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Shamaeizadeh N, Mirian M. MicroRNA-219 in the central nervous system: a potential theranostic approach. Res Pharm Sci 2024; 19:634-655. [PMID: 39911893 PMCID: PMC11792714 DOI: 10.4103/rps.rps_163_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 01/16/2024] [Accepted: 04/02/2024] [Indexed: 02/07/2025] Open
Abstract
Despite the recent therapeutic advances in neurological disorders, curative therapy remains a serious challenge in many cases. Even though recent years have witnessed the development of gene therapy from among the different therapeutic approaches affecting pathophysiological mechanisms, intriguing aspects exist regarding the effectiveness, safety, and mechanism of action of gene therapies. Micro ribonucleic acid (microRNA-miRNA), as a fundamental gene regulator, regulates messenger ribonucleic acid (mRNA) by directly binding through the 3'-untranslated region (3'-UTR). MicroRNA-219 is a specific brain-enriched miRNA associated with neurodevelopmental disorders that play crucial roles in the differentiation of oligodendrocyte progenitorcells, promotion of oligodendrocyte maturation, remyelination, and cognitive functions to the extent that it can be considered a potential therapeutic option for demyelination in multiple sclerosis and spinal cord injury and reverse chronic inflammation pains. Additionally, miR-219 regulates the circadian clock, influencing the duration of the circadian clock period. This regulation can impact mood stability and is associated with phase fluctuations in bipolar patients. Furthermore, miR-219 also plays a role in modulating tau toxicity, which is relevant to the pathophysiology of Alzheimer's disease and schizophrenia. Finally, it reportedly has protective effects against seizures and Parkinson's disease, as well as neoplasms, by inhibiting proliferation, suppressing invasion, and inducing cell death in tumor cells. Exploring the miR-219 molecular pathways and their therapeutic effects on central nervous system disorders and the mechanisms involved, the present review study aims to illustrate how this information may change the future of gene therapy.
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Affiliation(s)
- Nahal Shamaeizadeh
- Department of Pharmaceutics and Novel Drug Delivery Systems Research Centre, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Mina Mirian
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
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2
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Song G, Yu X, Shi H, Sun B, Amateau S. miRNAs in HCC, pathogenesis, and targets. Hepatology 2024:01515467-990000000-01097. [PMID: 39626210 PMCID: PMC12119976 DOI: 10.1097/hep.0000000000001177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 11/22/2024] [Indexed: 12/21/2024]
Abstract
Liver cancer is the third leading cause of cancer-related mortality worldwide. HCC, the most common type of primary liver cancer, is driven by complex genetic, epigenetic, and environmental factors. MicroRNAs, a class of naturally occurring small noncoding RNAs, play crucial roles in HCC by simultaneously modulating the expression of multiple genes in a fine-tuning manner. Significant progress has been made in understanding how miRNAs influence key oncogenic pathways, including cell proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT), as well as their role in modulating the immune microenvironment in HCC. Due to the unexpected stability of miRNAs in the blood and fixed HCC tumors, recent advancements also highlight their potential as noninvasive diagnostic tools. Restoring or inhibiting specific miRNAs has offered promising strategies for targeted HCC treatment by suppressing malignant hepatocyte growth and enhancing antitumor immunity. In this comprehensive review, we consolidate previous research and provide the latest insights into how miRNAs regulate HCC and their therapeutic and diagnostic potential. We delve into the dysregulation of miRNA biogenesis in HCC, the roles of miRNAs in the proliferation and apoptosis of malignant hepatocytes, angiogenesis and metastasis of HCC, the immune microenvironment in HCC, and drug resistance. We also discuss the therapeutic and diagnostic potential of miRNAs and delivery approaches of miRNA drugs to overcome the limitations of current HCC treatment options. By thoroughly summarizing the roles of miRNAs in HCC, our goal is to advance the development of effective therapeutic drugs with minimal adverse effects and to establish precise tools for early diagnosis of HCC.
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Affiliation(s)
- Guisheng Song
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
- Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA
| | - Xiaofan Yu
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Hongtao Shi
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
- Department of Cardiology, the First Hospital of Shanxi Medical University, Taiyuan City, China
| | - Bo Sun
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Stuart Amateau
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
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3
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Toro AU, Shukla SK, Bansal P. Emerging role of MicroRNA-Based theranostics in Hepatocellular Carcinoma. Mol Biol Rep 2023; 50:7681-7691. [PMID: 37418086 DOI: 10.1007/s11033-023-08586-z] [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: 01/26/2023] [Accepted: 06/12/2023] [Indexed: 07/08/2023]
Abstract
Hepatocellular carcinoma (HCC), with its high mortality and short survival rate, continues to be one of the deadliest malignancies despite relentless efforts and several technological advances. The poor prognosis of HCC and the few available treatments are to blame for the low survival rate, which emphasizes the importance of creating new, effective diagnostic markers and innovative therapy strategies. In-depth research is being done on the potent biomarker miRNAs, a special class of non-coding RNA and has shown encouraging results in the early identification and treatment of HCC in order to find more viable and successful therapeutics for the disease. It is beyond dispute that miRNAs control cell differentiation, proliferation, and survival and, depending on the genes they target, can either promote tumorigenesis or suppress it. Given the vital role miRNAs play in the biological system and their potential to serve as ground-breaking treatments for HCC, more study is required to fully examine their theranostic potential.
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Affiliation(s)
- Abdulhakim Umar Toro
- Department of Biomedical Engineering, Shobhit institute of Engineering and Technology (Deemed to-be-University), Modipuram, Meerut, 250110, India
| | - Sudheesh K Shukla
- Department of Biomedical Engineering, Shobhit institute of Engineering and Technology (Deemed to-be-University), Modipuram, Meerut, 250110, India.
| | - Parveen Bansal
- University Centre of Excellence in Research, Baba Farid University of Health Sciences, Faridkot, 151203, India.
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Yan H, Ma X, Mi Z, He Z, Rong P. Extracellular Polysaccharide from Rhizopus nigricans Inhibits Hepatocellular Carcinoma via miR-494-3p/TRIM36 Axis and Cyclin E Ubiquitination. J Clin Transl Hepatol 2022; 10:608-619. [PMID: 36062277 PMCID: PMC9396321 DOI: 10.14218/jcth.2021.00301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/11/2021] [Accepted: 10/27/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS This study was designed to uncover the mechanism for extracellular polysaccharide (EPS1-1)-mediated effects on hepatocellular carcinoma (HCC) development. METHODS HCC cells were treated with EPS1-1, miR-494-3p mimic, sh-TRIM36, and pcDNA3.1-TRIM36. The levels of miR-494-3p and TRIM36 were measured in normal hepatocytes, THLE-2, and HepG2 and HuH7HCC cell lines, along with the protein expression of cyclin D/E and p21. The proliferation, cell cycle, and apoptosis of HCC cells were assayed. The interactions between miR-494-3p and TRIM36, and between TRIM36 and cyclin E were assessed. Finally, the expression and localization of TRIM36 and cyclin E were monitored, and tumor apoptosis was detected, in tumor xenograft model. RESULTS EPS1-1 suppressed HCC cell proliferation and cyclin D/E expression and promoted apoptosis and p21 expression. miR-494-3p was upregulated and TRIM36 was downregulated in HCC cells. Transfection with miR-494-3p mimic or sh-TRIM36 facilitated HCC cell proliferation and the expression of cyclin D/E protein but they inhibited apoptosis and p21 expression in the presence of EPS1-1. Overexpression of TRIM36 further consolidated EPS1-1-mediated inhibition of HCC proliferation, cyclin D/E, and the promotion of apoptosis and p21 expression. Those effects were reversed by miR-494-3p overexpression. TRIM36 was a target gene of miR-494-3p, and TRIM36 induced cyclin E ubiquitination. EPS1-1 suppressed cyclin E expression, promoted TRIM36 expression and tumor apoptosis, all of which were abrogated by increasing the expression of miR-494-3p in vivo. CONCLUSIONS EPS1-1 protected against HCC by limiting its proliferation and survival through the miR-494-3p/TRIM36 axis and by inducing cyclin E ubiquitination.
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Affiliation(s)
| | | | | | | | - Pengfei Rong
- Correspondence to: Pengfei Rong, Department of Radiology, The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China. ORCID: https://orcid.org/0000-0001-5473-1982. Tel: +86-18684706350, Fax: +86-731-88618411, E-mail:
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Saccon TD, Dhahbi JM, Schneider A, Nunez Lopez YO, Qasem A, Cavalcante MB, Sing LK, Naser SA, Masternak MM. Plasma miRNA Profile of Crohn's Disease and Rheumatoid Arthritis Patients. BIOLOGY 2022; 11:508. [PMID: 35453708 PMCID: PMC9033111 DOI: 10.3390/biology11040508] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/21/2022] [Accepted: 03/22/2022] [Indexed: 06/14/2023]
Abstract
Crohn's disease (CD) and rheumatoid arthritis (RA) are immune mediated inflammatory diseases. Several studies indicate a role for microRNAs (miRNAs) in the pathogenesis of a variety of autoimmune diseases, including CD and RA. Our study's goal was to investigate circulating miRNAs in CD and RA patients to identify potential new biomarkers for early detection and personalized therapeutic approaches for autoimmune diseases. For this study, subjects with CD (n = 7), RA (n = 8) and healthy controls (n = 7) were recruited, and plasma was collected for miRNA sequencing. Comparison of the expression patterns of miRNAs between CD and healthy patients identified 99 differentially expressed miRNAs. Out of these miRNAs, 4 were down regulated, while 95 were up regulated. Comparison of miRNAs between RA and healthy patients identified 57 differentially expressed miRNAs. Out of those, 12 were down regulated, while 45 were up regulated. For all the miRNAs down regulated in CD and RA patients, 420 GO terms for biological processes were similarly regulated between both groups. Therefore, the identification of new plasma miRNAs allows the emergence of new biomarkers that can assist in the diagnosis and treatment of CD and RA.
