and the downstream target mRNAs. RNA pull-down, RIP assay, and dual-luciferase reporter assay were used to confirm the interactions. Functional experiments, such as CCK-8, EDU staining, and apoptosis assays, as well as in vivo xenograft model were employed to explore the impacts of circTIAM1, miR-338-3p, and LIM/SH3 protein 1 (LASP1) on the malignant phenotype of the PTC cells. Results CircTIAM1 was highly expressed in PTC cells. Moreover, circTIAM1 silencing suppressed the proliferation and invasion of PTC cells in vitro and impaired tumorigenesis in vivo. Furthermore, miR-338-3p was verified as a miRNA target of circTIAM1. LASP1 was also identified as a downstream target of miR-338-3p. The anti-tumorigenic effect of miR-338-3p overexpression and the pro-tumorigenic effect of LASP1 was further explored by functional assays, which demonstrated that circTIAM1 modulated the PTC progression through targeting miR-338-3p/LASP1 axis. Conclusion The overexpression of circTIAM1 is associated with the malignant progression of PTC. A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.
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Affiliation(s)
- YE ZHANG
- School of Medicine and Health, Jiuzhou Polytechnic, Xuzhou, 221113, China
| | - YANAN LIANG
- Department of Oncology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
| | - YAN WU
- Department of Oncology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
| | - LIWEN SONG
- Department of Oncology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
| | - ZUWANG ZHANG
- Department of Oncology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
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Nucera F, Ruggeri P, Spagnolo CC, Santarpia M, Ieni A, Monaco F, Tuccari G, Pioggia G, Gangemi S. MiRNAs and Microbiota in Non-Small Cell Lung Cancer (NSCLC): Implications in Pathogenesis and Potential Role in Predicting Response to ICI Treatment. Int J Mol Sci 2024; 25:6685. [PMID: 38928392 PMCID: PMC11203619 DOI: 10.3390/ijms25126685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.
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Affiliation(s)
- Francesco Nucera
- Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università degli Studi di Messina, 98166 Messina, Italy;
| | - Paolo Ruggeri
- Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università degli Studi di Messina, 98166 Messina, Italy;
| | - Calogera Claudia Spagnolo
- Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, 98122 Messina, Italy; (C.C.S.); (M.S.)
| | - Mariacarmela Santarpia
- Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, 98122 Messina, Italy; (C.C.S.); (M.S.)
| | - Antonio Ieni
- Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Anatomic Pathology, University of Messina, 98100 Messina, Italy; (A.I.); (G.T.)
| | - Francesco Monaco
- Chirurgia Toracica, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università degli Studi di Messina, 98166 Messina, Italy;
| | - Giovanni Tuccari
- Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Anatomic Pathology, University of Messina, 98100 Messina, Italy; (A.I.); (G.T.)
| | - Giovanni Pioggia
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy;
| | - Sebastiano Gangemi
- Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy;
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Retraction: miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2. PLoS Genet 2024; 20:e1011270. [PMID: 38713643 PMCID: PMC11075846 DOI: 10.1371/journal.pgen.1011270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/09/2024] Open
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Brady P, Yousif A, Sasamoto N, Vitonis AF, Fendler W, Stawiski K, Hornstein MD, Terry KL, Elias KM, Missmer SA, Shafrir AL. Plasma microRNA expression in adolescents and young adults with endometriosis: the importance of hormone use. FRONTIERS IN REPRODUCTIVE HEALTH 2024; 6:1360417. [PMID: 38665804 PMCID: PMC11043576 DOI: 10.3389/frph.2024.1360417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 03/25/2024] [Indexed: 04/28/2024] Open
Abstract
Introduction Prior studies have investigated the diagnostic potential of microRNA (miRNA) expression profiles for endometriosis. However, the vast majority of previous studies have only included adult women. Therefore, we sought to investigate differential expression of miRNAs among adolescents and young adults with endometriosis. Methods The Women's Health Study: from Adolescence to Adulthood (A2A) is an ongoing WERF EPHect compliant longitudinal cohort. Our analysis included 64 patients with surgically-confirmed endometriosis (96% rASRM stage I/II) and 118 females never diagnosed with endometriosis frequency matched on age (median = 21 years) and hormone use at blood draw. MicroRNA measurement was separated into discovery (10 cases and 10 controls) and internal replication (54 cases and 108 controls) phases. The levels of 754 plasma miRNAs were assayed in the discovery phase using PCR with rigorous internal control measures, with the relative expression of miRNA among cases vs. controls calculated using the 2-ΔΔCt method. miRNAs that were significant in univariate analyses stratified by hormone use were included in the internal replication phase. The internal replication phase was split 2:1 into a training and testing set and utilized FirePlex miRNA assay to assess 63 miRNAs in neural network analyses. The testing set of the validation phase was utilized to calculate the area under the curve (AUC) of the best fit models from the training set including hormone use as a covariate. Results In the discovery phase, 49 miRNAs were differentially expressed between endometriosis cases and controls. The associations of the 49 miRNAs differed by hormone use at the time of blood draw. Neural network analysis in the testing set of the internal replication phase determined a final model comprising 5 miRNAs (miR-542-3p, let-7b-3p, miR-548i, miR-769-5p, miR-30c-1-3p), yielding AUC = 0.77 (95% CI: 0.67-0.87, p < 0.001). Sensitivity in the testing dataset improved (83.3% vs. 72.2%) while the specificity decreased (58.3% vs. 72.2%) compared to the training set. Conclusion The results suggest that miR-542-3p, let-7b-3p, miR-548i, miR-769-5p, miR-30c-1-3p may be dysregulated among adolescent and young adults with endometriosis. Hormone use was a significant modifier of miRNA dysregulation and should be considered rigorously in miRNA diagnostic studies.
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Affiliation(s)
- Paula Brady
- Columbia University Fertility Center, Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, United States
| | - Abdelrahman Yousif
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences, El Paso, TX, United States
| | - Naoko Sasamoto
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
- Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital, Boston, MA, United States
| | - Allison F. Vitonis
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
- Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital, Boston, MA, United States
| | - Wojciech Fendler
- Department of Biostatistics and Translational Medicine, Medical University of Łódź, Łódź, Poland
| | - Konrad Stawiski
- Department of Biostatistics and Translational Medicine, Medical University of Łódź, Łódź, Poland
| | - Mark D. Hornstein
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
- Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital, Boston, MA, United States
| | - Kathryn L. Terry
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
- Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital, Boston, MA, United States
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Kevin M. Elias
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
| | - Stacey A. Missmer
- Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital, Boston, MA, United States
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
- Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, United States
- Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States
| | - Amy L. Shafrir
- Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women’s Hospital, Boston, MA, United States
- Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, United States
- Department of Nutrition & Public Health, School of Nursing and Health Sciences, Merrimack College, North Andover, MA, United States
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Salehi M, Kamali MJ, Arab D, Safaeian N, Ashuori Z, Maddahi M, Latifi N, Jahromi AM. Exosomal microRNAs in regulation of tumor cells resistance to apoptosis. Biochem Biophys Rep 2024; 37:101644. [PMID: 38298209 PMCID: PMC10827597 DOI: 10.1016/j.bbrep.2024.101644] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 01/06/2024] [Accepted: 01/09/2024] [Indexed: 02/02/2024] Open
Abstract
Exosomes are a type of extracellular vesicle that contains bioactive molecules that can be secreted by most cells. Nevertheless, the content of these cells differs depending on the cell from which they originate. The exosome plays a crucial role in modulating intercellular communication by conveying molecular messages to neighboring or distant cells. Cancer-derived exosomes can transfer several types of molecules into the tumor microenvironment, including high levels of microRNA (miRNA). These miRNAs significantly affect cell proliferation, angiogenesis, apoptosis resistance, metastasis, and immune evasion. Increasing evidence indicates that exosomal miRNAs (exomiRs) are crucial to regulating cancer resistance to apoptosis. In cancer cells, exomiRs orchestrate communication channels between them and their surrounding microenvironment, modulating gene expression and controlling apoptosis signaling pathways. This review presents an outline of present-day knowledge of the mechanisms that affect target cells and drive cancer resistance to apoptosis. Also, our study looks at the regulatory role of exomiRs in mediating intercellular communication between tumor cells and surrounding microenvironmental cells, specifically stromal and immune cells, to evade therapy-induced apoptosis.
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Affiliation(s)
- Mohammad Salehi
- Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
- Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohammad Javad Kamali
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Daniyal Arab
- Department of Human Genetics, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Naghme Safaeian
- Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Zahra Ashuori
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Moein Maddahi
- Faculty of Dentistry, Yeditepe University, Istanbul, Turkey
| | - Narges Latifi
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Iran
| | - Amir Moein Jahromi
- School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
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Safavi P, Moghadam KB, Haghighi Z, Ferns GA, Rahmani F. Interplay between LncRNA/miRNA and TGF-β Signaling in the Tumorigenesis of Gynecological Cancer. Curr Pharm Des 2024; 30:352-361. [PMID: 38303530 DOI: 10.2174/0113816128284380240123071409] [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: 09/26/2023] [Revised: 12/29/2023] [Accepted: 01/02/2024] [Indexed: 02/03/2024]
Abstract
Gynecologic cancers are among the most common malignancies with aggressive features and poor prognosis. Tumorigenesis in gynecologic cancers is a complicated process that is influenced by multiple factors, including genetic mutations that activate various oncogenic signaling pathways, including the TGF-β pathway. Aberrant activation of TGF-β signaling is correlated with tumor recurrence and metastasis. It has been shown that non-coding RNAs (ncRNAs) have crucial effects on cancer cell proliferation, migration, and metastasis. Upregulation of various ncRNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs), has been reported in several tumors, like cervical, ovarian, and endometrial cancers, but their cellular mechanisms remain to be investigated. Thus, recognizing the role of ncRNAs in regulating the TGF-β pathway may provide novel strategies for better treatment of cancer patients. The present study summarizes recent findings on the role of ncRNAs in regulating the TGF-β signaling involved in tumor progression and metastasis in gynecologic cancers.
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Affiliation(s)
- Pegah Safavi
- Department of Medical Radiation, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Kimia Behrouz Moghadam
- Department of Medicinal Chemistry, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
| | - Zahra Haghighi
- Department of Clinical Biochemistry, Kashmar School of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Farzad Rahmani
- Department of Clinical Biochemistry, Kashmar School of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Le MT, Nguyen HT, Nguyen XH, Do XH, Mai BT, Ngoc Nguyen HT, Trang Than UT, Nguyen TH. Regulation and therapeutic potentials of microRNAs to non-small cell lung cancer. Heliyon 2023; 9:e22080. [PMID: 38058618 PMCID: PMC10696070 DOI: 10.1016/j.heliyon.2023.e22080] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 11/02/2023] [Accepted: 11/03/2023] [Indexed: 12/08/2023] Open
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80%-85% of total cases and leading to millions of deaths worldwide. Drug resistance is the primary cause of treatment failure in NSCLC, which urges scientists to develop advanced approaches for NSCLC treatment. Among novel approaches, the miRNA-based method has emerged as a potential approach as it allows researchers to modulate target gene expression. Subsequently, cell behaviors are altered, which leads to the death and the depletion of cancer cells. It has been reported that miRNAs possess the capacity to regulate multiple genes that are involved in various signaling pathways, including the phosphoinositide 3-kinase, receptor tyrosine kinase/rat sarcoma virus/mitogen-activated protein kinase, wingless/integrated, retinoblastoma, p53, transforming growth factor β, and nuclear factor-kappa B pathways. Dysregulation of these signaling pathways in NSCLC results in abnormal cell proliferation, tissue invasion, and drug resistance while inhibiting apoptosis. Thus, understanding the roles of miRNAs in regulating these signaling pathways may enable the development of novel NSCLC treatment therapies. However, a comprehensive review of potential miRNAs in NSCLC treatment has been lacking. Therefore, this review aims to fill the gap by summarizing the up-to-date information on miRNAs regarding their targets, impact on cancer-associated pathways, and prospective outcomes in treating NSCLC. We also discuss current technologies for delivering miRNAs to the target cells, including virus-based, non-viral, and emerging extracellular vesicle-based delivery systems. This knowledge will support future studies to develop an innovative miRNA-based therapy and select a suitable carrier to treat NSCLC effectively.