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Affiliation(s)
- Tatiana D. Saccon
- Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas 96010-610, Brazil;
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
| | - Joseph M. Dhahbi
- Department of Medical Education, School of Medicine, California University of Science & Medicine, San Bernardino, CA 92324, USA; (J.M.D.); (L.K.S.)
| | - Augusto Schneider
- Faculdade de Nutrição, Universidade Federal de Pelotas, Pelotas 96010-610, Brazil;
| | | | - Ahmad Qasem
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
| | - Marcelo B. Cavalcante
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
- Department of Obstetrics and Gynecology, Fortaleza University, Fortaleza 60811-905, Brazil
| | - Lauren K. Sing
- Department of Medical Education, School of Medicine, California University of Science & Medicine, San Bernardino, CA 92324, USA; (J.M.D.); (L.K.S.)
| | - Saleh A. Naser
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
| | - Michal M. Masternak
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (A.Q.); (M.B.C.); (S.A.N.)
- Department of Head and Neck Surgery, Poznan University of Medical Sciences, 61-701 Poznan, Poland
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Liu J, Sauer MA, Hussein SG, Yang J, Tenen DG, Chai L. SALL4 and microRNA: The Role of Let-7. Genes (Basel) 2021; 12:1301. [PMID: 34573282 PMCID: PMC8467721 DOI: 10.3390/genes12091301] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 12/11/2022] Open
Abstract
SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene family. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regarding how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as important regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize current knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.
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Affiliation(s)
- Jun Liu
- Department of Pathology, Brigham & Women’s Hospital, Boston, MA 02115, USA; (J.L.); (M.A.S.); (J.Y.)
| | - Madeline A. Sauer
- Department of Pathology, Brigham & Women’s Hospital, Boston, MA 02115, USA; (J.L.); (M.A.S.); (J.Y.)
| | | | - Junyu Yang
- Department of Pathology, Brigham & Women’s Hospital, Boston, MA 02115, USA; (J.L.); (M.A.S.); (J.Y.)
| | - Daniel G. Tenen
- Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore
- Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Li Chai
- Department of Pathology, Brigham & Women’s Hospital, Boston, MA 02115, USA; (J.L.); (M.A.S.); (J.Y.)
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Morishita A, Oura K, Tadokoro T, Fujita K, Tani J, Masaki T. MicroRNAs in the Pathogenesis of Hepatocellular Carcinoma: A Review. Cancers (Basel) 2021; 13:cancers13030514. [PMID: 33572780 PMCID: PMC7866004 DOI: 10.3390/cancers13030514] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers, and the prognosis for late-stage HCC remains poor. A better understanding of the pathogenesis of HCC is expected to improve outcomes. MicroRNAs (miRNAs) are small, noncoding, single-stranded RNAs that regulate the expression of various target genes, including those in cancer-associated genomic regions or fragile sites in various human cancers. We summarize the central roles of miRNAs in the pathogenesis of HCC and discuss their potential utility as valuable biomarkers and new therapeutic agents for HCC. Abstract Hepatocellular carcinoma (HCC) is the seventh most frequent cancer and the fourth leading cause of cancer mortality worldwide. Despite substantial advances in therapeutic strategies, the prognosis of late-stage HCC remains dismal because of the high recurrence rate. A better understanding of the etiology of HCC is therefore necessary to improve outcomes. MicroRNAs (miRNAs) are small, endogenous, noncoding, single-stranded RNAs that modulate the expression of their target genes at the posttranscriptional and translational levels. Aberrant expression of miRNAs has frequently been detected in cancer-associated genomic regions or fragile sites in various human cancers and has been observed in both HCC cells and tissues. The precise patterns of aberrant miRNA expression differ depending on disease etiology, including various causes of hepatocarcinogenesis, such as viral hepatitis, alcoholic liver disease, or nonalcoholic steatohepatitis. However, little is known about the underlying mechanisms and the association of miRNAs with the pathogenesis of HCC of various etiologies. In the present review, we summarize the key mechanisms of miRNAs in the pathogenesis of HCC and emphasize their potential utility as valuable diagnostic and prognostic biomarkers, as well as innovative therapeutic targets, in HCC diagnosis and treatment.
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Alshehri MA, Alshehri MM, Albalawi NN, Al-Ghamdi MA, Al-Gayyar MMH. Heparan sulfate proteoglycans and their modification as promising anticancer targets in hepatocellular carcinoma. Oncol Lett 2021; 21:173. [PMID: 33552290 PMCID: PMC7798035 DOI: 10.3892/ol.2021.12434] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 12/08/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of primary liver cancer. Despite advancements in the treatment strategies of HCC, there is an urgent requirement to identify and develop novel therapeutic drugs that do not lead to resistance. These novel agents should have the potential to influence the primary mechanisms participating in the pathogenesis of HCC. Heparan sulfate proteoglycans (HSPGs) are major elements of the extracellular matrix that perform structural and signaling functions. HSPGs protect against invasion of tumor cells by preventing cell infiltration and intercellular adhesion. Several enzymes, such as heparanase, matrix metalloproteinase-9 and sulfatase-2, have been reported to affect HSPGs, leading to their degradation and thus enhancing tumor invasion. In addition, some compounds that are produced from the degradation of HSPGs, including glypican-3 and syndecan-1, enhance tumor progression. Thus, the identification of enzymes that affect HSPGs or their degradation products in HCC may lead to the development of novel therapeutic targets. The present review discusses the main enzymes and compounds associated with HSPGs, and their involvement with the pathogenicity of HCC.
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Affiliation(s)
- Mohammed A Alshehri
- PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Moath M Alshehri
- PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Naif N Albalawi
- PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Moshari A Al-Ghamdi
- PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Mohammed M H Al-Gayyar
- PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.,Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.,Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
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Wang Y, Yin L. LINC00461 Promoted Endometrial Carcinoma Growth and Migration by Targeting MicroRNA-219-5p/Cyclooxygenase-2 Signaling Axis. Cell Transplant 2021; 30:963689721989616. [PMID: 33573388 PMCID: PMC7885031 DOI: 10.1177/0963689721989616] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 11/10/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022] Open
Abstract
Endometrial carcinoma (EC) ranks as the most common female genital cancer in developed countries. Lately, more and more long noncoding RNAs (lncRNAs) have been identified as vital regulators in numerous physiological and pathological processes, including EC. However, the expression pattern and precise functions of different lncRNAs in EC remain unclear. In this study, we reported LINC00461 was upregulated in EC patient tissues and cell lines. In addition, LINC00461 knockdown could remarkably suppress cell proliferation, cell cycle progression, cell migration, and promote cell apoptosis in EC cells. We discovered LINC00461 could sponge microRNA-219-5p (miR-219-5p) and suppress its expression, thereby upregulating expression level of miR-219-5p's target, cyclooxygenase-2 (COX-2). In vivo animal models, LINC00461 knockdown inhibited tumor growth by increasing miR-219-5p level and reducing COX-2 expression, thus confirming LINC00461 functions as an oncogene in EC. In this study, a novel regulatory role of LINC00461/miR-219-5p/COX-2 axis was systematically investigated in context of EC, with the aim to provide promising intervention targets for EC therapy from bench to clinic. [Formula: see text].
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Affiliation(s)
- Yu Wang
- Department of Obstetrics & Gynecology, Shengjing Hospital of China Medical University, Liaoning Province, PR China
| | - Lili Yin
- Department of Obstetrics & Gynecology, Shengjing Hospital of China Medical University, Liaoning Province, PR China
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Hussein NH, Amin NS, El Tayebi HM. GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets. Front Oncol 2020; 10:537311. [PMID: 33344222 PMCID: PMC7746843 DOI: 10.3389/fonc.2020.537311] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 10/19/2020] [Indexed: 12/22/2022] Open
Abstract
With millions of cases diagnosed annually and high economic burden to cover expensive costs, cancer is one of the most difficult diseases to treat due to late diagnosis and severe adverse effects from conventional therapy. This creates an urgent need to find new targets for early diagnosis and therapy. Progress in research revealed the key steps of carcinogenesis. They are called cancer hallmarks. Zooming in, cancer hallmarks are characterized by ligands binding to their cognate receptor and so triggering signaling cascade within cell to make response for stimulus. Accordingly, understanding membrane topology is vital. In this review, we shall discuss one type of transmembrane proteins: Glycosylphosphatidylinositol-Anchored Proteins (GPI-APs), with specific emphasis on those involved in tumor cells by evading immune surveillance and future applications for diagnosis and immune targeted therapy.
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Chitnis NS, Shieh M, Monos D. Regulatory noncoding RNAs and the major histocompatibility complex. Hum Immunol 2020; 82:532-540. [PMID: 32636038 DOI: 10.1016/j.humimm.2020.06.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/21/2020] [Accepted: 06/09/2020] [Indexed: 12/15/2022]
Abstract
The Major Histocompatibility Complex (MHC) is a 4 Mbp genomic region located on the short arm of chromosome 6. The MHC region contains many key immune-related genes such as Human Leukocyte Antigens (HLAs). There has been a growing realization that, apart from MHC encoded proteins, RNAs derived from noncoding regions of the MHC-specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs)-play a significant role in cellular regulation. Furthermore, regulatory noncoding RNAs (ncRNAs) derived from other parts of the genome fine-tune the expression of many immune-related MHC proteins. Although the field of ncRNAs of the MHC is a research area that is still in its infancy, ncRNA regulation of MHC genes has already been shown to be vital for immune function, healthy pregnancy and cellular homeostasis. Dysregulation of this intricate network of ncRNAs can lead to serious perturbations in homeostasis and subsequent disease.
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Affiliation(s)
- Nilesh Sunil Chitnis
- Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Mengkai Shieh
- Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Dimitri Monos
- Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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12
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Upregulation of microRNA-219-5p relieves ulcerative colitis through balancing the differentiation of Treg/Th17 cells. Eur J Gastroenterol Hepatol 2020; 32:813-820. [PMID: 32175983 PMCID: PMC7269018 DOI: 10.1097/meg.0000000000001712] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE This study aimed to investigate the specific regulatory roles of microRNA-219-5p (miR-219-5p) on ulcerative colitis (UC), and reveal the potential mechanisms relating with the differentiation of Treg/Th17 cells. METHODS The mouse model of chronic UC was established by oral administration of 3% dextran sodium sulfate for three cycles. After intravenous injected with lentivirus (LV)-miR-219-5p for 24 h, the disease activity index (DAI), colon length, as well as the serum levels of Interleukin (IL)-6, -17A, -21, and -23 were measured. In addition, the histopathological changes in colon tissues were observed by Hematoxylin-eosin staining. The differentiation of Treg/Th17 cells was detected by Flow cytometry, and the expression of retinoic acid-related orphan receptor (RORrt), signal transducer and activator of transcription 3 (STAT3), and forkhead box p3 (Foxp3) were detected by quantitative real-time PCR and Western blot. RESULTS MiR-219-5p was downregulated in colonic mucosal tissues of UC mice (P < 0.05). UC mice injected with LV-miR-219-5p exhibited significantly relieved histopathological changes of colon tissues, increased colon length, decreased DAI, as well as decreased serum levels of IL-6, -17A, -21, and -23 (P < 0.05). In addition, the injection of LV-miR-219-5p significantly increased the percentage of Treg cells via upregulating Foxp3, and decreased the percentage of Th17 cells via downregulating RORrt and STAT3 in UC mice (P < 0.05). CONCLUSION The upregulation of miR-219-5p relieved the colonic damage and inflammation of UC through balancing the differentiation of Treg/Th17 cells.
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13
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Wang Z, Li Y, Cao J, Zhang W, Wang Q, Zhang Z, Gao Z, Ye Y, Jiang K, Wang S. MicroRNA Profile Identifies miR-6165 Could Suppress Gastric Cancer Migration and Invasion by Targeting STRN4. Onco Targets Ther 2020; 13:1859-1869. [PMID: 32184620 PMCID: PMC7060782 DOI: 10.2147/ott.s208024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 02/11/2020] [Indexed: 12/24/2022] Open
Abstract
Background Recent studies showed that aberrant expression of miRNAs causes tumor-suppressing or promoting effects in various cancers including gastric cancer (GC). Our previous studies showed that lots of miRNAs and mRNA expressed differentially in GC and normal tissues. However, the critical miRNAs and mRNA need to be clarified. Materials and Methods Microarray sequencing was used to profile the differential expression of miRNAs and mRNA in GC and normal tissues. Bioinformatics analysis and database prediction were used to search the critical miRNAs and mRNA. Real-time quantitative polymerase chain reaction (RT-qPCR), luciferase reporter assay, immunohistochemistry (IHC), wound healing assay and transwell assay were used to clarify the relationship between the target miRNAs and mRNA. Statistical analysis was used to seek their value of diagnosis and prognosis. Results We identified microRNA-6165 (miR-6165) as a novel cancer-related miRNA in GC through high-throughput microarray sequencing. By bioinformatics analysis and luciferase reporter assay, we found STRN4 was the target of miR-6165. Via a series of cell experiments, we determined that miR-6165 suppressed GC cells migration and invasion by targeting STRN4. Also, we discovered the potential diagnosis and prognosis value of miR-6165 and STRN4. Conclusion It was found that miR-6165 might suppress GC migration and invasion by targeting STRN4 in vitro, and the further research should focus more on the potential diagnosis and prognosis value of miR-6165 and STRN4 in gastric cancer patients.
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Affiliation(s)
- Zhu Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Yang Li
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Jian Cao
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Wei Zhang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Quan Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Zhen Zhang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Zhidong Gao
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Yingjiang Ye
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Kewei Jiang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
| | - Shan Wang
- Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, People's Republic of China.,Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Peking University People's Hospital, Beijing 100044, People's Republic of China
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14
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Shi Y, Dai S, Qiu C, Wang T, Zhou Y, Xue C, Yao J, Xu Y. MicroRNA-219a-5p suppresses intestinal inflammation through inhibiting Th1/Th17-mediated immune responses in inflammatory bowel disease. Mucosal Immunol 2020; 13:303-312. [PMID: 31628427 DOI: 10.1038/s41385-019-0216-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 09/11/2019] [Accepted: 09/28/2019] [Indexed: 02/04/2023]
Abstract
MicroRNA (miR)-219a-5p has been implicated in the development of numerous progression of carcinoma and autoimmune diseases. However, whether miR-219a-5p is involved in the pathogenesis of inflammatory bowel disease (IBD) remains elusive. In this study, we demonstrated that miR-219a-5p expression was significantly decreased in the inflamed intestinal mucosa and peripheral blood (PB)-CD4+ T cells from patients with IBD. Proinflammatory cytokines (e.g., IL-6, IL-12, IL-23 and TNF-α) inhibited miR-219a-5p expression in CD4+ T cells in vitro. Lentivirus-mediated miR-219a-5p downregulation facilitated Th1/Th17 cell differentiation, whereas miR-219a-5p overexpression exerted an opposite effect. Luciferase assays confirmed that ETS variant 5 (ETV5) was a functional target of miR-219a-5p and ETV5 expression was significantly increased in the inflamed intestinal mucosa and PB-CD4+ T cells from IBD patients. ETV5 overexpression enhanced Th1/Th17 immune response through upregulating the phosphorylation of STAT3 and STAT4. Importantly, supplementation of miR-219a-5p ameliorated TNBS-induced intestinal mucosal inflammation, characterized by decreased IFN-γ+ CD4+ T cells and IL-17A+ CD4+ T cells infiltration in the colonic lamina propria. Our data thus reveal a novel mechanism whereby miR-219a-5p suppresses intestinal inflammation through inhibiting Th1/Th17-mediated immune responses. miR-219a-5p might be a target for the treatment of IBD.
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Affiliation(s)
- Yan Shi
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China
| | - Shenglan Dai
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China
| | - Caiyu Qiu
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China
| | - Tao Wang
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China
| | - Yong Zhou
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China
| | - Cuihua Xue
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China
| | - Jun Yao
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China.
| | - Yaping Xu
- Department of Gastroenterology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China.
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15
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Dong W, Wu P, Zhou D, Huang J, Qin M, Yang X, Wan M, Zong Y. Ultrasound-Mediated Gene Therapy of Hepatocellular Carcinoma Using Pre-microRNA Plasmid-Loaded Nanodroplets. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:90-107. [PMID: 31668943 DOI: 10.1016/j.ultrasmedbio.2019.09.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 09/19/2019] [Accepted: 09/20/2019] [Indexed: 05/19/2023]
Abstract
The PIK3 CA gene encodes the p110α protein subunit and is one of the most efficient cancer genes in solid and hematological tumors including hepatocellular carcinoma (HCC). There are currently ongoing therapies against tumors based on PIK3 CA inhibition. Because microRNAs (miRNAs) play an important role in post-transcriptional regulation and are also involved in the inhibition of PIK3 CA expression to suppress cancer cell proliferation, overexpression of tumor-suppressive miRNA is a promising therapeutic approach for HCC therapy. The successful and localized delivery of miRNA overexpression vectors (pre-miRNA plasmids) is very important in improving the therapeutic efficacy of this miRNA therapy strategy. In the study described here, submicron acoustic phase-shifted nanodroplets were used to efficiently deliver pre-miRNA plasmid in vitro and in vivo for HCC therapy under focused ultrasound (US) activation. Briefly, six miRNAs, inhibiting PIK3 CA and downregulated in HCC, were selected through summary and analysis of the currently existing literature data. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and cell apoptosis assay revealed that pre-miR-139, -203a, -378a and -422a plasmids among the six miRNA overexpression vectors could suppress growth of the hepatoma cell line SMMC-7721. These four pre-miRNA plasmids were then electrostatically adhered to positively charged lipid-shelled nanodroplets to obtain plasmid-loaded nanodroplets (PLNDs). The PLND-generated microbubbles oscillated and even collapsed under US exposure to release the loaded pre-miRNA plasmids and enhance their cellular uptake through consequent sonoporation, that is, formation of small pores on the cell membrane induced by the mechanical effects of PLND cavitation. Fluorescence microscopy results revealed that PLNDs could effectively deliver the aforementioned four pre-miRNA plasmids into SMMC-7721 cells in vitro under 1.2-MHz 60-cycle sinusoid US exposure with a peak negative pressure >5.5 MPa at a 40-Hz pulse repetition frequency. Plasmid delivery efficiency and cell viability positively correlated with the inertial cavitation dose that was determined mainly by peak negative pressure. Furthermore, PLNDs combined with US were evaluated in vivo to deliver these four pre-miRNAs plasmids and verify their therapeutic efficacy in subcutaneous tumor of the mouse xenograft HCC model. The results revealed that the PLNDs loaded with pre-miR-139 and -378a plasmids could effectively suppress tumor growth after US treatment. Thus, combination of pre-miRNA PLNDs with US activation seems to constitute a potential strategy for HCC therapy.
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Affiliation(s)
- Wei Dong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Pengying Wu
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Di Zhou
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Jixiu Huang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Mengfan Qin
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Xinxing Yang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China; Department of Ultrasound, First Affiliated Hospital of AFMU (Xijing Hospital), Air Force Medical University, Xi' an, China
| | - Mingxi Wan
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China
| | - Yujin Zong
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi' an Jiaotong University, Xi' an, China.