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Affiliation(s)
- Mai Thi Le
- Vinmec Hi-tech Center, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
- Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi, 100000, Viet Nam
| | - Huyen-Thu Nguyen
- Vinmec Hi-tech Center, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
| | - Xuan-Hung Nguyen
- Vinmec Hi-tech Center, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
- College of Health Sciences, Vin University, Hanoi, 100000, Viet Nam
- Vinmec-VinUni Institute of Immunology, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
| | - Xuan-Hai Do
- Department of Gastroenterology, 108 Military Central Hospital, Hanoi, Viet Nam
| | - Binh Thanh Mai
- Department of Practical and Experimental Surgery, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La, Ha Dong, Hanoi, Viet Nam
| | - Ha Thi Ngoc Nguyen
- Vinmec Hi-tech Center, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
| | - Uyen Thi Trang Than
- Vinmec Hi-tech Center, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
- Vinmec-VinUni Institute of Immunology, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
| | - Thanh-Hong Nguyen
- Vinmec Hi-tech Center, Vinmec Healthcare System, Hanoi, 100000, Viet Nam
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Al-Noshokaty TM, Elballal MS, Helal GK, Abulsoud AI, Elshaer SS, El-Husseiny AA, Fathi D, Abdelmaksoud NM, Abdel Mageed SS, Midan HM, Zaki MB, Abd-Elmawla MA, Rizk NI, Elrebehy MA, Zewail MB, Mohammed OA, Doghish AS. miRNAs driving diagnosis, prognosis and progression in Merkel cell carcinoma. Pathol Res Pract 2023; 249:154763. [PMID: 37595447 DOI: 10.1016/j.prp.2023.154763] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 08/09/2023] [Accepted: 08/12/2023] [Indexed: 08/20/2023]
Abstract
Merkel cell carcinoma (MCC) is a rare, aggressive form of skin malignancy with a high recurrence commonly within two to three years of initial diagnosis. The incidence of MCC has nearly doubled in the past few decades. Options for diagnosing, assessing, and treating MCC are limited. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play an important role in controlling many different aspects of cell biology. Many miRNAs are aberrantly expressed in distinct types of cancer, with some serving as tumor suppressors and others as oncomiRs. Therefore, the future holds great promise for the utilization of miRNAs in enhancing diagnostic, prognostic, and therapeutic approaches for MCC. Accordingly, the goal of this article is to compile, summarize, and discuss the latest research on miRNAs in MCC, highlighting their potential clinical utility as diagnostic and prognostic biomarkers.
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Affiliation(s)
- Tohada M Al-Noshokaty
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Gouda Kamel Helal
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo 11231, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Ahmed I Abulsoud
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Shereen Saeid Elshaer
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Department of Biochemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo 11823, Egypt
| | - Ahmed A El-Husseiny
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829 Cairo, Egypt
| | - Doaa Fathi
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | | | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Heba M Midan
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohamed Bakr Zaki
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt
| | - Mai A Abd-Elmawla
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Nehal I Rizk
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Moataz B Zewail
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Osama A Mohammed
- Department of Clinical Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
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10
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Retraction: Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma. PLoS Genet 2022; 18:e1010552. [PMID: 36525402 PMCID: PMC9757565 DOI: 10.1371/journal.pgen.1010552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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11
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Bontempi G, Terri M, Garbo S, Montaldo C, Mariotti D, Bordoni V, Valente S, Zwergel C, Mai A, Marchetti A, Domenici A, Menè P, Battistelli C, Tripodi M, Strippoli R. Restoration of WT1/miR-769-5p axis by HDAC1 inhibition promotes MMT reversal in mesenchymal-like mesothelial cells. Cell Death Dis 2022; 13:965. [PMID: 36396626 PMCID: PMC9672101 DOI: 10.1038/s41419-022-05398-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 10/28/2022] [Accepted: 11/02/2022] [Indexed: 11/18/2022]
Abstract
Histone acetylation/deacetylation play an essential role in modifying chromatin structure and in regulating cell plasticity in eukaryotic cells. Therefore, histone deacetylase (HDAC) pharmacological inhibitors are promising tools in the therapy of fibrotic diseases and in cancer. Peritoneal fibrosis is a pathological process characterized by many cellular and molecular alterations, including the acquisition of invasive/pro-fibrotic abilities by mesothelial cells (MCs) through induction of mesothelial to mesenchymal transition (MMT). The aim of this study was to characterize the molecular mechanism of the antifibrotic role of HDAC1 inhibition. Specifically, treatment with MS-275, an HDAC1-3 inhibitor previously known to promote MMT reversal, induced the expression of several TGFBRI mRNA-targeting miRNAs. Among them, miR-769-5p ectopic expression was sufficient to promote MMT reversal and to limit MC migration and invasion, whereas miR-769-5p silencing further enhanced mesenchymal gene expression. These results were confirmed by HDAC1 genetic silencing. Interestingly, miR-769-5p silencing maintained mesenchymal features despite HDAC1 inhibition, thus indicating that it is necessary to drive MMT reversal induced by HDAC1 inhibition. Besides TGFBRI, miR-769-5p was demonstrated to target SMAD2/3 and PAI-1 expression directly. When analyzing molecular mechanisms underlying miR-769-5p expression, we found that the transcription factor Wilms' tumor 1 (WT1), a master gene controlling MC development, binds to the miR-769-5p promoter favoring its expression. Interestingly, both WT1 expression and binding to miR-769-5p promoter were increased by HDAC1 inhibition and attenuated by TGFβ1 treatment. Finally, we explored the significance of these observations in the cell-to-cell communication: we evaluated the ability of miR-769-5p to be loaded into extracellular vesicles (EVs) and to promote MMT reversal in recipient mesenchymal-like MCs. Treatment of fibrotic MCs with EVs isolated from miR-769-5p over-expressing MCs promoted the down-regulation of specific mesenchymal targets and the reacquisition of an epithelial-like morphology. In conclusion, we highlighted an HDAC1-WT1-miR-769-5p axis potentially relevant for therapies aimed at counteracting organ fibrosis.
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Affiliation(s)
- Giulio Bontempi
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
- Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense, 292, Rome, 00149, Italy
| | - Michela Terri
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
- Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense, 292, Rome, 00149, Italy
| | - Sabrina Garbo
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Claudia Montaldo
- Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense, 292, Rome, 00149, Italy
| | - Davide Mariotti
- Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense, 292, Rome, 00149, Italy
| | - Veronica Bordoni
- Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense, 292, Rome, 00149, Italy
| | - Sergio Valente
- Department of Drug Chemistry and Technologies, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy
| | - Clemens Zwergel
- Department of Drug Chemistry and Technologies, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy
| | - Antonello Mai
- Department of Drug Chemistry and Technologies, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy
| | - Alessandra Marchetti
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Alessandro Domenici
- Renal Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, 00189, Rome, Italy
| | - Paolo Menè
- Renal Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, 00189, Rome, Italy
| | - Cecilia Battistelli
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy
| | - Marco Tripodi
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
- Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense, 292, Rome, 00149, Italy.
| | - Raffaele Strippoli
- Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
- Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense, 292, Rome, 00149, Italy.
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12
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MicroRNA-769-3p Acts as a Prognostic Factor in Oral Squamous Cell Cancer by Modulating Stromal Genes. Cancers (Basel) 2022; 14:cancers14184373. [PMID: 36139534 PMCID: PMC9496693 DOI: 10.3390/cancers14184373] [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: 05/13/2022] [Revised: 08/23/2022] [Accepted: 09/05/2022] [Indexed: 12/24/2022] Open
Abstract
miR-769-3p expression is suppressed in the stromal subtype of head and neck squamous cell carcinoma (HNSCC); however, its role in stromal HNSCC has not been fully elucidated. To investigate the biological relevance of miR-769-3p in the stromal phenotype, we established oral squamous cell cancer (OSCC) cell lines, namely CAL27, HSC3, and YD8, overexpressing miR-769-3p. miR-769-3p expression was positively and negatively correlated with interferon-gamma-related genes and MYC target gene sets, respectively. miR-769-3p decreased OSCC cell migration and invasion as well as mesenchymal marker expression and increased epithelial marker expression. Moreover, miR-769-3p enhanced OSCC cell sensitivity to 5-fluorouracil. High miR-769-3p expression was associated with good prognosis of HNSCC patients. Collectively, these results suggest that miR-769-3p suppression enhances stromal gene expression and promotes the epithelial-to-mesenchymal transition. Therefore, miR-769-3p may be a potential biomarker of the miRNA phenotype in OSCC patients.
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13
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Ding L, Feng Y, Li L. Circ_0001955 promotes the progression of non-small cell lung cancer via miR-769-5p/EGFR axis. Cell Cycle 2022; 21:2433-2443. [PMID: 35920610 PMCID: PMC9645262 DOI: 10.1080/15384101.2022.2100681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
To elaborate on the role of circular RNA 0001955 (circ_0001955) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells and its underlying mechanism. Circ_0001955 expression in NSCLC was screened out through bioinformatics analysis based on GEO database. Circ_0001955, microRNA-769-5p (miR-769-5p), and epidermal growth factor receptor (EGFR) expression in NSCLC tissues and cell lines was examined using quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation and apoptosis were examined using the CCK-8 method, BrdU experiment and flow cytometry analysis, respectively. Bioinformatics prediction, dual-luciferase reporter gene experiment and RNA immunoprecipitation (RIP) experiments were applied to validate the targeting relationship between miR-769-5p and circ_0001955 and the 3' UTR of EGFR. Pearson's correlation analysis was employed to validate the correlations among them. Circ_0001955 expression was up-regulated in NSCLC tissues and cell lines, and its overexpression was strongly associated with increased tumor TNM stage and lymph node metastasis. Circ_0001955 overexpression enhanced the proliferation and restrained the apoptosis in NSCLC cells, whereas knocking down circ_0001955 exerted the opposite effects. Circ_0001955 directly targeted miR-769-5p and negatively regulated its expression. EGFR, a target gene of miR-769-5p, could be indirectly and positively regulated by circ_0001955. Correlation analysis indicated that circ_0001955 was negatively correlated with miR-769-5p expression, while circ_0001955 was positively correlated with EGFR expression. Circ_0001955 facilitates the proliferation and represses the apoptosis of NSCLC cells by modulating miR-769-5p/EGFR axis.
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Affiliation(s)
- Li Ding
- Department of Respiratory, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Yinan Feng
- Department of Endocrine and Metabolism, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Longguang Li
- Rehabilitation Medicine, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China
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14
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Koh MZ, Ho WY, Yeap SK, Ali NM, Yong CY, Boo L, Alitheen NB. Exosomal-microRNA transcriptome profiling of Parental and CSC-like MDA-MB-231 cells in response to cisplatin treatment. Pathol Res Pract 2022; 233:153854. [PMID: 35398617 DOI: 10.1016/j.prp.2022.153854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 03/17/2022] [Accepted: 03/22/2022] [Indexed: 11/24/2022]
Abstract
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with higher risk of metastasis and cancer reoccurrence. Cisplatin is one of the potential anticancer drugs for treating TNBC, where its effectiveness remains challenged by frequent occurrence of cisplatin resistance. Since acquirement of drug resistance often being associated with presence of cancer stem cells (CSCs), investigation has been conducted, suggesting CSC-like subpopulation to be more resistant to cisplatin than their parental counterpart. On the other hand, plethora evidences showed the transmission of exosomal-miRNAs are capable of promoting drug resistance in breast cancers. In this study, we aim to elucidate the differential expression of exosomal-microRNAs profile and reveal the potential target genes in correlation to cisplatin resistance associated with CSC-like subpopulation by using TNBC cell line (MDA-MB-231). Utilizing next generation sequencing and Nanostring techniques, cisplatin-induced dysregulation of exosomal-miRNAs were evaluated in maximal for CSC-like subpopulation as compared to parental cells. Intriguingly, more oncogenic exosomal-miRNAs profile was detected from treated CSC-like subpopulation, which may correlate to enhancement of drug resistance and maintenance of CSCs. In treated CSC-like subpopulation, unique clusters of exosomal-miRNAs namely miR-221-3p, miR-196a-5p, miR-17-5p and miR-126-3p were predicted to target on six genes (ATXN1, LATS1, GSK3β, ITGA6, JAG1 and MYC), aligned with previous finding which demonstrated dysregulation of these genes in treated CSC-like subpopulation. Our results highlight the potential correlation of exosomal-miRNAs and their target genes as well as novel perspectives of the corresponding pathways that may be essential to contribute to the attenuated cytotoxicity of cisplatin in CSC-like subpopulation.