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16
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Ashrafizadeh M, Ahmadi Z, Farkhondeh T, Samarghandian S. Anti-tumor Activity of Propofol: A Focus on MicroRNAs. Curr Cancer Drug Targets 2020; 20:104-114. [PMID: 31657687 DOI: 10.2174/1568009619666191023100046] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 09/02/2019] [Accepted: 09/23/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND MicroRNAs are endogenous, short, non-coding RNAs with the length as low as 20 to 25 nucleotides. These RNAs are able to negatively affect the gene expression at the post-transcriptional level. It has been demonstrated that microRNAs play a significant role in cell proliferation, cell migration, cell death, cell differentiation, infection, immune response, and metabolism. Besides, the dysfunction of microRNAs has been observed in a variety of cancers. So, modulation of microRNAs is of interest in the treatment of disorders. OBJECTIVE The aim of the current review is to investigate the modulatory effect of propofol on microRNAs in cancer therapy. METHODS This review was performed at PubMed, SCOPUS and Web of Science data-bases using keywords "propofol', "microRNA", "cancer therapy", "propofol + microRNA" and "propofol + miR". RESULTS It was found that propofol dually down-regulates/upregulates microRNAs to exert its antitumor activity. In terms of oncogenesis microRNAs, propofol exert an inhibitory effect, while propofol significantly enhances the expression of oncosuppressor microRNAs. CONCLUSION It seems that propofol is a potential modulator of microRNAs and this capability can be used in the treatment of various cancers.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Zahra Ahmadi
- Department of Basic Science, Veterinary Medicine Faculty, Shushtar University, Khuzestan, Iran
| | - Tahereh Farkhondeh
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Saeed Samarghandian
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
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17
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Si A, Wang L, Miao K, Zhang R, Ji H, Lei Z, Cheng Z, Fang X, Hao B. miR-219 regulates liver cancer stem cell expansion via E-cadherin pathway. Cell Cycle 2019; 18:3550-3561. [PMID: 31724462 PMCID: PMC6927721 DOI: 10.1080/15384101.2019.1691762] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 10/03/2019] [Accepted: 10/06/2019] [Indexed: 02/06/2023] Open
Abstract
Liver cancer stem cells contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liverCSCs is not fully understood yet. Here we show that miR-219 is upregulated in liver CSCs. Knockdown of miR-219 attenuates the self-renewal and tumorigenicity of liver CSCs. Conversely, miR-219 overexpressing enhances the self-renewal and tumorigenicity of liver CSCs.Mechanistically,miR-219 downregulates E-cadherin via itsmRNA 3'UTR in liver CSCs. The correlation between miR-219 and E-cadherin is validated in human HCC tissues. Furthermore, the miR-219 expression determines the responses of hepatoma cells to sorafenib treatment. Our findings indicate that miR-219 plays a critical role in liver CSCs expansion and sorafenib response, rendering miR-219 as an optimal target for the prevention and intervention of HCC.Abbreviations: HCC: Hepatocellular carcinoma; CSCs: cancer stem cells; DMEM: Dulbecco's modified Eagle's medium; FBS: fetal bovine serum; OS: overall survival.
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Affiliation(s)
- Anfeng Si
- Department of Surgical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Longqi Wang
- Department of General Surgery I, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Kun Miao
- Oncology Department Ward, Tianchang People’s Hospital, Anhui, China
| | - Rongrong Zhang
- Department of General Surgery III, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Huiyu Ji
- Department of Surgical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Zhengqing Lei
- Department of General Surgery, the Affiliated Zhongda Hospital, Southeast University, Nanjing, China
| | - Zhangjun Cheng
- Department of General Surgery, the Affiliated Zhongda Hospital, Southeast University, Nanjing, China
| | - Xiangchun Fang
- Department of Surgical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Baobing Hao
- Department of Surgical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
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18
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Gong T, Ning X, Deng Z, Liu M, Zhou B, Chen X, Huang S, Xu Y, Chen Z, Luo R. Propofol-induced miR-219-5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3-mediated Wnt/β-catenin signalling activation. J Cell Biochem 2019; 120:16934-16945. [PMID: 31104336 DOI: 10.1002/jcb.28952] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 01/26/2019] [Accepted: 01/30/2019] [Indexed: 12/12/2022]
Abstract
Propofol is one of the most extensively used intravenous anaesthetic agents, which has been found to improve the surgical intervention outcome of several types of cancer, including hepatocellular carcinoma (HCC). Additionally, in vitro and in vivo experiments have also indicated that propofol affects the biological behaviour of HCC. However, the underlying mechanisms of the surgical resection of HCC with propofol have not been fully understood. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of HCC cells. Our results showed that treatment with propofol suppressed the proliferation, invasion and migration of HCC in vitro. The subcutaneous xenograft tumour and orthotopic xenograft tumour experiments in nude mice showed that propofol significantly decreased tumour volumes, growth rates and the liver orthotopic xenograft tumour in vivo. Furthermore, the underlying mechanism investigations of the suppressive effects of propofol on HCC cells revealed that propofol treatment upregulated the expression levels of the candidate tumour suppressor miR-219-5p. Silencing of propofol-induced miR-219-5p using anti-miR-219-5p abrogated the inhibitory effects on the proliferation, migration and invasion of HCC cells exerted by propofol treatment. Additionally, we demonstrated that propofol reversed the epithelial-mesenchymal transition of Huh7 and SMMC7721 cells via miR-219-5p induction. The molecular mechanism behind these findings is that propofol-induced miR-219-5p inhibits HCC cell progression by targeting glypican-3 and subsequently results in the inhibition of Wnt/β-catenin signalling. Taken together, our study provides new insights into the advantages of the surgical intervention of HCC with propofol anaesthetization.
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Affiliation(s)
- Ting Gong
- Department of Anesthesiology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Xue Ning
- Department of Anesthesiology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhiya Deng
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Pathophysiology, Guangdong Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, China
| | - Mingyu Liu
- Department of Endoscopy, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Beixian Zhou
- Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Cancer Center, Southern Medical University, Guangzhou, Guangdong, China
| | - Xijun Chen
- Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Cancer Center, Southern Medical University, Guangzhou, Guangdong, China
| | - Shisi Huang
- Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Cancer Center, Southern Medical University, Guangzhou, Guangdong, China
| | - Yan Xu
- Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Cancer Center, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongqing Chen
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Pathophysiology, Guangdong Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, China
| | - Rongcheng Luo
- Department of Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- Department of Cancer Center, Southern Medical University, Guangzhou, Guangdong, China
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19
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Xiao Y, Zhang S, Li Q, Liu Z, Mai W, Chen W, Lei J, Hu H. miR-219a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury via Impairing TP53BP2. Dig Dis Sci 2019; 64:2177-2186. [PMID: 30796685 DOI: 10.1007/s10620-019-05535-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 02/14/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatic ischemia/reperfusion (I/R) injury is a serious complication that occurs upon hypovolemic shock, liver resection, and transplantation. A significant age-dependent difference in the injury response to hepatic I/R in both human and animal models has been reported. Nevertheless, the molecular mechanism is currently unclear. AIMS To clarify the reason why aged animals or people were more vulnerable to hepatic I/R injury. METHODS In the present study, we found decreased miR-219a-5p expression in the old mice more vulnerable to hepatic I/R injury. Administrated with agomir-miR-219a-5p diminished the severity of hepatic I/R injury in old mice, as indicated by lower serum ALT and AST, oxidative parameters including MDA, TOA, and OSI, and decreased apoptotic cell number. The effect of miR-219a-5p was also confirmed in the H2O2-induced apoptosis model in AML-12 and NCTC1469 cells. After miR-219a-5p overexpression, two key apoptosis-related proteins Bax and P21, target genes of TP53, were decreased. Furthermore, TP53BP2 interacts with p53 family members and promotes their transcriptional activities toward pro-apoptosis genes. RESULTS RNA sequencing, western blot, and luciferase reporter assay proved that TP53BP2, a crucial TP53 transcriptional activity enhancer in vivo, was directly regulated by miR-219a-5p. CONCLUSIONS In summary, our study demonstrated that age-related miR-219a-5p can attenuate hepatic I/R injury through inhibiting TP53BP2 and downstream TP53-dependent apoptosis of hepatic cells in mice.
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Affiliation(s)
- Yu Xiao
- Department of Anesthesiology, Jiangxi Provincial Children's Hospital, 122 Yangming Road, Nanchang, 330006, Jiangxi Province, China
| | - Shouhua Zhang
- Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, 330006, Jiangxi Province, China
| | - Qiang Li
- Department of Anesthesiology, Jiangxi Provincial Children's Hospital, 122 Yangming Road, Nanchang, 330006, Jiangxi Province, China
| | - Zhiwen Liu
- Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, 330006, Jiangxi Province, China
| | - Wenli Mai
- Department of Oncology, Jiangxi Provincial Cancer Hospital, Nanchang, 330029, China
| | - Wen Chen
- Department of Oncology, Jiangxi Provincial Cancer Hospital, Nanchang, 330029, China
| | - Jun Lei
- Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, 330006, Jiangxi Province, China
| | - Huakun Hu
- Department of Anesthesiology, Jiangxi Provincial Children's Hospital, 122 Yangming Road, Nanchang, 330006, Jiangxi Province, China.
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20
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Ma Q. MiR-219-5p suppresses cell proliferation and cell cycle progression in esophageal squamous cell carcinoma by targeting CCNA2. Cell Mol Biol Lett 2019; 24:4. [PMID: 30766610 PMCID: PMC6362576 DOI: 10.1186/s11658-018-0129-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 12/04/2018] [Indexed: 12/20/2022] Open
Abstract
Background We investigated the potential regulatory role of miR-219-5p in esophageal squamous cell carcinoma (ESCC) and looked at the underlying mechanisms in ESCC. Methods Real-time PCR was used to determine the levels of miR-219-5p in ESCC tissues and cell lines. The effects of miR-219-5p and cyclin A2 (CCNA2) on cell proliferation and cell cycle progression were evaluated using MTT, colony formation and flow cytometry assays with ESCC cell lines EC9706 and TE-9. Bioinformatics techniques and the luciferase reporter assay were applied to validate CCNA2 as the miR-219-5p target in ESCC cells. The mRNA and protein levels of CCNA2 were measured using real-time PCR and western blotting. Results MiR-219-5p expression was significantly lower in ESCC tissues and cells than in healthy tissues. Upregulation of miR-219-5p repressed cell proliferation and induced cell cycle arrest at the G2/M phase. CCNA2 was identified and confirmed as a direct downstream target of miR-219-5p and its expression negatively correlated with miR-219-5p profiles in ESCC tissues. Knockdown of CCNA2 potentiated the effects of miR-219-5p on cell proliferation and cell cycle distribution. Conclusions Our results demonstrate that miR-219-5p might function as a tumor suppressor by directly targeting CCNA2 expression. It could serve as a new therapeutic target for ESCC.
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Affiliation(s)
- Qiang Ma
- Department of Oncology, People's Hospital of Xintai City, No. 1329 Xinfu Road, Xintai, 271200 Shandong Province China
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21
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Ma L, Ma J, Ou HL. MicroRNA‑219 overexpression serves a protective role during liver fibrosis by targeting tumor growth factor β receptor 2. Mol Med Rep 2018; 19:1543-1550. [PMID: 30592264 PMCID: PMC6390038 DOI: 10.3892/mmr.2018.9787] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 11/05/2018] [Indexed: 12/11/2022] Open
Abstract
Progressive liver fibrosis is the primary cause of liver cirrhosis and hepatocellular carcinoma, and leads to considerable morbidity and mortality. Recent studies have demonstrated that microRNAs (miRNAs or miRs) are associated with fibrotic processes in liver disorders, although the exact role of miR-219 remains unclear and the relevant mechanisms remain to be completely understood. To the best of our knowledge, the present study was the first to demonstrate the functional implications of miR-219 expression during liver fibrosis. The present study reported that miR-219 exhibited significantly reduced expression in serum from patients and that its expression was negatively associated with clinical stage. It was also demonstrated that miR-219 attenuated angiotensin II-induced expression of pro-fibrotic markers, including α-smooth muscle actin, atlastin GTPase 1 and collagen. Additionally, a CCl4-induced mouse liver injury model was used to demonstrate that miR-219 strongly suppressed liver fibrosis in vivo. Furthermore, the present study identified tumor growth factor β receptor 2 (TGFBR2) as a direct target gene of miR-219. In conclusion, the results of the present study revealed that miR-219 may regulate pro-fibrotic markers by directly targeting the TGFBR2 gene and the miR-219/TGFBR2 signaling pathway may be a potential therapeutic target for liver fibrosis.
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Affiliation(s)
- Li Ma
- Department of Liver Diseases, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
| | - Jian Ma
- Department of Endocrinology, The People's Hospital of Fenghua District, Ningbo, Zhejiang 315500, P.R. China
| | - Hong-Liang Ou
- Department of Liver Diseases, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
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22
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Li J, Chen W, Yi Y, Tong Q. miR‐219‐5p inhibits tau phosphorylation by targeting TTBK1 and GSK‐3β in Alzheimer's disease. J Cell Biochem 2018; 120:9936-9946. [PMID: 30556160 DOI: 10.1002/jcb.28276] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 11/19/2018] [Indexed: 12/31/2022]
Affiliation(s)
- Jing Li
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
| | - Weian Chen
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
| | - Yanhong Yi
- Department of Psychiatry, The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
| | - Qiuling Tong
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China
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23
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Sadri Nahand J, Bokharaei-Salim F, Salmaninejad A, Nesaei A, Mohajeri F, Moshtzan A, Tabibzadeh A, Karimzadeh M, Moghoofei M, Marjani A, Yaghoubi S, Keyvani H. microRNAs: Key players in virus-associated hepatocellular carcinoma. J Cell Physiol 2018; 234:12188-12225. [PMID: 30536673 DOI: 10.1002/jcp.27956] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Accepted: 11/19/2018] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.
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Affiliation(s)
- Javid Sadri Nahand
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | | | - Arash Salmaninejad
- Drug Applied Research Center, Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran.,Department of Medical Genetics, Medical Genetics Research Center, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolfazl Nesaei
- Department of Basic Sciences, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Fatemeh Mohajeri
- Department of Infectious Disease, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Azadeh Moshtzan
- Department of Infectious Disease, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Alireza Tabibzadeh
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | | | - Mohsen Moghoofei
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Arezo Marjani
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Shoeleh Yaghoubi
- Department of Infectious Disease, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Hossein Keyvani
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
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24
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The promising role of miR-296 in human cancer. Pathol Res Pract 2018; 214:1915-1922. [DOI: 10.1016/j.prp.2018.09.026] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 09/08/2018] [Accepted: 09/28/2018] [Indexed: 12/18/2022]
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25
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Xu L, Li T, Ding W, Cao Y, Ge X, Wang Y. Combined seven miRNAs for early hepatocellular carcinoma detection with chronic low-dose exposure to microcystin-LR in mice. THE SCIENCE OF THE TOTAL ENVIRONMENT 2018; 628-629:271-281. [PMID: 29438936 DOI: 10.1016/j.scitotenv.2018.02.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 01/31/2018] [Accepted: 02/02/2018] [Indexed: 06/08/2023]
Abstract
Aberrant miRNA expression has been detected in various tumor tissues, which may be considered as a marker for early cancer diagnosis. One miRNA has multiple downstream target genes, which can be regulated by multiple upstream other miRNAs. Hence, this dynamic regulation is likely characterized by volatility, and thus, finding the appropriate time point for tests becomes essential for the use of miRNAs as an early marker of tumor diagnosis. In this study, we established a chronic liver cancer progression model in mice by using low doses of the harmful substance microcystin-LR (MC-LR). On the basis of miRNAs microarray assay, we further tested seven miRNAs that showed characteristic expression changes in pre-hepatocarcinogenesis. Our results showed that the levels of four miRNAs (miR-122-5p, miR-125-5p, miR-199a-5p, and miR-503-5p) decreased dramatically, whereas those of two miRNAs (miR-222-5p and miR-590-5p) increased significantly in the early stages, which were all accompanied by an increase in atypia of hepatocytes. MiR-490-5p was a sensitive molecular, suitable only for evaluation of pathological changes in young mice. Therefore the combination the seven of miRNAs for a set may prove to be an effective method in healthy assessment of environmental toxicants for detection of hepatocarcinogenesis caused by hazardous materials.
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Affiliation(s)
- Lizhi Xu
- Basic Medical Education Center, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China.
| | - Tianfeng Li
- Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China; Center for Reproductive Medicine, The Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University, Shenzhen, Guangdong 518017, People's Republic of China
| | - Weidong Ding
- Basic Medical Education Center, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China
| | - Yu Cao
- Basic Medical Education Center, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China
| | - Xiaolong Ge
- Basic Medical Education Center, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China
| | - Yaping Wang
- Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, Jiangsu 210093, People's Republic of China
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26
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Zhao J, Gao S, Zhu Y, Shen X. Significant role of microRNA‑219‑5p in diabetic retinopathy and its mechanism of action. Mol Med Rep 2018; 18:385-390. [PMID: 29749515 DOI: 10.3892/mmr.2018.8988] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 01/29/2018] [Indexed: 11/06/2022] Open
Affiliation(s)
- Junying Zhao
- Department of Ophthalmology, Dahua Hospital, Shanghai 200237, P.R. China
| | - Sha Gao
- Department of Ophthalmology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Yanji Zhu
- Department of Ophthalmology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Xi Shen
- Department of Ophthalmology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
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27
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Cartier F, Indersie E, Lesjean S, Charpentier J, Hooks KB, Ghousein A, Desplat A, Dugot-Senant N, Trézéguet V, Sagliocco F, Hagedorn M, Grosset CF. New tumor suppressor microRNAs target glypican-3 in human liver cancer. Oncotarget 2018; 8:41211-41226. [PMID: 28476031 PMCID: PMC5522324 DOI: 10.18632/oncotarget.17162] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 03/25/2017] [Indexed: 12/22/2022] Open
Abstract
Glypican-3 (GPC3) is an oncogene, frequently upregulated in liver malignancies such as hepatocellular carcinoma (HCC) and hepatoblastoma and constitutes a potential molecular target for therapy in liver cancer. Using a functional screening system, we identified 10 new microRNAs controlling GPC3 expression in malignant liver cells, five of them e.g. miR-4510, miR-203a-3p, miR-548aa, miR-376b-3p and miR-548v reduce GPC3 expression. These 5 microRNAs were significantly downregulated in tumoral compared to non-tumoral liver and inhibited tumor cell proliferation. Interestingly, miR-4510 inversely correlated with GPC3 mRNA and protein in HCC samples. This microRNA also induced apoptosis of hepatoma cells and blocked tumor growth in vivo in the chick chorioallantoic membrane model. We further show that the tumor suppressive effect of miR-4510 is mediated through direct targeting of GPC3 mRNA and inactivation of Wnt/β-catenin transcriptional activity and signaling pathway. Moreover, miR-4510 up-regulated the expression of several tumor suppressor genes while reducing the expression of other pro-oncogenes. In summary, we uncovered several new microRNAs targeting the oncogenic functions of GPC3. We provided strong molecular, cellular and in vivo evidences for the tumor suppressive activities of miR-4510 bringing to the fore the potential value of this microRNA in HCC therapy.
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Affiliation(s)
- Flora Cartier
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Emilie Indersie
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Sarah Lesjean
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Justine Charpentier
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Katarzyna B Hooks
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Amani Ghousein
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Angélique Desplat
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Nathalie Dugot-Senant
- INSERM US005 - TBM Core, Service for Experimental Histopathology, F-33000 Bordeaux, France
| | - Véronique Trézéguet
- University of Bordeaux, F-33000 Bordeaux, France.,CNRS, UMR5248, Chimie & Biologie des Membranes & des Nano-objets, CBMN, F-33600 Pessac, France
| | - Francis Sagliocco
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Martin Hagedorn
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
| | - Christophe F Grosset
- University of Bordeaux, Inserm, Groupe de Recherche pour l'Etude du Foie, GREF, U1053, F-33076 Bordeaux, France.,University of Bordeaux, Inserm, Biothérapies des Maladies Génétiques Inflammatoires et Cancers, BMGIC, U1035, F-33076 Bordeaux, France
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28
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Yan F, Tu Z, Duan L, Wang D, Lin F. MicroRNA-383 suppresses cell proliferation and invasion in colorectal cancer by directly targeting paired box 6. Mol Med Rep 2018; 17:6893-6901. [PMID: 29512711 DOI: 10.3892/mmr.2018.8682] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 11/09/2017] [Indexed: 12/16/2022] Open
Abstract
Colorectal cancer (CRC) is the third-most prevalent cancer and the fourth‑most common cause of cancer-associated fatality worldwide. The expression and biological roles of microRNAs (miRNAs/miRs) in tumourigenesis, and their regulatory function in a number of biological processes correlated with cancer have been investigated. miR‑383 has been reported to be deregulated in several human cancer types. However, the involvement and effects of miR‑383 on CRC progression and its underlying mechanism remain unknown. Therefore, the present study aimed to examine miR‑383 expression, investigate the biological functions of miR‑383 and identify its mechanism of action in CRC cells. In the present study, miR‑383 was significantly downregulated in CRC tissues and cell lines. Low miR‑383 expression was negatively associated with tumour size, lymph node metastasis and TNM stage. Function experiments demonstrated that miR‑383 upregulation inhibited the proliferation and invasion of CRC cells. Paired box 6 (PAX6) was confirmed as a direct target of miR‑383. PAX6 was upregulated in CRC tissues and was negatively correlated with miR‑383 expression. Induced PAX6 overexpression effectively rescued the tumour‑suppressing roles of miR‑383 on CRC cell proliferation and invasion. These findings suggested that miR‑383 may act as a tumour suppressor in CRC by directly targeting PAX6 and may serve as a promising therapeutic target for CRC treatment.