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Affiliation(s)
- May Zie Koh
- Faculty of Sciences and Engineering, University of Nottingham Malaysia, Semenyih 43500, Malaysia.
| | - Wan Yong Ho
- Faculty of Sciences and Engineering, University of Nottingham Malaysia, Semenyih 43500, Malaysia.
| | - Swee Keong Yeap
- China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Sepang 43900, Malaysia.
| | - Norlaily Mohd Ali
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia.
| | - Chean Yeah Yong
- Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Lily Boo
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Cheras 43000, Malaysia.
| | - Noorjahan Banu Alitheen
- Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.
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15
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Wang L, Zeng C, Chen Z, Qi J, Huang S, Liang H, Huang S, Ou Z. Circ_0025039 acts an oncogenic role in the progression of non-small cell lung cancer through miR-636-dependent regulation of CORO1C. Mol Cell Biochem 2022; 477:743-757. [PMID: 35034254 DOI: 10.1007/s11010-021-04320-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 11/29/2021] [Indexed: 11/28/2022]
Abstract
Non-small cell lung cancer remains the leading cause of cancer-related death worldwide. Circular RNA plays vital roles in NSCLC progression. This study is designed to reveal the role of circ_0025039 in NSCLC cell malignancy. The RNA expression of circ_0025039, microRNA-636 (miR-636), and coronin 1C was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell proliferation, migration, invasion, tube formation ability, sphere formation capacity, and apoptosis were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, transwell assay, tube formation assay, sphere formation assay, and flow cytometry analysis, respectively. Mouse model assay was conducted to reveal the effect of circ_0025039 silencing on tumor formation in vivo. The interaction between miR-636 and circ_0025039 or CORO1C was identified through dual-luciferase reporter and RNA pull-down assays. The expression of circ_0025039 and CORO1C was significantly increased, while miR-636 was decreased in NSCLC tissues and cells compared with controls. Circ_0025039 depletion repressed NSCLC cell proliferation, migration, invasion, tube-forming capacity, and sphere formation ability, but induced cell apoptosis. The neoplasm formation was repressed after circ_0025039 silencing. Additionally, circ_0025039 acted as a sponge for miR-636, which was found to target CORO1C. Importantly, the contribution of circ_0025039 to NSCLC progression was mediated by miR-636/CORO1C axis. Circ_0025039 silencing repressed NSCLC malignant progression by reducing CORO1C expression through miR-636, showing the possibility of circ_0025039 as a therapeutic target for NSCLC.
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Affiliation(s)
- Lei Wang
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China
| | - Cimei Zeng
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China
| | - Zhongren Chen
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China
| | - Jianxu Qi
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China
| | - Sini Huang
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China
| | - Haimei Liang
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China
| | - Shiren Huang
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China
| | - Zongxing Ou
- Department of Respiratory and Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, No. 43, Renmin Avenue, Meilan District, Haikou City, Hainan Province, 570208, PR China.
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16
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Sun Y, Li J, Zheng S. MiR-769-5p, Which Targets HDGF, Inhibits Cell Proliferation and Invasion in Nonsmall Cell Lung Cancer. Cancer Biother Radiopharm 2021. [PMID: 34978893 DOI: 10.1089/cbr.2021.0363] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
MiR-769-5p regulates tumor correlative genes, which plays a critical role in the progression of various types of tumor. However, the precise regulatory mechanism of miR-769-5p on nonsmall cell lung cancer (NSCLC) is unknown. This study was to discover the role and underlying mechanisms of miR-769-5p in NSCLC. MiR-769-5p expression was shown to be reduced, according to our findings. MiR-769-5p overexpression inhibited NSCLC cell proliferation while promoting NSCLC cell apoptosis. Furthermore, NSCLC cell migration and invasion were reduced when miR-769-5p was overexpressed. Furthermore, HDGF was confirmed as a miR-769-5p target gene that was negatively regulated by miR-769-5p. Furthermore, more research revealed that HDGF overexpression reduced the inhibitory effect of miR-769-5p on NSCLC cell biofunction. Finally, miR-769-5p inhibited NSCLC cell proliferation and invasion by targeting HDGF, indicating that NSCLC could benefit from miR-769-5p as a diagnostic and prognostic biomarker.
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Affiliation(s)
- Yuejun Sun
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Cardiothoracic Surgery, Jiangsu Jiangyin People's Hospital, Jiangyin, China
| | - Jie Li
- Department of Respiratory Medicine, Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, China
| | - Shiying Zheng
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Shaw A, Gullerova M. Home and Away: The Role of Non-Coding RNA in Intracellular and Intercellular DNA Damage Response. Genes (Basel) 2021; 12:1475. [PMID: 34680868 PMCID: PMC8535248 DOI: 10.3390/genes12101475] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 12/14/2022] Open
Abstract
Non-coding RNA (ncRNA) has recently emerged as a vital component of the DNA damage response (DDR), which was previously believed to be solely regulated by proteins. Many species of ncRNA can directly or indirectly influence DDR and enhance DNA repair, particularly in response to double-strand DNA breaks, which may hold therapeutic potential in the context of cancer. These include long non-coding RNA (lncRNA), microRNA, damage-induced lncRNA, DNA damage response small RNA, and DNA:RNA hybrid structures, which can be categorised as cis or trans based on the location of their synthesis relative to DNA damage sites. Mechanisms of RNA-dependent DDR include the recruitment or scaffolding of repair factors at DNA break sites, the regulation of repair factor expression, and the stabilisation of repair intermediates. DDR can also be communicated intercellularly via exosomes, leading to bystander responses in healthy neighbour cells to generate a population-wide response to damage. Many microRNA species have been directly implicated in the propagation of bystander DNA damage, autophagy, and radioresistance, which may prove significant for enhancing cancer treatment via radiotherapy. Here, we review recent developments centred around ncRNA and their contributions to intracellular and intercellular DDR mechanisms.
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Affiliation(s)
| | - Monika Gullerova
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK;
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18
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Lee D. miR-769-5p is associated with prostate cancer recurrence and modulates proliferation and apoptosis of cancer cells. Exp Ther Med 2021; 21:335. [PMID: 33732308 PMCID: PMC7903391 DOI: 10.3892/etm.2021.9766] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 12/15/2020] [Indexed: 12/14/2022] Open
Abstract
MicroRNAs (miRs) are relevant in biological processes, including human prostate cancer. In the present study, the role of miR-769-5p and its targets in prostate cancer were explored. Publicly available data on expression of genes, miRs and disease-free survival of patients with prostate cancer were analyzed along with RNAseq of transfected cell lines. miR-769-5p expression was inversely associated with patient survival and in vitro assays indicated that its inhibition reduced the proliferation and increased apoptosis of prostate cancer cells. miR-769-5p was revealed to target Rho GTPase activating protein 10 (ARHGAP10) and increased expression of ARHGAP10 in tumors was determined to be associated with a favorable prognosis regarding disease-free survival. Of note, ARHGAP10 is a purported tumor suppressor in ovarian cancer, where it inhibits cell division cycle 42 (CDC42) activity and increases apoptosis. Similar effects were observed in prostate cancer cells, where miR-769-5p inhibition increased ARHGAP10 and led to reduced CDC42 activity. Furthermore, miR-769-5p inhibition increased apoptosis, which was partly reversed by additional knockdown of ARHGAP10. These results suggested that miR-769-5p is an oncogene targeting ARHGAP10, which in turn is a candidate tumor suppressor in prostate cancer.
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Affiliation(s)
- Daniel Lee
- Medical Oncology Service and The Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
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19
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Yu L, Luan W, Feng Z, Jia J, Wu Z, Wang M, Li F, Li Z. Long non-coding RNA HAND2-AS1 inhibits gastric cancer progression by suppressing TCEAL7 expression via targeting miR-769-5p. Dig Liver Dis 2021; 53:238-244. [PMID: 32952069 DOI: 10.1016/j.dld.2020.08.045] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 08/06/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023]
Abstract
Increasing evidence showed that Heart and Neural Crest Derivatives Expressed 2 antisense RNA 1 (HAND2-AS1) was involved in the progression of several cancers, but its expression and function in gastric cancer (GC) was rarely reported. HAND2-AS1 expression in GC tissues and cells was detected at first. Cell function assays were performed to investigate the biological roles of HAND2-AS1 in GC cells. Moreover, the genes regulated by HAND2-AS1 in GC were investigated. Downregulation of HAND2-AS1 was found in GC tissues and cell lines. HAND2-AS1 overexpression inhibited GC cell proliferation, invasion, and arrested cell cycle at G0/G1 phase, whereas HADN2-AS1 knockdown significantly promoted cell proliferation and invasion. Bioinformatic analysis showed there is a potential HADN2-AS1/microRNA-769-5p (miR-769-5p)/transcription elongation factor A like 7 (TCEAL7) axis in GC. Luciferase activity reporter system was used to confirm this link. Taken together, our study showed that HAND2-AS1 exerts its tumor suppressive role in GC via regulating miR-769-5p/TCEAL7.
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Affiliation(s)
- Lan Yu
- Clinical Medical Research Center, and Department of Oncology, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, PR China.
| | - Wei Luan
- Department of Oncology, Inner Mongolia People's Hospital, Hohhot 010017, PR China
| | - Zongqi Feng
- Clinical Medical Research Center, and Department of Oncology, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, PR China
| | - Jianchao Jia
- Clinical Medical Research Center, and Department of Oncology, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, PR China
| | - Zhouying Wu
- Clinical Medical Research Center, and Department of Oncology, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, PR China
| | - Min Wang
- Clinical Medical Research Center, and Department of Oncology, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, PR China
| | - Feng Li
- Clinical Medical Research Center, and Department of Oncology, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, PR China
| | - Zhiying Li
- Clinical Medical Research Center, and Department of Oncology, Inner Mongolia People's Hospital, No. 20 Zhaowuda Road, Saihan District, Hohhot 010017, PR China
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20
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Knockdown of MALAT1 Inhibits the Progression of Chronic Periodontitis via Targeting miR-769-5p/HIF3A Axis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:8899863. [PMID: 33604388 PMCID: PMC7870306 DOI: 10.1155/2021/8899863] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 12/10/2020] [Accepted: 12/26/2020] [Indexed: 01/11/2023]
Abstract
Purpose Chronic periodontitis (CP) is a long-lasting inflammatory disease that seriously affects oral health. This study is aimed at investigating the regulatory mechanism of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in CP. Methods Primary human periodontal ligament cells (PDLCs) were treated with P. gingivalis lipopolysaccharide (LPS) to establish a CP model. Quantitative real-time PCR (qRT-PCR) was used to measure the expression of MALAT1 and miR-769-5p in gingival tissues of patients with CP and LPS-treated PDLCs. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines. The protein levels of caspase-3, Bax, Bcl-2, and hypoxia-inducible factor (HIF) 3A were determined by western blot assay. Dual-luciferase reporter (DLR) assay was applied to validate the target relationships between miR-769-5p and MALAT1/HIF3A. Results The expression of MALAT1 and HIF3A was enhanced, and the expression of miR-769-5p was reduced in gingival tissues of patients with CP and LPS-treated PDLCs. MALAT1 knockdown promoted cell viability and inhibited inflammation and cell apoptosis in LPS-treated PDLCs. MALAT1 targeted miR-769-5p and negatively regulated miR-769-5p expression. miR-769-5p overexpression promoted cell viability and inhibited inflammation and cell apoptosis in LPS-treated PDLCs. Besides, miR-769-5p targeted HIF3A and negatively modulated HIF3A expression. Both miR-769-5p inhibition and HIF3A overexpression reversed the inhibitory effects of MALAT1 silencing on LPS-induced PDLC injury in vitro. Conclusion MALAT1 knockdown attenuated LPS-induced PDLC injury via regulating the miR-769-5p/HIF3A axis, which may supply a new target for CP treatment.
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Lu X, Xu C, Xu Z, Lu C, Yang R, Zhang F, Zhang G. Piperlongumine inhibits the growth of non-small cell lung cancer cells via the miR-34b-3p/TGFBR1 pathway. BMC Complement Med Ther 2021; 21:15. [PMID: 33413277 PMCID: PMC7791704 DOI: 10.1186/s12906-020-03123-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 10/21/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Non-small cell lung cancer is a common type of lung cancer. Piperlongumine (PL), which is extracted from the roots of piperaceae plant, long pepper, and peppercorn, is an alkaloid amide that inhibits tumor growth and metastasis. However, whether it affects lung cancer cells remains unclear. METHODS We assessed the effects of PL on the proliferation and apoptosis of A549 and H1299 NSCLC cell lines. RESULTS PL was mildly toxic to normal human bronchial epithelial cells and significantly suppressed growth and facilitated apoptosis of A549 and H1299 cells. It also upregulated microRNA (miR)-34b-3p and downregulated the transforming growth factor beta type I receptor (TGFBR1). The dual-luciferase reporter assay showed that TGFBR1 is a target gene of miR-34b-3p. Silencing of miR-34b-3p or overexpression of TGFBR1 partially attenuated the effects of PL on A549 and H1299 cells. CONCLUSIONS PL inhibits proliferation and induces apoptosis of A549 and H1299 cells by upregulating miR-34b-3p and modulating TGFBR1 signaling pathway.