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Affiliation(s)
- Fei Yan
- Department of Oncology, The Eighth People's Hospital of Shanghai, Shanghai 200233, P.R. China
| | - Zhiquan Tu
- Department of Oncology, The Eighth People's Hospital of Shanghai, Shanghai 200233, P.R. China
| | - Li Duan
- Department of Oncology, The Eighth People's Hospital of Shanghai, Shanghai 200233, P.R. China
| | - Dexing Wang
- Department of Oncology, The Eighth People's Hospital of Shanghai, Shanghai 200233, P.R. China
| | - Feng Lin
- Department of Oncology, The Eighth People's Hospital of Shanghai, Shanghai 200233, P.R. China
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29
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Hide T, Komohara Y, Miyasato Y, Nakamura H, Makino K, Takeya M, Kuratsu JI, Mukasa A, Yano S. Oligodendrocyte Progenitor Cells and Macrophages/Microglia Produce Glioma Stem Cell Niches at the Tumor Border. EBioMedicine 2018; 30:94-104. [PMID: 29559295 PMCID: PMC5952226 DOI: 10.1016/j.ebiom.2018.02.024] [Citation(s) in RCA: 89] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 02/19/2018] [Accepted: 02/28/2018] [Indexed: 01/23/2023] Open
Abstract
Glioblastoma (GBM) usually develops in adult brain white matter. Even after complete resection, GBM recurs around the tumor removal cavity, where GBM cells acquire chemo-radioresistance. Characterization of the tumor border microenvironment is critical for improving prognosis in patients with GBM. Here, we compared microRNA (miRNA) expression in samples from the tumor, tumor border, and periphery by miRNA microarray. The top three of miRNAs showing higher expression in the tumor border were related to oligodendrocyte differentiation, and pathologically oligodendrocyte lineage cells were increased in the border, where macrophages and microglia also colocalized. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells, similar to that produced by FGF1, EGF and HB-EGF, IL-1β, corresponding to OPCs and macrophages, respectively. Thus, OPCs and macrophages/microglia may form a glioma stem cell niche at the tumor border, representing a promising target for prevention of recurrence.
Most cases of glioblastoma recur in white matter around the removal cavity after total resection plus chemo-radiotherapy. miRNAs showing characteristically higher expression in the tumor border were related to oligodendrocyte differentiation. Increased oligodendrocyte progenitor cells and macrophages enhance stemness and chemo-radioresistance in glioma cells. Glioblastoma (GBM) occurs in adult brain and shows rapid growth and invasion. Despite intensive treatment, the mean 5-year survival rate is still <10%. Most cases of GBM recur locally even after total resection of gadolinium-enhanced lesions observed with MRI, indicating that chemo-radioresistant GBM cells survive there. MicroRNAs showing characteristically higher expression in the tumor border were related to oligodendrocyte differentiation. Oligodendrocyte progenitor cells (OPCs) and macrophages/microglia increased at tumor borders, and induced stemness and chemo-radioresistance in GBM cells in vivo. Thus, OPCs and macrophages/microglia formed characteristic microenvironments and may be promising targets to prevent GBM recurrence.
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Affiliation(s)
- Takuichiro Hide
- Department of Neurosurgery, Graduate School of Life Sciences, Kumamoto University, Japan.
| | - Yoshihiro Komohara
- Department of Cell Pathology, Graduate School of Life Sciences, Kumamoto University, Japan
| | - Yuko Miyasato
- Department of Cell Pathology, Graduate School of Life Sciences, Kumamoto University, Japan
| | - Hideo Nakamura
- Department of Neurosurgery, Graduate School of Life Sciences, Kumamoto University, Japan
| | - Keishi Makino
- Department of Neurosurgery, Graduate School of Life Sciences, Kumamoto University, Japan
| | - Motohiro Takeya
- Department of Cell Pathology, Graduate School of Life Sciences, Kumamoto University, Japan
| | - Jun-Ichi Kuratsu
- Department of Neurosurgery, Graduate School of Life Sciences, Kumamoto University, Japan
| | - Akitake Mukasa
- Department of Neurosurgery, Graduate School of Life Sciences, Kumamoto University, Japan
| | - Shigetoshi Yano
- Department of Neurosurgery, Graduate School of Life Sciences, Kumamoto University, Japan
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30
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Li J, Li L, Shen Y. Protective role of microRNA-219-5p inhibitor against spinal cord injury via liver receptor homolog-1/Wnt/β-catenin signaling pathway regulation. Exp Ther Med 2018; 15:3563-3569. [PMID: 29545884 DOI: 10.3892/etm.2018.5829] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 12/13/2017] [Indexed: 12/20/2022] Open
Abstract
The present study aimed to investigate the role of microRNA (miR)-219-5p in spinal cord injury (SCI) and to examine the underlying molecular mechanism. SCI rat and cell models were conducted in the current study, while reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of miR-219-5p in the SCI mice and neurons. Bioinformatics analysis was applied to predict the target genes of miR-219-5p, and dual-luciferase reporter assay was performed to verify the prediction. In addition, MTT assay and flow cytometry were conducted to determine the cell viability and cell apoptosis of the neurons, respectively. Western blot analysis was also performed to detect the expression of associated proteins. The study results demonstrated that miR-219-5p was highly expressed in SCI mice and neurons, and directly targets liver receptor homolog-1 (LRH-1). The neuron viability was significantly reduced by SCI, however, it was recovered upon transfection with an miR-219-5p inhibitor. Neuron apoptosis was notably induced by SCI and inhibited by miR-219-5p inhibition. The LRH-1/Wnt/β-catenin signaling pathway was also inhibited by SCI, while it was significantly enhanced by the miR-219-5p inhibitor. Furthermore, LRH-1 overexpression eliminated the effects of the miR-219-5p inhibitor on SCI. In conclusion, these data indicated that the miR-219-5p inhibitor served a protective role in SCI via regulating the LRH-1/Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Jie Li
- Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Liqiang Li
- Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Yong Shen
- Department of Spinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
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31
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Wei C, Zhang X, He S, Liu B, Han H, Sun X. MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway. Gene 2017; 637:25-32. [DOI: 10.1016/j.gene.2017.09.012] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/09/2017] [Accepted: 09/06/2017] [Indexed: 12/31/2022]
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32
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Jiang B, Li M, Ji F, Nie Y. MicroRNA-219 exerts a tumor suppressive role in glioma via targeting Sal-like protein 4. Exp Ther Med 2017; 14:6213-6221. [PMID: 29285179 DOI: 10.3892/etm.2017.5292] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 06/02/2017] [Indexed: 12/21/2022] Open
Abstract
MicroRNAs (miRs) serve important roles in the development and progression of various human cancer types, including glioma. Recently, miR-219 has been suggested to function as a tumor suppressor in glioma; however, the underlying mechanism remains largely unknown. The aim of this study was to investigate the regulatory mechanism of miR-219 in the malignant phenotypes of glioma cells. Quantitative polymerase chain reaction (qPCR) and western blotting were conducted to examine the mRNA and protein expression. An MTT assay, wound healing assay and Transwell assay were used to study cell proliferation, migration and invasion. The qPCR data indicated that the expression of miR-219 was significantly decreased in glioma tissues compared with normal brain tissues. In addition, a low expression of miR-219 was identified to be associated with an advanced pathological grade. In vitro experiments demonstrated that miR-219 was also downregulated in several common glioma cell lines, including A172, U87, U251 and U373, when compared with that in normal astrocytes. Ectopic expression of miR-219 caused a significant decrease in U87 cell proliferation, migration and invasion. Luciferase reporter assay data indicated that Sal-like protein 4 (SALL4) was a direct target gene of miR-219, while the protein expression of SALL4 was negatively regulated by miR-219 in U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and upregulation of SALL4 was associated with a higher pathological grade. Furthermore, overexpression of SALL4 significantly attenuated the suppressive effects of miR-219 on U87 cell proliferation, migration and invasion, suggesting that miR-219 serves a suppressive role in glioma growth and metastasis via targeting SALL4. Therefore, the present study highlighted the clinical significance of the miR-219/SALL4 axis in glioma.
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Affiliation(s)
- Botao Jiang
- Department of Neurology, First Hospital of Changsha, Changsha, Hunan 430100, P.R. China
| | - Min Li
- Department of Nephrology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Fang Ji
- Teaching and Research Office of Medical Imaging, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Yaxiong Nie
- Department of Neurology, First Affiliated Hospital of Nanhua University, Hengyang, Hunan 421001, P.R. China
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33
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Prognostic value of microRNAs in hepatocellular carcinoma: a meta-analysis. Oncotarget 2017; 8:107237-107257. [PMID: 29291025 PMCID: PMC5739810 DOI: 10.18632/oncotarget.20883] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Accepted: 08/29/2017] [Indexed: 12/20/2022] Open
Abstract
Background Numerous articles reported that dysregulated expression levels of miRNAs correlated with survival time of HCC patients. However, there has not been a comprehensive meta-analysis to evaluate the accurate prognostic value of miRNAs in HCC. Design Meta-analysis. Materials and Methods Studies, published in English, estimating expression levels of miRNAs with any survival curves in HCC were identified up until 15 April, 2017 by performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two independent authors. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS). Results 54 relevant articles about 16 miRNAs, with 6464 patients, were ultimately included. HCC patients with high expression of tissue miR-9 (HR = 2.35, 95% CI = 1.46–3.76), miR-21 (HR = 1.76, 95% CI = 1.29–2.41), miR-34c (HR = 1.64, 95% CI = 1.05–2.57), miR-155 (HR = 2.84, 95% CI = 1.46–5.51), miR-221 (HR = 1.76, 95% CI = 1.02–3.04) or low expression of tissue miR-22 (HR = 2.29, 95% CI = 1.63–3.21), miR-29c (HR = 1.35, 95% CI = 1.10–1.65), miR-34a (HR = 1.84, 95% CI = 1.30–2.59), miR-199a (HR = 2.78, 95% CI = 1.89–4.08), miR-200a (HR = 2.64, 95% CI = 1.86–3.77), miR-203 (HR = 2.20, 95% CI = 1.61–3.00) have significantly poor OS (P < 0.05). Likewise, HCC patients with high expression of blood miR-21 (HR = 1.73, 95% CI = 1.07–2.80), miR-192 (HR = 2.42, 95% CI = 1.15–5.10), miR-224 (HR = 1.56, 95% CI = 1.14–2.12) or low expression of blood miR-148a (HR = 2.26, 95% CI = 1.11–4.59) have significantly short OS (P < 0.05). Conclusions In conclusion, tissue miR-9, miR-21, miR-22, miR-29c, miR-34a, miR-34c, miR-155, miR-199a, miR-200a, miR-203, miR-221 and blood miR-21, miR-148a, miR-192, miR-224 demonstrate significantly prognostic value. Among them, tissue miR-9, miR-22, miR-155, miR-199a, miR-200a, miR-203 and blood miR-148a, miR-192 are potential prognostic candidates for predicting OS in HCC.