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Affiliation(s)
- Xinhua Lu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China
| | - Chenyang Xu
- Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Zhengzhou, 450015, China
| | - Zhexuan Xu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China
| | - Chunya Lu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China
| | - Rui Yang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China
| | - Furui Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China
| | - Guojun Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China.
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22
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Wang K, Zhang FL, Jia W. Glutathione S‑transferase ω 1 promotes the proliferation, migration and invasion, and inhibits the apoptosis of non‑small cell lung cancer cells, via the JAK/STAT3 signaling pathway. Mol Med Rep 2021; 23:71. [PMID: 33236161 PMCID: PMC7716429 DOI: 10.3892/mmr.2020.11709] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 10/21/2020] [Indexed: 12/25/2022] Open
Abstract
Glutathione S‑transferase ω 1 (GSTO1) expression levels have been discovered to be upregulated in various types of cancer. However, to the best of our knowledge, the role of GSTO1 in non‑small cell lung cancer (NSCLC) has not been investigated. The present study aimed to investigate the role of GSTO1 in NSCLC and to determine the potential molecular mechanism. GSTO1 expression levels in A549 cells were knocked down using short hairpin RNA and GSTO1 overexpression in H2122 cells was achieved using cDNA constructs. Reverse transcription‑quantitative PCR was used to analyze the mRNA expression levels of GSTO1. Cell proliferation was determined using a Cell Counting Kit‑8 assay, whereas cell migration and invasion were analyzed using Transwell assays. Flow cytometric analysis was performed to determine the levels of cell apoptosis. The expression levels of GSTO1, Bax, caspase 3, JAK and STAT3 were analyzed using western blotting. The results revealed that GSTO1 overexpression significantly promoted the proliferation, migration and invasion, and inhibited the apoptosis of H2122 cells, whereas the opposite trend was achieved in A549 cells with GSTO1 knockdown. GSTO1 overexpression also significantly increased the phosphorylation levels of JAK and STAT3, whereas the knockdown of GSTO1 promoted the opposite effects. In conclusion, the findings of the present study indicated that GSTO1 may serve as an oncogene in NSCLC. The results suggested that GSTO1 may have an important role in NSCLC by regulating the JAK/STAT3 signaling pathway. Therefore, inhibiting the expression levels of GSTO1 may represent a potential novel therapeutic strategy for NSCLC.
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Affiliation(s)
- Kai Wang
- Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin 300222, P.R. China
| | - Fu-Lian Zhang
- Integrated TCM and Western Medicine Department, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin 300134, P.R. China
| | - Wei Jia
- Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin 300222, P.R. China
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23
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Ni N, Ma W, Tao Y, Liu J, Hua H, Cheng J, Wang J, Zhou B, Luo D. Exosomal MiR-769-5p Exacerbates Ultraviolet-Induced Bystander Effect by Targeting TGFBR1. Front Physiol 2020; 11:603081. [PMID: 33329055 PMCID: PMC7719707 DOI: 10.3389/fphys.2020.603081] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 10/28/2020] [Indexed: 12/24/2022] Open
Abstract
Exosomal microRNAs have been investigated in bystander effect, but it is unclear whether microRNA works in ultraviolet radiation-induced bystander effects (UV-RIBEs) and what the underlying mechanism could be. Exosomes from ultraviolet (UV)-irradiated human skin fibroblasts (HSFs) were isolated and transferred to normal HSFs, followed by the detection of proliferation rate, oxidative damage level, and apoptosis rate. Exosomal miRNAs were evaluated and screened with miRNA sequencing and quantitative reverse transcriptase-polymerase chain reaction method. MiRNA shuttle and bystander photodamage reactions were observed after transfection of miR-769-5p. MiR-769-5p targeting gene transforming growth factor-β1 (TGFBR1), and TGFBR1 mRNA 3'-untranslated region (UTR) was assessed and identified by Western blotting and dual-luciferase reporter assay. Bystander effects were induced after being treated with isolated exosomes from UV-irradiated HSFs. Exosomal miR-769-5p expression was significantly upregulated. Human skin fibroblasts showed lower proliferation, increasing oxidative damage, and faster occurrence of apoptosis after transfection. Exosome-mediated transfer of miR-769-5p was observed. Upregulation of miR-769-5p induced bystander effects, whereas downregulation of miR-769-5p can suppress UV-RIBEs. In addition, miR-769-5p was found to downregulate TGFBR1 gene expression by directly targeting its 3'-UTR. Our results demonstrate that exosome-mediated miR-769-5p transfer could function as an intercellular messenger and exacerbate UV-RIBEs. MiR-769-5p inhibits the expression of TGFBR1 by targeting TGFBR1 mRNA 3'-UTR.
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Affiliation(s)
- Na Ni
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Weiwei Ma
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yanling Tao
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Juan Liu
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Hua
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiawei Cheng
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jie Wang
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bingrong Zhou
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dan Luo
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Liu R, Zhang Y, Ding Y, Zhang S, Pan L. Characteristics of TGFBR1-EGFR-CTNNB1-CDH1 Signaling Axis in Wnt-Regulated Invasion and Migration in Lung Cancer. Cell Transplant 2020; 29:963689720969167. [PMID: 33231090 PMCID: PMC7784602 DOI: 10.1177/0963689720969167] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
This study aimed to explore the characteristics of TGFBR1-epidermal growth factor receptor (EGFR)-CTNNB1-CDH1 axis in regulating the invasion and migration in lung cancer. Using the small interfering RNA technology, EGFR was silenced in H2170 and H1299 cells. Then, the colony formation, migration, and invasion abilities were detected using colony-forming assay and transwell assay. Moreover, the mRNA expression of smad2, smad3, CTNNB1, and CDH1, and the protein expression of TGFBR1, CDH1, and TCF were determined using the real-time polymerase chain reaction and western blotting. The results showed that silencing EGFR could significantly decrease the colony-forming ability in H2170 and H1299. Knocking down EGFR could significantly inhibit the invasion and migration ability of H2179 and H1299. Inhibiting the expression of EGFR could significantly decrease the expression of smad2, smad3, CDH1, and CTNNB1, with all P-values <0.05. In addition, silencing EGFR could markedly decrease the expression of TGFBR1 and CDH1 in H1299 and H2170, with all P-values <0.05. In conclusion, silencing EGFR could significantly regulate the progression of lung cancer via TGFBR1-EGFR-CTNNB1-CDH1 axis in Wnt signaling pathway.
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Affiliation(s)
- Rong Liu
- Department of Radiology, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Yusui Zhang
- Department of Radiology, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Yuan Ding
- Department of Radiology, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Shuai Zhang
- Department of Interventional Radiology, the Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, China
- Shuai Zhang, Department of Interventional Radiology, the Affiliated Cancer Hospital of Guizhou Medical University, No. 1 West Beijing Road, Guiyang 550004, China.
| | - Long Pan
- Department of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University, Shanghai, China
- Long Pan, Department of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University. No. 301 Middle Yan Chang Road, Shanghai 200072, China.
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25
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Zeng B, Chen T, Luo J, Xie M, Wei L, Xi Q, Sun J, Zhang Y. Exploration of Long Non-coding RNAs and Circular RNAs in Porcine Milk Exosomes. Front Genet 2020; 11:652. [PMID: 32714373 PMCID: PMC7343709 DOI: 10.3389/fgene.2020.00652] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 05/28/2020] [Indexed: 12/12/2022] Open
Abstract
RNA in milk exosomes can be absorbed in the mammalian intestinal tract and function in gene expression regulations. Our previous work demonstrated that porcine milk exosomes (PME) contain large amounts of miRNAs and mRNAs. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are of particular interest, given their key role in diverse biological processes of animals. However, the expression profiles and the potential functions of lncRNAs and circRNAs in PME are still unknown. In the present study, we isolated PME by ultracentrifugation and performed a comprehensive analysis of lncRNA and circRNA in PME by using RNA sequencing. As a result, 2,466 novel lncRNAs, 809 annotated lncRNAs, and 61 circRNAs were identified in PME. The lncRNAs shared similar characteristics with other mammals in terms of length, exon number, and open reading frames. However, lncRNAs showed a higher level compared with mRNAs. Eight lncRNAs and five circRNAs in PME were selected for PCR identification. A functional enrichment analysis on the target genes of lncRNAs indicated that these genes were involved in cellular macromolecule metabolic, RNA metabolic, and immune processes. The circRNAs host genes were enriched in nucleic acid binding and adherence junction. We also evaluated the potential interaction targets between miRNAs and PME lncRNAs or circRNAs, and the results showed that the PME lncRNAs and the circRNAs have a high density of miRNA target sites. The top 20 highly expressed lncRNAs were found to interact with the proliferation-related miRNAs, and the circRNAs potentially targeted many miRNAs that are associated with the intestinal barrier. This study is the first to provide a resource for lncRNA and circRNA research of porcine milk. Moreover, the potential interaction between lncRNA/circRNA and miRNA is revealed. The present study expands our knowledge of non-coding RNAs in milk, and additional research is necessary to confirm their exactly physiological functions.
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Affiliation(s)
- Bin Zeng
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Ting Chen
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Junyi Luo
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Meiying Xie
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Limin Wei
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Qianyun Xi
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jiajie Sun
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Yongliang Zhang
- Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
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Bai Q, Li L, Chen F, Zhu J, Cao L, Yang Y, Zhong F. Suppression of Circular RNA Hsa_circ_0109320 Attenuates Non-Small Cell Lung Cancer Progression via MiR-595/E2F7 Axis. Med Sci Monit 2020; 26:e921200. [PMID: 32508344 PMCID: PMC7297023 DOI: 10.12659/msm.921200] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background Circular RNAs (circRNAs) are frequently aberrantly expressed in non-small cell lung cancer (NSCLC) and are considered to exert a pivotal role in the occurrence and development of NSCLC via targeting and negatively regulating microRNAs (miRNAs). We aimed to investigate the role of hsa_circ_0109320 in the proliferation, invasion and apoptosis of NSCLC, and explore its underlying molecular mechanism. Material/Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the circ_0109320 and miR-595 expression in tissues or cells. Western blot analysis was conducted to examine the cleaved caspase-3, Bax, Bcl-2, and E2F7 protein expression. Transwell detection was used to evaluate the invasion level of NSCLC cell lines. Results The results of present study indicated that circ_0109320 expression in NSCLC patients was upregulated significantly in tumor tissues compared with tissues adjacent to carcinoma. Upregulated circ_0109320 level was significantly associated with TNM stages as well as lymph node metastasis of NSCLC. Moreover, downregulation of circ_0109320 attenuated proliferation and invasion while promoting apoptosis in NSCLC cells. We further confirmed that circ_0109320 could sponge miR-595 to upregulate E2F7 expression. Silencing of miR-595 or overexpression of E2F2 could partially reversed the inhibitory role of circ_0109320 knockdown in NSCLC cells. These data provided evidence that the suppression of circ_0109320 attenuates NSCLC cell proliferation and invasion and enhances apoptosis through the miR-595/E2F7 pathway. Conclusions Circ_0109320/miR-595/E2F2 axis may exert a pivotal role in the pathological mechanism of NSCLC progression, and it has potential application in the future treatment of NSCLC.
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Affiliation(s)
- Qiaohong Bai
- Department of Respiratory, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland)
| | - Li Li
- Department of Respiratory, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China (mainland)
| | - Futao Chen
- Department of Respiratory, The Second Hospital of LianYunGang, Lianyungang, Jiangsu, China (mainland)
| | - Jiang Zhu
- Department of Respiratory, The Second Hospital of LianYunGang, Lianyungang, Jiangsu, China (mainland)
| | - Lifeng Cao
- Department of Respiratory, The Second Hospital of LianYunGang, Lianyungang, Jiangsu, China (mainland)
| | - Yang Yang
- Department of Respiratory, The Second Hospital of LianYunGang, Lianyungang, Jiangsu, China (mainland)
| | - Fukuan Zhong
- Department of Respiratory, The Second Hospital of LianYunGang, Lianyungang, Jiangsu, China (mainland)
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27
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Dong Y, Wan G, Yan P, Qian C, Li F, Peng G. Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression. Aging (Albany NY) 2020; 12:7729-7746. [PMID: 32369777 PMCID: PMC7244063 DOI: 10.18632/aging.103075] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 03/24/2020] [Indexed: 12/19/2022]
Abstract
Long intergenic non–protein-coding RNA 324 (LINC00324) is abnormally expressed in multiple human cancer types and plays an important role in cancer initiation and progression. This study showed that LINC00324 was expressed at higher levels in retinoblastoma (RB) tumors and cell lines than in control samples. Increased LINC00324 expression closely correlated with the TNM stage, optic nerve invasion, and shorter overall survival among patients with RB. The knockdown of LINC00324 decreased RB cell proliferation, colony formation, migration, and invasion, and promoted apoptosis and cell cycle arrest in vitro as well as hindered tumor growth in vivo. With respect to the mechanism, LINC00324 acted as a competing endogenous RNA for microRNA-769-5p (miR-769-5p) in RB cells. The mRNA of signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-769-5p in RB cells. Rescue experiments indicated that restoration of STAT3 expression attenuated the tumor-suppressive actions of miR-769-5p in RB cells. Downregulation of miR-769-5p or restoration of STAT3 almost completely reversed the effects of LINC00324 knockdown on RB cells. Our findings describe a novel RB-related LINC00324–miR-769-5p–STAT3 axis that is implicated in the malignancy of RB in vitro and in vivo. This study may point to innovative therapeutic targets in RB.
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Affiliation(s)
- Yi Dong
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou 450052, Henan, China
| | - Guangming Wan
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou 450052, Henan, China
| | - Panshi Yan
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou 450052, Henan, China
| | - Cheng Qian
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou 450052, Henan, China
| | - Fuzhen Li
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou 450052, Henan, China
| | - Guanghua Peng
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450002, Henan, China
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28
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Zalewski DP, Ruszel KP, Stępniewski A, Gałkowski D, Bogucki J, Komsta Ł, Kołodziej P, Chmiel P, Zubilewicz T, Feldo M, Kocki J, Bogucka-Kocka A. Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease. J Clin Med 2020; 9:jcm9051251. [PMID: 32344947 PMCID: PMC7287878 DOI: 10.3390/jcm9051251] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/20/2020] [Accepted: 04/21/2020] [Indexed: 12/12/2022] Open
Abstract
Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.
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Affiliation(s)
- Daniel P. Zalewski
- Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland; (D.P.Z.); (P.K.); (P.C.)
| | - Karol P. Ruszel
- Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland; (K.P.R.); (J.B.); (J.K.)
| | - Andrzej Stępniewski
- Ecotech Complex Analytical and Programme Centre for Advanced Environmentally Friendly Technologies, University of Marie Curie-Skłodowska, 39 Głęboka St., 20-612 Lublin, Poland;
| | - Dariusz Gałkowski
- Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, New Brunswick, NJ 08903-0019, USA;
| | - Jacek Bogucki
- Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland; (K.P.R.); (J.B.); (J.K.)
| | - Łukasz Komsta
- Chair and Department of Medicinal Chemistry, Medical University of Lublin, 4 Jaczewskiego St., 20-090 Lublin, Poland;
| | - Przemysław Kołodziej
- Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland; (D.P.Z.); (P.K.); (P.C.)
| | - Paulina Chmiel
- Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland; (D.P.Z.); (P.K.); (P.C.)
| | - Tomasz Zubilewicz
- Chair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, Poland; (T.Z.); (M.F.)
| | - Marcin Feldo
- Chair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, Poland; (T.Z.); (M.F.)
| | - Janusz Kocki
- Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland; (K.P.R.); (J.B.); (J.K.)
| | - Anna Bogucka-Kocka
- Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland; (D.P.Z.); (P.K.); (P.C.)
- Correspondence: ; Tel.: +48-81-448-7232
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Li L, Wan K, Xiong L, Liang S, Tou F, Guo S. CircRNA hsa_circ_0087862 Acts as an Oncogene in Non-Small Cell Lung Cancer by Targeting miR-1253/RAB3D Axis. Onco Targets Ther 2020; 13:2873-2886. [PMID: 32308420 PMCID: PMC7138622 DOI: 10.2147/ott.s243533] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 03/09/2020] [Indexed: 12/14/2022] Open
Abstract
Purpose Circular RNAs (circRNAs) have been found to regulate several human tumors. The present study was to explore the mechanism of hsa_circ_0087862 in regulating non-small cell lung cancer (NSCLC). Methods Totally 102 NSCLC cases were enrolled. NCI-H1359 and A549 cells were transfected. Cells viability, apoptosis, migration and invasion were determined by CCK-8 assay, flow cytometry, scratch test and transwell experiment, respectively. Luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were performed. Xenograft tumor experiments were performed using nude mice. hsa_circ_0087862, miR-1253 and RAB3D expression in tissues/cells were detected by qRT-PCR. RAB3D and Ki67 protein expressions in cells/tissues were researched by Western blot and immunohistochemistry. Apoptosis of xenograft tumor tissue cells was detected using Tunel assay. Results hsa_circ_0087862 was significantly up-regulated in NSCLC patients, which was associated with poor prognosis (P < 0.05). hsa_circ_0087862 down-regulation prominently weakened NSCLC cells viability, migration, invasion and enhanced apoptosis (P < 0.01). hsa_circ_0087862 overexpression exhibited the opposite results in NSCLC cells. miR-1253 was sponged by hsa_circ_0087862. miR-1253 expression in NSCLC tissues was negatively correlated with hsa_circ_0087862 (P < 0.001). RAB3D expression in NSCLC was directly inhibited by miR-1253. miR-1253 down-regulation or RAB3D overexpression dramatically reversed NSCLC cells phenotype induced by hsa_circ_0087862 down-regulation. hsa_circ_0087862 down-regulation markedly inhibited tumor growth in vivo (P < 0.01). In xenograft tumor tissues, hsa_circ_0087862 down-regulation obviously decreased expression of RAB3D, Ki67 and increased apoptosis. Conclusion hsa_circ_0087862 acted as an oncogene in NSCLC by targeting miR-1253/RAB3D.
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Affiliation(s)
- Lin Li
- Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang 330029, People's Republic of China
| | - Ke Wan
- Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang 330029, People's Republic of China
| | - Linkai Xiong
- Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang 330029, People's Republic of China
| | - Shuang Liang
- Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang 330029, People's Republic of China
| | - Fangfang Tou
- Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang 330029, People's Republic of China
| | - Shanxian Guo
- Department of Thoracic Oncology, Jiangxi Cancer Hospital, Nanchang 330029, People's Republic of China
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A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5973082. [PMID: 32104700 PMCID: PMC7035545 DOI: 10.1155/2020/5973082] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 08/07/2019] [Accepted: 12/20/2019] [Indexed: 12/25/2022]
Abstract
Objective We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). Results With cut-off criteria of P < 0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan–Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. Conclusions Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.
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Chen Y, Zhang W, Kadier A, Zhang H, Yao X. MicroRNA-769-5p suppresses cell growth and migration via targeting NUSAP1 in bladder cancer. J Clin Lab Anal 2020; 34:e23193. [PMID: 31901150 PMCID: PMC7246360 DOI: 10.1002/jcla.23193] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 11/16/2019] [Accepted: 12/11/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Nucleolar and spindle-associated protein 1 (NUSAP1) has been identified to be strongly implicated in the carcinogenesis of cervical carcinoma, breast cancer, and liver cancer, and shows a high expression level in bladder cancer, indicating that NUSAP1 might be a potent target for cancer treatment. Using bioinformatics methods, we found that NUSAP1 was a putative target of miR-769-5p. Here, we aimed to explore whether miR-769-5p is involved in bladder cancer progression via targeting NUSAP1. METHODS MiR-769-5p expression patterns in bladder cancer tissues and cells were detected by RT-PCR. Kaplan-Meier was used to determine the clinical effects of miR-769-5p expression levels on the overall survival of bladder cancer patients. Bioinformatics methods were used to predict the binding sites between miR-769-5p and NUSAP1, which was verified by the luciferase gene reporter assay. CCK-8, flow cytometry, wound healing and transwell chamber experiments were performed to test cell growth, apoptosis, migration and invasion capacities. RESULTS miR-769-5p was lowly expressed in bladder cancer tissues and cells, which was closely associated with poor prognosis. Overexpression of miR-769-5p induced significant repressions in cell growth, migration, and invasion and caused an obvious increase in cell apoptosis, whereas these tendencies were reversed when NUSAP1 was upregulated. CONCLUSION This study demonstrates that miR-769-5p functions as a tumor suppressor in bladder cancer via targeting NUSAP1.
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Affiliation(s)
- Yifan Chen
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Wentao Zhang
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Aimaitiaji Kadier
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Haimin Zhang
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Xudong Yao
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
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Cheng K, Feng L, Yu S, Yu C, Chi N. MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1. Onco Targets Ther 2019; 12:11737-11750. [PMID: 32099382 PMCID: PMC6997441 DOI: 10.2147/ott.s218876] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 12/07/2019] [Indexed: 12/12/2022] Open
Abstract
Purpose MicroRNA-769-5p (miR-769) is aberrantly expressed and plays crucial roles in non-small cell lung cancer and melanoma. However, the expression pattern, biological role, and mechanisms of action of miR-769 in pancreatic ductal adenocarcinoma (PDAC) are yet to be fully elucidated. Therefore, we attempted to determine the potential regulatory function of miR-769 in PDAC progression and to explore the underlying mechanisms in detail. Methods In this study, reverse-transcription quantitative polymerase chain reaction was carried out to determine the expression profile of miR-769 in PDAC. A series of experiments, including a Cell Counting Kit-8 assay, flow-cytometric analysis, Transwell migration and invasion assays, and a xenograft animal model, were applied to test whether miR-769 affects the malignancy of PDAC. Results We found that miR-769 was significantly underexpressed in PDAC tissues and cell lines. The low miR-769 expression significantly correlated with the TNM stage and lymph node metastasis. Patients with PDAC harboring low miR-769 expression showed shorter overall survival than did the patients with high miR-769 expression. Forced upregulation of miR-769 suppressed PDAC cell proliferation, migration, and invasion in vitro; promoted apoptosis in vitro; and hindered tumor growth in vivo. Experiments on the mechanism identified ETS proto-oncogene 1 (ETS1) as a direct target gene of miR-769 in PDAC cells. Furthermore, ETS1 turned out to be upregulated in PDAC tissue samples, and the upregulation of ETS1 negatively correlated with miR-769 expression. Moreover, ETS1 knockdown simulated the tumor-suppressive effects of miR-769 overexpression on PDAC cells. Besides, ETS1 reintroduction attenuated the antitumor actions of miR-769 upregulation in PDAC cells. Conclusion Our findings indicate that miR-769 performs tumor-suppressive functions in PDAC by directly targeting ETS1, and this miRNA may represent a potential therapeutic target for the development of anticancer therapies.
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Affiliation(s)
- Kai Cheng
- Department of Gastroenterology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China
| | - Lan Feng
- Department of Infectious Diseases, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China
| | - Shuang Yu
- Department of Cardiovascular Medicine, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China
| | - Changhong Yu
- Department of Gastroenterology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China
| | - Nannan Chi
- Department of Gastroenterology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China
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Chang M, Yan P, Zhang B, Zhang G, Wang J, Ge H, Han N, Du C, Shi W, Tian Y. MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A. Onco Targets Ther 2019; 12:9177-9187. [PMID: 31807002 PMCID: PMC6842300 DOI: 10.2147/ott.s222836] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 10/18/2019] [Indexed: 12/24/2022] Open
Abstract
Background Accumulating evidence supports the involvement of microRNAs (miRNAs) in the progression of human cancers including glioma. Recently, miR-769-5p has been reported to play a tumor suppressive role in colorectal cancer and lung cancer, whereas it exerts an oncogenic role in melanoma. However, the role of miR-769-5p and its related mechanism are poorly elucidated. Methods The levels of miR-769-5p in glioma tissues and adjacent non-tumor tissues were detected by qRT-PCR. In addition, the effects of miR-769-5p on cell proliferation and apoptosis were evaluated by CCK-8, EdU, colony formation and flow cytometric assays, respectively. Meanwhile, the dual-luciferase reporter assay was used to investigate the interaction of miR-769-5p and lysine methyltransferase 2A (KMT2A) in glioma. Results We found that miR-769-5p expression was strongly upregulated in glioma tissues and cell lines. Glioma tissues with high World Health Organization (WHO) grades had obvious higher levels of miR-769-5p compared to samples with low WHO grades. Interestingly, glioma patients highly expressing miR-769-5p showed prominent poorer survivals. Knockdown of miR-769-5p significantly suppressed cell proliferation and resulted in apoptosis in glioma cells. Additionally, miR-769-5p silencing restrained in vivo growth of glioma cells in mice. Interestingly, KMT2A was identified to be a direct target of miR-769-5p in glioma cells. The expression of KMT2A mRNA was downregulated in glioma tissues and inversely correlated with miR-769-5p level. KMT2A overexpression inhibited cell proliferation and induced the apoptosis of A172 cells. Moreover, siRNA-mediated KMT2A silencing could partially abolish miR-769-5p knockdown-induced suppressive effects on A172 cells. Conclusion In summary, our findings suggest that targeting miR-769-5p/KMT2A axis may be a promising therapeutic target for glioma treatment.