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34
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Sun X, Xu M, Liu H, Ming K. MicroRNA-219 is downregulated in non-small cell lung cancer and inhibits cell growth and metastasis by targeting HMGA2. Mol Med Rep 2017; 16:3557-3564. [PMID: 28714014 DOI: 10.3892/mmr.2017.7000] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Accepted: 04/21/2017] [Indexed: 11/05/2022] Open
Abstract
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-associated mortality worldwide. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, and accounts for ~85% of all lung cancer cases. An increasing number of studies suggest that microRNAs (miRs) may be involved in the regulation of NSCLC carcinogenesis and progression. However, the expression and function of miRNA-219 in NSCLC, and its underlying mechanisms of action, remain unknown. In the present study, miR-219 expression in NSCLC tissues and cell lines was determined using reverse transcription-quantitative polymerase chain reaction. Following transfection with miR-219 mimics, the effects of miR-219 overexpression on NSCLC cell proliferation, migration and invasion were examined. Furthermore, the miR-219 target in NSCLC was investigated. miR-219 was observed to be downregulated in NSCLC tissues and NSCLC cell lines. In addition, miR-219 was demonstrated to function as a tumor suppressor in NSCLC, through inhibiting cell proliferation, migration and invasion in vitro. Furthermore, high mobility group AT-hook 2 (HMGA2) was identified to be a direct target of miR-219 in NSCLC, and downregulation of HMGA2 suppressed NSCLC cell proliferation, migration and invasion in vitro. HMGA2 expression was upregulated in NSCLC tissues, and was inversely correlated with miR-219 expression. In conclusion, miR-219 functions as a tumor suppressor and may be important in inhibiting the growth and metastasis of NSCLC cells via directly targeting HMGA2. Therefore, miR-219 may present a potential novel therapeutic target for NSCLC.
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Affiliation(s)
- Xiaoping Sun
- Department of Emergency, Yidu Central Hospital of Weifang, Weifang Medical University, Weifang, Shandong 262500, P.R. China
| | - Min Xu
- Department of Emergency, Yidu Central Hospital of Weifang, Weifang Medical University, Weifang, Shandong 262500, P.R. China
| | - Haiyan Liu
- Department of Emergency, Yidu Central Hospital of Weifang, Weifang Medical University, Weifang, Shandong 262500, P.R. China
| | - Kunxiu Ming
- Department of Emergency Medicine, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
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35
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Gga-miR-219b targeting BCL11B suppresses proliferation, migration and invasion of Marek's disease tumor cell MSB1. Sci Rep 2017; 7:4247. [PMID: 28652615 PMCID: PMC5484716 DOI: 10.1038/s41598-017-04434-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 05/16/2017] [Indexed: 12/19/2022] Open
Abstract
Marek’s disease (MD), caused by Marek’s disease virus (MDV), is a lymphotropic neoplastic disease. Previous miRNAome analysis showed gga-miR-219b was significantly downregulated in MDV-induced lymphoma, and one of its potential target genes, B-cell chronic lymphocytic /lymphoma 11B (BCL11B) was predicted. In this study, we further investigated the function of gga-miR-219b, and the gain/loss of function assay showed gga-miR-219b inhibited cell migration and reduced cell proliferation by promoting apoptosis not by cell cycle arrest. Gga-miR-219b also suppressed expression of two cell invasion-related genes MMP2 and MMP9. The results indicated suppressive effect of gga-miR-219b on MD tumorigenesis. The gene BCL11B was verified as a direct target gene of gga-miR-219b. RNA interference was performed to block BCL11B. As expected, the effects triggered by BCL11B downregulation were in accordance with that triggered by gga-miR-219b overexpression, suggesting that BCL11B was a stimulative regulator of MD transformation. Moreover, both gga-miR-219b and BCL11B influenced the expression of Meq gene, the most important oncogene in MDV. Additionally, gene expression level of anti-apoptotic genes BCL2 and BCL2L1 was downregulated and pro-apoptotic gene TNFSF10 was upregulated in MSB1 cells with gga-miR-219b overexpression or BCL11B knockdown, which suggested gga-miR-219b promoted cell apoptosis via regulating gene expression in the apoptosis pathways.
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Zhou F, Shang W, Yu X, Tian J. Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med Res Rev 2017. [PMID: 28621802 DOI: 10.1002/med.21455] [Citation(s) in RCA: 248] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis. Mechanistic studies have revealed that GPC3 functions in HCC progression by binding to molecules such as Wnt signaling proteins and growth factors. Moreover, GPC3 has been used as a target for molecular imaging and therapeutic intervention in HCC. To date, GPC3-targeted magnetic resonance imaging, positron emission tomography, and near-infrared imaging have been investigated for early HCC detection, and various immunotherapeutic protocols targeting GPC3 have been developed, including the use of humanized anti-GPC3 cytotoxic antibodies, treatment with peptide/DNA vaccines, immunotoxin therapies, and genetic therapies. In this review, we summarize the current knowledge regarding the structure, function, and biology of GPC3 with a focus on its clinical potential as a diagnostic molecule and a therapeutic target in HCC immunotherapy.
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Affiliation(s)
- Fubo Zhou
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, 100853, China
| | - Wenting Shang
- Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, 100853, China
| | - Jie Tian
- Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
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Construction and analyses of the microRNA-target gene differential regulatory network in thyroid carcinoma. PLoS One 2017; 12:e0178331. [PMID: 28570571 PMCID: PMC5453480 DOI: 10.1371/journal.pone.0178331] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 05/11/2017] [Indexed: 12/13/2022] Open
Abstract
Thyroid-carcinoma (THCA) is the most common malignancy with an increasing incidence. Recent evidence has emphasized the role of microRNA (miRNA) in THCA. However, knowledge concerning the roles of miRNAs in THCA is still limited. We therefore use a miRNA-target gene differential regulatory network (MGDRN) to identify key miRNAs and characterize their synergistic regulation in THCA. Both miRNA-target gene interactions from multiple databases and negative expression correlations between miRNA-target genes were used to characterize the interactions. Then, two regulatory networks involving normal and tumor conditions were constructed, respectively. The MGDRN was finally constructed using different interactions between the above two regulatory networks. By analyzing topological features of the MGDRN, four miRNAs (hsa-mir-152-3p, hsa-mir-148a, hsa-mir-130b and hsa-mir-15b) are identified as key miRNAs in THCA. Over-expression of mir-152-3p inhibited proliferation and colony formation of TPC-1 cells. Furthermore, mir-152-3p negatively regulated ERBB3 by binding to the 3'-UTR of ERBB3, and down-regulation of ERBB3 by small interfering (si)RNAs inhibited proliferation and colony formation of TPC-1 cells, indicating that mir-152-3p acted as an anti-tumor miRNA by negatively regulating ERBB3. Finally, two synergistically dysregulated modules were identified which may contribute to the initiation and progression of THCA. Overall, the results provided a better understanding of the molecular basis of THCA, and suggested novel treatment strategies for this cancer.
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Zhu Y, Shi LY, Lei YM, Bao YH, Li ZY, Ding F, Zhu GT, Wang QQ, Huang CX. Radiosensitization effect of hsa-miR-138-2-3p on human laryngeal cancer stem cells. PeerJ 2017; 5:e3233. [PMID: 28533948 PMCID: PMC5436573 DOI: 10.7717/peerj.3233] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 03/27/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells. METHOD To investigate the radiational enhancement of hsa-miR-138-2-3p, we transfected hsa-miR-138-2-3p mimics that were synthesized based on the sequences of hsa-miR-138-2-3p in vitrointo human laryngeal CSCs (Hep-2, M2e, and TU212 cell lines) to make hsa-miR-138-2-3p overexpressed, and the tumorous specialities of CSCs, like cell proliferation, invasion, apoptosis, cell cycle arrest, and DNA damage were evaluated by CCK-8 assay, clone formation assay, invasion assay, flow cytometry, and comet assay. Furthermore, we explored the signal transduction pathways that regulated the cancer stem cell initiation, development, invasion, apoptosis and cell cycle arrest, which were controlled by hsa-miR-138-2-3p. RESULT Overexpressed hsa-miR-138-2-3p played a key role in many anti-cancer biological processes in human laryngeal CSCs: (1) it decreased laryngeal CSCs proliferation and invasion in response to radiotherapy; (2) it increased the proportion of early and late apoptosis in laryngeal CSCs after radiation, raised G1 phase arrest in laryngeal CSCs after radiation, and decreased the proportion of S stage cells of cell cycle that were related to radio-resistance in laryngeal CSCs; (3) it down-regulated the expression of β-catenin in Wnt signal pathway that was related to the tolerance of laryngeal CSCs to radiotherapy; (4) it down-regulated the expression of YAP1 in Hippo signal pathway that regulated cell proliferation, invasion and apoptosis; (5) it up-regulated the expression of p38 and JNK1 in MAPK signal pathway that was concerned to radio-sensitivity. CONCLUSION In the present study, it was found that hsa-miR-138-2-3p regulated the Wnt/β-catenin pathways, the Hippo/YAP1 pathways, and the MAPK/p38/JNK1 pathways that were involved in cell proliferation, invasion, apoptosis, cell cycle arrest, radio-resistance and radio-sensitivity in laryngeal CSCs. These results will be useful for a better understanding of the cell biology of hsa-miR-138-2-3p in laryngeal CSCs, and for serving hsa-miR-138-2-3p as a promising biomarker and as a target for diagnosis and for novel anti-cancer therapies for laryngeal cancers.