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Affiliation(s)
- Mingze Chang
- Department of Neurology, Xi'an No. 3 Hospital, Xi'an 710021, People's Republic of China.,Department of Neurology, The Affiliated Hospital of Northwest University, Xi'an 710021, People's Republic of China
| | - Peng Yan
- The College of Life Sciences, Northwest University, Xi'an 710069, People's Republic of China
| | - Bei Zhang
- Department of Neurology, The First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, People's Republic of China
| | - Gejuan Zhang
- Department of Neurology, Xi'an No. 3 Hospital, Xi'an 710021, People's Republic of China
| | - Juanhong Wang
- Department of Pathology, Xi'an No.3 Hospital, Xi'an 710021, People's Republic of China.,Departments of Pathology, Xi'an Central Hospital, Xi'an 71000, People's Republic of China
| | - Hanming Ge
- Department of Neurology, Xi'an No. 3 Hospital, Xi'an 710021, People's Republic of China
| | - Nannan Han
- Department of Neurology, Xi'an No. 3 Hospital, Xi'an 710021, People's Republic of China
| | - Chengxue Du
- Department of Neurology, Xi'an No. 3 Hospital, Xi'an 710021, People's Republic of China
| | - Wenzhen Shi
- Department of Neurology, Xi'an No. 3 Hospital, Xi'an 710021, People's Republic of China
| | - Ye Tian
- Department of Neurology, The Affiliated Hospital of Northwest University, Xi'an 710021, People's Republic of China
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Li W, Yang F, Gao J, Tang Y, Wang J, Pan Y. Over-Expression of TRPC6 via CRISPR Based Synergistic Activation Mediator in BMSCs Ameliorates Brain Injury in a Rat Model of Cerebral Ischemia/Reperfusion. Neuroscience 2019; 415:147-160. [PMID: 31369718 DOI: 10.1016/j.neuroscience.2019.06.041] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Revised: 06/26/2019] [Accepted: 06/27/2019] [Indexed: 12/23/2022]
Abstract
Stroke is a major life-threatening and disabling disease with a restricted therapeutic approach. Bone marrow stromal cells (BMSCs) possess proliferative ability and a multi-directional differentiation potential, and secrete a range of trophic/growth factors that can protect neurons after cerebral ischemia/reperfusion. Transient receptor potential canonical (TRPC) is a family of non-selective channels permeable to Ca2+, with several functions including neuronal survival. Over-expression of TRPC6, a subtype of the TRPC family, was shown to protect neurons against cerebral ischemia/reperfusion injury. However, it remains unclear whether over-expression of TRPC6 in BMSCs can further reduce brain injury after ischemia/reperfusion. In the present study, we report that over-expression of TRPC6 via a CRISPR-based synergistic activation mediator in BMSCs provided a greater reduction of brain injury in a rat model of ischemia/reperfusion. Further, the improved neurofunctional outcomes were associated with increased TRPC6 and brain derived neurotrophic factor expression levels. Overall, these data suggest that TRPC6 over-expressing BMSCs may be a promising therapeutic agent for ischemic stroke.
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Affiliation(s)
- Wenbin Li
- Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China
| | - Fan Yang
- Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China
| | - Jinxing Gao
- Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China
| | - Yushi Tang
- Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China
| | - Jing Wang
- Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China
| | - Yujun Pan
- Department of Neurology, First Clinical College of Harbin Medical University, Room 501, Building 3, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, People's Republic of China.
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Xian Y, Wang L, Yao B, Yang W, Mo H, Zhang L, Tu K. MicroRNA-769-5p contributes to the proliferation, migration and invasion of hepatocellular carcinoma cells by attenuating RYBP. Biomed Pharmacother 2019; 118:109343. [PMID: 31545279 DOI: 10.1016/j.biopha.2019.109343] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/01/2019] [Accepted: 08/07/2019] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the commonest primary liver cancer with highly aggressive features. MicroRNAs (miRNAs) are demonstrated to play important roles in the tumorigenesis and progression of HCC. miR-769-5p is a recently identified cancer-associated miRNA. But, the expression level of miR-769-5p and its function in HCC are unexplored. In this study, we found that miR-769-5p expression was obviously increased in HCC samples compared to adjacent noncancerous liver tissues. Additionally, we revealed that miR-769-5p was over-expressed in HCC cells as compared with LO2 cells. Notably, HCC tissues from patients with tumor size ≥5 cm, venous infiltration and advanced tumor stages showed higher levels of miR-769-5p compared to those from corresponding controls. Interestingly, our data indicated that HCC patients highly expressing miR-769-5p had significant shorter survivals. Next, functional experiments verified that miR-769-5p knockdown markedly suppressed HCC cell proliferation, migration and invasion. Conversely, ectopic expression of miR-769-5p promoted these biological behaviors of Hep3B cells. Furthermore, depletion of miR-769-5p repressed the growth and metastasis of HCCLM3 cells in vivo. Importantly, miR-769-5p inversely modulated RING1 and YY1 binding protein (RYBP) by directly binding to 3' untranslated region (UTR) in HCC cells. The expression of RYBP mRNA was down-regulated in HCC tissues and negatively correlated with miR-769-5p level. RYBP overexpression remarkably inhibited the proliferation, migration and invasion of HCCLM3 cells. Accordingly, knockdown of RYBP partially abolished miR-769-5p silencing-induced tumor suppressive effects on HCCLM3 cells. In summary, our study revealed the up-regulated expression of miR-769-5p, which contributed to HCC progression possibly by targeting RYBP.
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Affiliation(s)
- Yao Xian
- Department of Nutrition, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
| | - Liang Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
| | - Bowen Yao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
| | - Wei Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
| | - Huanye Mo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China
| | - Lei Zhang
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi Province 710061, China.
| | - Kangsheng Tu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.
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Rafieenia F, Abbaszadegan MR, Poursheikhani A, Razavi SMS, Jebelli A, Molaei F, Aghaee‐Bakhtiari SH. In silico evidence of high frequency of miRNA‐related SNPs in Esophageal Squamous Cell Carcinoma. J Cell Physiol 2019; 235:966-978. [DOI: 10.1002/jcp.29012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Affiliation(s)
- Fatemeh Rafieenia
- Medical Genetics Research Center Mashhad University of Medical Sciences Mashhad Iran
- Student Research Committee Mashhad University of Medical Sciences Mashhad Iran
| | - Mohammad Reza Abbaszadegan
- Medical Genetics Research Center Mashhad University of Medical Sciences Mashhad Iran
- Immunology Research Center Mashhad University of Medical Sciences Mashhad Iran
| | - Arash Poursheikhani
- Medical Genetics Research Center Mashhad University of Medical Sciences Mashhad Iran
| | | | - Amir Jebelli
- Stem Cell and Regenerative Medicine Research Department Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad Branch Mashhad Iran
| | - Fatemeh Molaei
- Medical Genetics Research Center Mashhad University of Medical Sciences Mashhad Iran
| | - Seyed Hamid Aghaee‐Bakhtiari
- Bioinformatics Research Group Mashhad University of Medical Sciences Mashhad Iran
- Department of Medical Biotechnology, Faculty of Medicine Mashhad University of Medical Sciences Mashhad Iran
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Ion Channel Targeting with Antibodies and Antibody Fragments for Cancer Diagnosis. Antibodies (Basel) 2019; 8:antib8020033. [PMID: 31544839 PMCID: PMC6640718 DOI: 10.3390/antib8020033] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 05/17/2019] [Accepted: 05/20/2019] [Indexed: 12/12/2022] Open
Abstract
The antibody era has greatly impacted cancer management in recent decades. Indeed, antibodies are currently applied for both cancer diagnosis and therapy. For example, monoclonal antibodies are the main constituents of several in vitro diagnostics, which are applied at many levels of cancer diagnosis. Moreover, the great improvement provided by in vivo imaging, especially for early-stage cancer diagnosis, has traced the path for the development of a complete new class of antibodies, i.e., engineered antibody fragments. The latter embody the optimal characteristics (e.g., low renal retention, rapid clearance, and small size) which make them ideal for in vivo applications. Furthermore, the present review focuses on reviewing the main applications of antibodies and antibody fragments for solid cancer diagnosis, both in vitro and in vivo. Furthermore, we review the scientific evidence showing that ion channels represent an almost unexplored class of ideal targets for both in vitro and in vivo diagnostic purposes. In particular, we review the applications, in solid cancers, of monoclonal antibodies and engineered antibody fragments targeting the voltage-dependent ion channel Kv 11.1, also known as hERG1.
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Zhang L, Song X, Chen X, Wang Q, Zheng X, Wu C, Jiang J. Circular RNA CircCACTIN Promotes Gastric Cancer Progression by Sponging MiR-331-3p and Regulating TGFBR1 Expression. Int J Biol Sci 2019; 15:1091-1103. [PMID: 31182928 PMCID: PMC6535790 DOI: 10.7150/ijbs.31533] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 02/27/2019] [Indexed: 01/05/2023] Open
Abstract
Background: Circular RNAs (circRNAs) are a new class of RNAs that play a significant role in regulating gene expression and biological function. However, the expression profile and function of circRNAs in gastric cancer (GC) remain mostly uncertain. In the present study, we researched the expression profile of circRNAs in human GC tissues and explored the role of circCACTIN (hsa_circ_0092303). Methods: Circular RNA microarray assays were performed to detect circular RNA expression profiles of GC and circCACTIN was identified for further investigation. Quantitative real-time PCR was used to detect the expression of circCACTIN, miR-331-3p and TGFBR1 in GC specimens and cell lines. CircCACTIN was stably silenced and overexpressed in GC cells, and cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), as well as tumorigenesis in nude mice were performed to assess the effect of circCACTIN on GC. Results: CircCACTIN expression was obviously up-regulated in GC tissues and cell lines. Knockdown of circCACTIN inhibited GC cells proliferation, migration, invasion and EMT. Enforced-expression of circCACTIN promoted GC cells migration, invasion and EMT, but had no effect on GC cells proliferation. Moreover, in vivo experiments, circCACTIN up-regulation promoted GC tumor growth and EMT, and circCACTIN down-regulation inhibited GC tumor growth and EMT. Binding interactions were detected between circCACTIN and miR-331-3p, and between miR-331-3p and TGFBR1 by Dual-luciferase reporter assays. Mechanistically, we demonstrated that circCACTIN promoted gastric cancer progression by sponging miRNA-331-3p and regulating TGFBR1 mRNA expression. Conclusion: The circCACTIN/miR-331-3p/TGFBR1 axis affected the proliferation, migration, invasion and EMT of GC through the mechanism of competing endogenous RNAs (ceRNA). Furthermore, our results identified circCACTIN as a novel oncogenic circRNA in GC.
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Affiliation(s)
- Luo Zhang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Xing Song
- Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Xin Chen
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Qi Wang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Xiao Zheng
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Changping Wu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Jingting Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.,Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
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Photopharmacology and opto-chemogenetics of TRPC channels-some therapeutic visions. Pharmacol Ther 2019; 200:13-26. [PMID: 30974125 DOI: 10.1016/j.pharmthera.2019.04.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 03/27/2019] [Indexed: 12/28/2022]
Abstract
Non-selective cation conductances formed by transient receptor potential canonical (TRPC) proteins govern the function and fate of a wide range of human cell types. In the past decade, evidence has accumulated for a pivotal role of these channels in human diseases, raising substantial interest in their therapeutic targeting. As yet, an appreciable number of small molecules for block and modulation of recombinant TRPC conductances have been identified. However, groundbreaking progress in TRPC pharmacology towards therapeutic applications is lagging behind due to incomplete understanding of their molecular pharmacology and their exact role in disease. A major breakthrough that is expected to overcome these hurdles is the recent success in obtaining high-resolution structure information on TRPC channel complexes and the advent of TRP photopharmacology and optogenetics. Here, we summarize current concepts of enhancing the precision of therapeutic interference with TRPC signaling and TRPC-mediated pathological processes.
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Pethő Z, Najder K, Bulk E, Schwab A. Mechanosensitive ion channels push cancer progression. Cell Calcium 2019; 80:79-90. [PMID: 30991298 DOI: 10.1016/j.ceca.2019.03.007] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 03/26/2019] [Accepted: 03/26/2019] [Indexed: 02/07/2023]
Abstract
In many cases, the mechanical properties of a tumor are different from those of the host tissue. Mechanical cues regulate cancer development by affecting both tumor cells and their microenvironment, by altering cell migration, proliferation, extracellular matrix remodeling and metastatic spread. Cancer cells sense mechanical stimuli such as tissue stiffness, shear stress, tissue pressure of the extracellular space (outside-in mechanosensation). These mechanical cues are transduced into a cellular response (e. g. cell migration and proliferation; inside-in mechanotransduction) or to a response affecting the microenvironment (e. g. inducing a fibrosis or building up growth-induced pressure; inside-out mechanotransduction). These processes heavily rely on mechanosensitive membrane proteins, prominently ion channels. Mechanosensitive ion channels are involved in the Ca2+-signaling of the tumor and stroma cells, both directly, by mediating Ca2+ influx (e. g. Piezo and TRP channels), or indirectly, by maintaining the electrochemical gradient necessary for Ca2+ influx (e. g. K2P, KCa channels). This review aims to discuss the diverse roles of mechanosenstive ion channels in cancer progression, especially those involved in Ca2+-signaling, by pinpointing their functional relevance in tumor pathophysiology.
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Affiliation(s)
- Zoltán Pethő
- Institut für Physiologie II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
| | - Karolina Najder
- Institut für Physiologie II, Robert-Koch-Str. 27b, 48149 Münster, Germany
| | - Etmar Bulk
- Institut für Physiologie II, Robert-Koch-Str. 27b, 48149 Münster, Germany
| | - Albrecht Schwab
- Institut für Physiologie II, Robert-Koch-Str. 27b, 48149 Münster, Germany
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Cao L, Jin H, Zheng Y, Mao Y, Fu Z, Li X, Dong L. DANCR-mediated microRNA-665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway. Cancer Sci 2019; 110:913-925. [PMID: 30582654 PMCID: PMC6398927 DOI: 10.1111/cas.13921] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 12/11/2018] [Accepted: 12/18/2018] [Indexed: 12/23/2022] Open
Abstract
Emerging evidence has indicated that microRNAs (miRNAs) play an important role in cervical cancer (CC). However, the role of miRNA (miR)-665 in cervical cancer remains unclear. The aim of the present study was to investigate the potential functions of miR-665 in CC and to identify the underlying mechanisms of action. Herein, we show that miR-665 was downregulated in CC tissues and cell lines, which is negatively correlated with tumor size, distant metastasis, advanced TNM stage and poor prognosis. Functionally, miR-665 inhibited cell proliferation, migration and invasion and resistance of cisplatin for CC cells, as well as tumor growth. We validated that transforming growth factor beta receptor 1 (TGFBR1) was a direct target of miR-665 and mediated the ERK/SMAD pathway. In addition, we identified miR-665 as the competing endogenous RNA for long noncoding (lnc)-DANCR. These observations suggested that lnc-DANCR-mediated miR-665 downregulation regulates the malignant phenotype of CC cells by targeting TGFBR1 through the ERK/SMAD pathway, which may present a pathway for novel therapeutic stratagems for CC therapy.
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Affiliation(s)
- Liyan Cao
- Department of Radiation OncologyThe First Hospital of QinhuangdaoQinhuangdaoChina
| | - Haihong Jin
- Department of GynecologyThe First Hospital of QinhuangdaoQinhuangdaoChina
| | - Yue Zheng
- Department of GastroenterologyThe First Hospital of QinhuangdaoQinhuangdaoChina
| | - Yu Mao
- Department of Radiation OncologyThe First Hospital of QinhuangdaoQinhuangdaoChina
| | - Zhanzhao Fu
- Department of Radiation OncologyThe First Hospital of QinhuangdaoQinhuangdaoChina
| | - Xin Li
- Department of Radiation OncologyThe First Hospital of QinhuangdaoQinhuangdaoChina
| | - Lixin Dong
- Department of Radiation OncologyThe First Hospital of QinhuangdaoQinhuangdaoChina
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Ma G, Zhu J, Liu F, Yang Y. Long Noncoding RNA LINC00460 Promotes the Gefitinib Resistance of Nonsmall Cell Lung Cancer Through Epidermal Growth Factor Receptor by Sponging miR-769-5p. DNA Cell Biol 2019; 38:176-183. [PMID: 30601026 PMCID: PMC6383575 DOI: 10.1089/dna.2018.4462] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The vital roles of long noncoding RNAs (lncRNAs) in the nonsmall cell lung cancer (NSCLC) tumorigenesis are increasingly important. This work aims to investigate the role of lncRNA LINC00460 in the gefitinib resistance of NSCLC cells and discover its relevant mechanism. Our finding reveals that the expression of lncRNA LINC00460 is upregulated in the gefitinib-resistant NSCLC tissue and cells, and closely correlated with advanced tumor stage and clinical poor prognosis outcome. Gain and loss functional assays are performed in gefitinib-resistant NSCLC cells (A549/GR), stating that LINC00460 facilitates the 50% inhibitive concentration of gefitinib for NSCLC cells, multidrug-resistant-related proteins (P-gp, MRP1, and BCRP), as well as the invasion. In vivo, LINC00460 silencing represses the tumor growth. Bioinformatics prediction tools and luciferase analysis confirm that the upregulated LINC00460 sponged miR-769-5p in NSCLC cells; moreover, epidermal growth factor receptor (EGFR) is identified as a direct target gene of miR-769-5p. Verification experiments confirm that the restoration of EGFR could weaken the sensibility of NSCLC cells toward the gefitinib. In conclusion, our result demonstrates that LINC00460 plays a pivotal role in gefitinib resistance of NSCLC cells by targeting EGFR through sponging miR-769-5p. This finding might serve as a therapeutic target for NSCLC.
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Affiliation(s)
- Guodong Ma
- 1 Department of Chest Surgery, Nanjing Chest Hospital, Nanjing, China
| | - Jiping Zhu
- 2 Department of Pneumology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China
| | - Feng Liu
- 1 Department of Chest Surgery, Nanjing Chest Hospital, Nanjing, China
| | - Yan Yang
- 3 Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Han C, Song Y, Lian C. MiR-769 Inhibits Colorectal Cancer Cell Proliferation and Invasion by Targeting HEY1. Med Sci Monit 2018; 24:9232-9239. [PMID: 30565566 PMCID: PMC6320662 DOI: 10.12659/msm.911663] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 08/30/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) have been widely recognized as essential regulators in human cancers, including colorectal cancer (CRC). Whether miR-769 is implicated in CRC progression remains elusive. The present study aimed to determine the function of miR-769 in CRC. MATERIAL AND METHODS MiR-769 expression in CRC tissues and adjacent normal tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Kaplan-Meier curve analysis was utilized to determine the association between miR-769 expression and prognosis in CRC patients. The effects of miR-769 overexpression on CRC cell proliferation, cell cycle and invasion were analyzed using Cell Counting Kit-8 (CCK8), fluorescence activated cell sorting (FACS), and Transwell assays. Western blot was utilized to assess the effect of miR-769 on HEY1 expression. RESULTS MiR-769 expression was decreased in CRC tissues. MiR-769 level was negatively correlated with the prognosis of CRC patients. Additionally, miR-769 overexpression remarkably inhibited cell proliferation, arrested CRC cells in G0 stage, and reduced cellular invasion. As to the mechanism, HEY1 was a direct target of miR-769; HEY1 level was inversely correlated with that of miR-769 in CRC tissues. Finally, overexpression of HEY1 reversed the effects of miR-769 on cell proliferation and invasion in CRC. CONCLUSIONS Our findings demonstrated that miR-769 suppressed the proliferation and invasion of CRC cells through targeting HEY1, which implied that miR-769 might be a novel therapeutic target for CRC treatment.
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Wang L, Xu M, Lu P, Zhou F. microRNA-769 is downregulated in colorectal cancer and inhibits cancer progression by directly targeting cyclin-dependent kinase 1. Onco Targets Ther 2018; 11:9013-9025. [PMID: 30588014 PMCID: PMC6296200 DOI: 10.2147/ott.s183847] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND In recent years, microRNAs (miRNAs) have been reported to be aberrantly expressed in colorectal cancer (CRC). The deregulation of miRNAs is implicated in the formation and progression of CRC, and participates in the regulation of a wide range of biological behaviors. Considering the crucial role of miRNAs in CRC, miRNAs are thought to have significant promise in the diagnosis and therapy of patients with this malignancy. MATERIAL AND METHODS Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-769 expression in CRC tissues and cell lines. MTT assay and flow cytometry analysis were used to determine the effects of miR-769 upregulation in CRC cell proliferation and apoptosis, respectively. The influence of miR-769 overexpression in CRC cell migration and invasion was evaluated through migration and invasion assays. Notably, the possible mechanisms underlying the action of miR-769 in CRC cells were explored. RESULTS In the present study, miR-769 was frequently found to be poorly expressed in CRC tissues and cell lines. Functional assays showed that recovery of miR-769 expression suppressed CRC cell proliferation, migration, and invasion, increased cell apoptosis in vitro, and inhibited tumor growth in vivo. Cyclin-dependent kinase 1 (CDK1) was the direct target of miR-769 in CRC cells. CDK1 was overexpressed in CRC tissue samples and negatively correlated with miR-769 expression. In addition, CDK1 inhibition imitated the tumor suppressor activity of miR-769 in CRC cells, and restoration of CDK1 expression partially abolished the tumor-suppressing roles of miR-769 in malignant CRC cells. CONCLUSION The results of this study demonstrated that miR-769 was downregulated in CRC and directly targeted CDK1 to be implicated in the regulation of CRC cell proliferation, apoptosis, migration and invasion. Thus, the miR-769/CDK1 axis might be an effective therapeutic target for treating patients with CRC.
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Affiliation(s)
- Lei Wang
- Department of Clinical Laboratory, Shanghai Eighth People's Hospital, Xuhui Branch of Shanghai Sixth People's Hospital, Shanghai 200235, People's Republic of China,
| | - Minyi Xu
- Department of Clinical Laboratory, Shanghai Eighth People's Hospital, Xuhui Branch of Shanghai Sixth People's Hospital, Shanghai 200235, People's Republic of China,
| | - Pei Lu
- Department of Clinical Laboratory, Shanghai Eighth People's Hospital, Xuhui Branch of Shanghai Sixth People's Hospital, Shanghai 200235, People's Republic of China,
| | - Fangfang Zhou
- Department of Clinical Laboratory, Shanghai Eighth People's Hospital, Xuhui Branch of Shanghai Sixth People's Hospital, Shanghai 200235, People's Republic of China,
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Gao P, Wang H, Yu J, Zhang J, Yang Z, Liu M, Niu Y, Wei X, Wang W, Li H, Wang Y, Sun G. miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2. PLoS Genet 2018; 14:e1007790. [PMID: 30557355 PMCID: PMC6312350 DOI: 10.1371/journal.pgen.1007790] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 12/31/2018] [Accepted: 10/25/2018] [Indexed: 01/07/2023] Open
Abstract
Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.
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MESH Headings
- Aged
- Animals
- Biomarkers, Tumor/antagonists & inhibitors
- Biomarkers, Tumor/blood
- Biomarkers, Tumor/genetics
- Carcinoma, Non-Small-Cell Lung/genetics
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Non-Small-Cell Lung/therapy
- Cell Cycle/genetics
- Cell Line, Tumor
- Cell Movement/genetics
- Cell Proliferation/genetics
- Cyclins/antagonists & inhibitors
- Cyclins/genetics
- Down-Regulation
- Female
- Gene Knockdown Techniques
- Humans
- Lung Neoplasms/genetics
- Lung Neoplasms/pathology
- Lung Neoplasms/therapy
- Male
- Mice
- Mice, Nude
- Middle Aged
- Neoplasm Invasiveness/genetics
- Neoplasm Invasiveness/prevention & control
- Neoplasm Metastasis
- Prognosis
- RNA, Small Nucleolar/antagonists & inhibitors
- RNA, Small Nucleolar/blood
- RNA, Small Nucleolar/genetics
- Receptor, Transforming Growth Factor-beta Type I/antagonists & inhibitors
- Receptor, Transforming Growth Factor-beta Type I/genetics
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Affiliation(s)
- Peng Gao
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Huan Wang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Jiarui Yu
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Jie Zhang
- Department of pathology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Zhao Yang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Meiyue Liu
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Yi Niu
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Xiaomei Wei
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Wei Wang
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Hongmin Li
- Department of pathology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
| | - Yadi Wang
- Department of Radiation Oncology, PLA Army General Hospital, Beijing, China
| | - Guogui Sun
- Department of Radiation Oncology, North China University of Science and Technology Affiliated People’s Hospital, Tangshan, China
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Ramirez GA, Coletto LA, Bozzolo EP, Citterio L, Delli Carpini S, Zagato L, Rovere-Querini P, Lanzani C, Manunta P, Manfredi AA, Sciorati C. The TRPC6 intronic polymorphism, associated with the risk of neurological disorders in systemic lupus erythematous, influences immune cell function. J Neuroimmunol 2018; 325:43-53. [PMID: 30384327 DOI: 10.1016/j.jneuroim.2018.10.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Revised: 10/02/2018] [Accepted: 10/21/2018] [Indexed: 12/12/2022]
Abstract
Patients with systemic lupus erythematosus (SLE) carrying a TT genotype for the rs7925662 single nucleotide polymorphism (SNP) in the transient receptor potential canonical channel 6 (TRPC6) gene are more likely to develop neuropsychiatric manifestations (NPSLE). We functionally characterised the effects of TRPC6 on peripheral blood mononuclear cells from 18 patients with SLE and 8 healthy controls with a known genotype. TRPC6 influenced calcium currents, apoptosis rates and cytokine secretion in a disease- and genotype-dependent manner. Cells from TT patients with NPSLE were more dependent on TRPC6 for the generation of calcium currents.
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Affiliation(s)
- Giuseppe A Ramirez
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy
| | | | - Enrica P Bozzolo
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy
| | - Lorena Citterio
- Unit of Nephrology, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy
| | - Simona Delli Carpini
- Unit of Nephrology, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy
| | - Laura Zagato
- Unit of Nephrology, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy
| | - Patrizia Rovere-Querini
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy; Division of Immunology, Transplantation and Infectious Disease, San Raffaele Hospital & Scientific Institute Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy
| | - Chiara Lanzani
- Unit of Nephrology, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy
| | - Paolo Manunta
- Unit of Nephrology, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy
| | - Angelo A Manfredi
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital & Scientific Institute, Milan, Italy; Division of Immunology, Transplantation and Infectious Disease, San Raffaele Hospital & Scientific Institute Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy
| | - Clara Sciorati
- Division of Immunology, Transplantation and Infectious Disease, San Raffaele Hospital & Scientific Institute Milan, Italy.
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Han X, Liu CF, Gao N, Zhao J, Xu J. Kaempferol suppresses proliferation but increases apoptosis and autophagy by up-regulating microRNA-340 in human lung cancer cells. Biomed Pharmacother 2018; 108:809-816. [PMID: 30253373 DOI: 10.1016/j.biopha.2018.09.087] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 08/16/2018] [Accepted: 09/15/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Lung cancer is a leading cause of cancer-related deaths worldwide with unsatisfied prognosis. Kaempferol is a dietary flavonoid that inhibits tumorgenesis, and we aimed to uncover the underlying mechanism of kaempferol in lung cancer cells. METHODS A549 cells were stimulated with kaempferol, and then cell proliferation, apoptosis, autophagy and expression of miR-340 were assessed. Subsequently, effects of kaempferol on protein expression of phosphatase with tensin homology (PTEN) and key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT pathways were detected by Western blot analysis. Moreover, the effects of miR-340 inhibition on kaempferol-induced alterations in A549 cells were also studied. RESULTS Cell viability, proliferation and cyclinD1 expression level in A549 cells were all reduced by kaempferol. Conversely, cell apoptosis and autophagy were promoted by kaempferol. We found autophagy promoted apoptosis in kaempferol-treated A549 cells. Then, expression of miR-340 was identified to be up-regulated by kaempferol treatment. After treatments with kaempferol, PTEN level was elevated and levels of p-PI3K and p-AKT were decreased. Moreover, the alterations induced by kaempferol were abrogated by miR-340 inhibition. CONCLUSION Kaempferol inhibited proliferation but induced apoptosis and autophagy in A549 cells. Additionally, kaempferol might function through up-regulating miR-340, along with up-regulation of PTEN and inactivation of the PI3K/AKT pathway.
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Affiliation(s)
- Xue Han
- Department of Respiratory Medicine, Dalian Municipal Central Hospital, Dalian, 116033, China
| | - Chun-Fang Liu
- Department of Respiratory Medicine, Dalian Municipal Central Hospital, Dalian, 116033, China
| | - Na Gao
- Department of Respiratory Medicine, Dalian Municipal Central Hospital, Dalian, 116033, China
| | - Jing Zhao
- Department of Respiratory Medicine, Dalian Municipal Central Hospital, Dalian, 116033, China
| | - Jian Xu
- Department of Respiratory Medicine, Dalian Municipal Central Hospital, Dalian, 116033, China.
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Xu H, Wen Q. miR‑3120‑5p acts as a diagnostic biomarker in non‑small cell lung cancer and promotes cancer cell proliferation and invasion by targeting KLF4. Mol Med Rep 2018; 18:4621-4628. [PMID: 30221715 DOI: 10.3892/mmr.2018.9454] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 08/09/2018] [Indexed: 11/06/2022] Open
Abstract
Accumulating evidence indicates that microRNAs (miRs) are important regulators in a number of types of human cancer, including non‑small cell lung cancer (NSCLC). The function of miR‑3120‑5p in NSCLC remains unclear. In the present study, it was demonstrated that miR‑3120‑5p was significantly upregulated in NSCLC tissues. Additionally, miR‑3120‑5p expression level was positively associated with NSCLC metastasis and tumor, node and metastasis stage. Furthermore, it was demonstrated that miR‑3120‑5p exhibited potential as an indicator of NSCLC for use in diagnosis. Through functional experiments, it was demonstrated that overexpression of miR‑3120‑5p promoted the proliferation, colony formation and invasion of NSCLC cells. miR‑3120‑5p overexpression significantly promoted cell cycle progression. Mechanistically, it was demonstrated that Krueppel‑like factor 4 (KLF4) was a target of miR‑3120‑5p in NSCLC cells. Overexpression of miR‑3120‑5p repressed the expression of KLF4 in A549 and H460 cells. Furthermore, it was demonstrated that KLF4 was downregulated in NSCLC tissues and cell lines. Overexpression of KLF4 significantly reversed the effects of miR‑3120‑5p on NSCLC cell proliferation and invasion. In conclusion, the present study demonstrated that miR‑3120‑5p promoted NSCLC progression by directly targeting KLF4.
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Affiliation(s)
- Hongwei Xu
- Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Quan Wen
- General Internal Medicine Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
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Li Z, Lin C, Zhao L, Zhou L, Pan X, Quan J, Peng X, Li W, Li H, Xu J, Xu W, Guan X, Chen Y, Lai Y. Oncogene miR-187-5p is associated with cellular proliferation, migration, invasion, apoptosis and an increased risk of recurrence in bladder cancer. Biomed Pharmacother 2018; 105:461-469. [PMID: 29883941 DOI: 10.1016/j.biopha.2018.05.122] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 05/21/2018] [Accepted: 05/23/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Bladder cancer, the ninth-most-common malignancy worldwide with an estimated 356,000 new cases and 145,000 deaths annually, has a propensity to relapse, requiring lifelong monitoring after diagnosis. 75% patients diagnosed with BC are non-muscle invasive BC and over 50% of them experience recurrences within 6-12 years of initial diagnosis. miRNA are small, noncoding RNA and shown to be oncogenes or anti-oncogenes in bladder cancer, contributing to numerous BC cell processes, including cell proliferation, differentiation, migration and apoptosis. METHODS RT-qPCR were performed to detect the expression of miR-187-5p in tissues and cell lines, After which, clinicopathological variables and the prognostic value of altered miR-187-5p expression in BC was analyzed with the 48 formalin-fixed paraffin-embedded BC samples. Moreover, Cell functional assays (wound healing assay, CCK-8 assay, transwell assay and flow cytometry assay) were performed to explore the relationship between miR-187-5p expression and cell proliferation, migration, invasion and apoptosis in BC. RESULTS Up-regulation of miR-187-5p was observed in BC tissues and BC cell lines. Cox proportional hazard regression analysis demonstrated that the patients with low expression of miR-187-5p experience lower risks of recurrence in the univariate and multivariate analysis. The Kaplan-Meier recurrence-free curves suggested that the patients with low expression of miR-187-5p experience lower risks of recurrence. Up-regulation of miR-187-5p promotes cell proliferation and mobility and inhibits the apoptosis of 5637 and UM-UC-3 cell, while down-regulation of miR-187-5p reverses these effects. CONCLUSIONS The results of our study demonstrated that oncogene miR-187-5p is associated with cellular proliferation, migration, invasion, apoptosis and an increased risk of recurrence in bladder cancer.
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Affiliation(s)
- Zuwei Li
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; Department of Urology, Shantou University Medical College, Shantou, Guangdong 515041, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Canbin Lin
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; Department of Urology, Shantou University Medical College, Shantou, Guangdong 515041, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Liwen Zhao
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Liang Zhou
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Xiang Pan
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Jing Quan
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Xiqi Peng
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; Department of Urology, Shantou University Medical College, Shantou, Guangdong 515041, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Weiqing Li
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; Department of Urology, Shantou University Medical College, Shantou, Guangdong 515041, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Hang Li
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China
| | - Jinling Xu
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Weijie Xu
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Xin Guan
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China
| | - Yun Chen
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China.
| | - Yongqing Lai
- Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong 518036, PR China.
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Zhang H, Lu Y, Wang S, Sheng X, Zhang S. MicroRNA-152 Acts as a Tumor Suppressor MicroRNA by Inhibiting Krüppel-Like Factor 5 in Human Cervical Cancer. Oncol Res 2018; 27:335-340. [PMID: 30131089 PMCID: PMC7848453 DOI: 10.3727/096504018x15252202178408] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Aberrant expression of microRNA-152 (miR-152) is frequently observed in human cancers including ovarian cancer, breast cancer, prostate cancer, and gastric cancer. However, its expression and functional role in cervical cancer (CC) are poorly understood. Also, the association between miR-152 and Krüppel-like factor 5 (KLF5) expression in CC remains unclear. In this study, analyzing the expression of miR-152 by quantitative real-time PCR (qRT-PCR) revealed it was sharply reduced in CC tissues and cell lines. In addition, the negative correlation of miR-152 expression and KLF5 expression was observed. The dual-luciferase reporter assay validated that KLF5 was a target of miR-152. In vitro functional assays revealed that miR-152 could inhibit cell proliferation and cell cycle progression through regulating the expression of KLF5. Taken together, our study suggested that miR-152 functions as a tumor suppressor in CC, and the miR-152/KLF5 axis may provide novel therapeutic targets for CC treatment.
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Affiliation(s)
- Haiyan Zhang
- Department of Gynecology, Affiliated Qilu Hospital of Shandong University, Lixia District, Jinan, Shandong, P.R. China
| | - Yanxia Lu
- Department of Gynecology Ward-3, Linyi People's Hospital, Linyi, Hedong District, Linyi, Shandong, P.R. China
| | - Surong Wang
- Department of Gynecology Ward-3, Linyi People's Hospital, Linyi, Hedong District, Linyi, Shandong, P.R. China
| | - Xiugui Sheng
- Department of Gynecology, Cancer Hospital Chinese Academy of Medical Sciences, Chaoyang District, Beijing, P.R. China
| | - Shiqian Zhang
- Department of Gynecology, Affiliated Qilu Hospital of Shandong University, Lixia District, Jinan, Shandong, P.R. China
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