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Affiliation(s)
- Ying Zhu
- First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
| | - Li-Yun Shi
- Department of Immunology, School of Medical and Life Science, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yan-Min Lei
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yan-Hong Bao
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhao-Yang Li
- Department of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, China
| | - Fei Ding
- Department of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, China
| | - Gui-Ting Zhu
- Department of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, China
| | - Qing-Qing Wang
- Institute of Immunology, Zhejiang University, Hangzhou, China
| | - Chang-Xin Huang
- Department of Oncology, Affiliated Hospital with Hangzhou Normal University School of Medicine, Hangzhou, China
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Polymorphisms of pri-miR-219-1 are associated with the susceptibility and prognosis of non-small cell lung cancer in a Northeast Chinese population. Oncotarget 2017; 8:56533-56541. [PMID: 28915609 PMCID: PMC5593580 DOI: 10.18632/oncotarget.17035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 03/21/2017] [Indexed: 01/07/2023] Open
Abstract
Occurrence and development of non-small cell lung cancer (NSCLC) is a complex process affected both by gene and environment. Single nucleotide polymorphisms (SNPs) in microRNAs’ (miRNAs) biogenesis influenced the expression of mature miRNAs, further had an impact on risk of NSCLC. Our study focused on the correlation between rs213210, rs421446 or rs107822 polymorphisms in pri-miR-219-1 and susceptibility or prognosis of NSCLC in Chinese. A case-control study of 405 new-diagnosis patients and 405 controls was performed. Ten ml venous blood from each subject was collected for genotype test via using TaqMan allelic discrimination methodology and SPSS was performed for statistical analyses. We found that CC genotype in rs213210 (OR=3.462, 95%CI=2.222-5.394, P<0.001) compared with TT genotype and GG genotype in rs107822 (OR=3.553, 95%CI=2.329-5.419, P<0.001) compared with AA genotype showed significantly increased risk of NSCLC. Haplotype analysis showed that pri-miR-219-1 haplotype Crs213210Crs421446Grs107822 was a dangerous haplotype for lung cancer. And polymorphisms in pri-miR-219-1 have showed no relationship with overall survival of NSCLC. Overall, these findings firstly showed that rs213210 and rs107822 could be meaningful as genetic markers for lung cancer risk.
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Zhang X, Han K, Yuan DH, Meng CY. Overexpression of NAD(P)H: Quinone Oxidoreductase 1 Inhibits Hepatocellular Carcinoma Cell Proliferation and Induced Apoptosis by Activating AMPK/PGC-1α Pathway. DNA Cell Biol 2017; 36:256-263. [PMID: 28191864 DOI: 10.1089/dna.2016.3588] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Affiliation(s)
- Xin Zhang
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, China
| | - Kun Han
- Department of Gastroenterology, Xi'an Central Hospital, Xi'an, China
| | - Dong-hong Yuan
- Department of Gastroenterology, Affiliated Hospital of Yan'an University, Yan'an, China
| | - Cun-ying Meng
- Department of Gastroenterology, Affiliated Hospital of Yan'an University, Yan'an, China
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Sun B, Huang Z, Wang B, Yu Y, Lin S, Luo L, Wang Y, Huang Z. Significance of Glypican-3 (GPC3) Expression in Hepatocellular Cancer Diagnosis. Med Sci Monit 2017; 23:850-855. [PMID: 28207681 PMCID: PMC5325041 DOI: 10.12659/msm.899198] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Primary hepatocellular carcinoma (HCC) is a malignant tumor that is common China. Early diagnosis is of great significance for improving treatment efficiency. GPC3 level is closely related to HCC occurrence. This study investigated GPC3 expression in HCC patient serum and tissue, and assessed the significance of GPC3 combined AFP detection in HCC diagnosis. MATERIAL AND METHODS A total of 76 HCC patients in our hospital were enrolled. Immunohistochemistry was applied to test GPC3 expression in cancer tissue and para-carcinoma tissue. ELISA and RT-PCR were used to detect GPC3 and AFP level in serum. The significance of GPC3 single or combined AFP detection in HCC diagnosis was analyzed. RESULTS Immunohistochemistry showed that the GPC3 positive expression rate was obviously elevated in HCC tissue (P<0.01). Combination detection of AFP and GPC3 presented significantly higher sensitivity and specificity in HCC than single AFP or GPC3 detection. ELISA showed no significant difference in sensitivity, specificity, or accuracy compared with RT-PCR. CONCLUSIONS Serum GPC3 was overexpressed in HCC patients. Combination detection of serum AFP and GPC3 can enhance accuracy and efficacy of HCC diagnosis.
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Affiliation(s)
- Bin Sun
- Department of Interventional Radiology, The First People's Hospital of Guiyang, Guiyang, Guizhou, China (mainland)
| | - Zhi Huang
- Department of Interventional Radiology, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - Bi Wang
- Department of Prepotency, Maternal and Child Health Hospital of Guiyang City, Guiyang, Guizhou, China (mainland)
| | - Yanglong Yu
- Department of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China (mainland)
| | - Shihai Lin
- Department of Interventional Radiology, The First People's Hospital of Guiyang, Guiyang, Guizhou, China (mainland)
| | - Lei Luo
- Department of Interventional Radiology, The First People's Hospital of Guiyang, Guiyang, Guizhou, China (mainland)
| | - Yuzhu Wang
- Department of Interventional Radiology, The First People's Hospital of Guiyang, Guiyang, Guizhou, China (mainland)
| | - Zheng Huang
- Department of Interventional Radiology, The First People's Hospital of Guiyang, Guiyang, Guizhou, China (mainland)
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Abstract
Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth in vitro and in vivo and also alters chemo sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with critical functions in tumor progression. In addition, microRNA (miRNA) expression changes are also involved in chemo-resistance. Herein, we assessed microRNA (miRNA) profiling to identify the functional network and biological pathways altered in SPARC-overexpressed medulloblastoma cells. A total of 27 differentially expressed miRNAs were identified between the control and SPARC-overexpressed samples. Potential messenger RNA (mRNA) targets of the differentially expressed miRNA were identified using Ingenuity Pathway Analysis (IPA). Network-based functional analyses were performed on the available human protein interaction and miRNA-gene association data to highlight versatile miRNAs among the significantly deregulated miRNAs using the IPA, and the biological pathway analysis using the PANTHER web-based tool. We have identified six miRNAs (miR-125b1*, miR-146a-5p, miR-181a-5p, miR-204-5p, miR-219-5p and miR-509-3p) that are associated with SPARC sensitivity by comparison of miRNA expression patterns from the SPARC treated cells with the control cells. Furthermore, pathway enrichment analysis outline that these six microRNAs mainly belong to biological processes related to cancer related signaling pathways. Collectively, these studies have the potential to indicate novel biomarkers for treatment response and can also be applied to develop novel therapeutic treatment for medulloblastoma.
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Montalbano M, Georgiadis J, Masterson AL, McGuire JT, Prajapati J, Shirafkan A, Rastellini C, Cicalese L. Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (Review). Oncol Rep 2017; 37:1291-1300. [PMID: 28098909 DOI: 10.3892/or.2017.5387] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 01/12/2017] [Indexed: 12/17/2022] Open
Abstract
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome. Additionally, certain cancer types have displayed a downregulation of GPC-3 expression. More recently, the protein has been evaluated as a useful marker for hepatocellular carcinoma (HCC) due to its increased expression in the liver during times of growth. In contrast, the GPC-3 marker is not detectable in normal adult liver. Immunotherapy that targets GPC-3 and its affiliated proteins is under investigation as these new biomarkers may hold potential for the detection and treatment of HCC and other diseases in which GPC-3 may be overexpressed. Studies have reported that an overexpression of GPC-3 in HCC predicts a poorer prognosis. This prognostic value further pushes the question regarding GPC-3's role in the regulation and progression of HCC. This review will summarize the current knowledge regarding the clinical aspects of GPC-3, while also synthesizing the current literature with the aim to better understand this molecule's biological interactions at a molecular level, not only in the liver, but in the rest of the body as well. Due to the existing gap in the literature surrounding GPC-3, we believe further investigation of function, structure and domains, cellular localization, and other subfields is warranted to evaluate the protein as a whole, as well as its part in the study of HCC.
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Affiliation(s)
- Mauro Montalbano
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Jeremias Georgiadis
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Ashlyn L Masterson
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Joshua T McGuire
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Janika Prajapati
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Ali Shirafkan
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Cristiana Rastellini
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Luca Cicalese
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA
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Wang Q, Zhu L, Jiang Y, Xu J, Wang F, He Z. miR-219-5p suppresses the proliferation and invasion of colorectal cancer cells by targeting calcyphosin. Oncol Lett 2017; 13:1319-1324. [PMID: 28454255 DOI: 10.3892/ol.2017.5570] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2015] [Accepted: 10/27/2016] [Indexed: 11/06/2022] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs involved in an array of biological processes, and their dysregulation is associated with tumor development and progression. One such miRNA, miR-219-5p, is abnormally expressed in patients with colorectal cancer (CRC). In the present study, reverse transcription-quantitative polymerase chain reaction was performed to measure miR-219-5p expression in cells from both CRC tumors, and surrounding healthy tissue. MTT and invasion assays were used to determine the role of miR-219-5p in regulating CRC cell proliferation and invasion, respectively. A luciferase assay was then performed to assess the binding of miR-219-5p to the CAPS gene that encodes calcyphosin protein. The present study confirmed that miR-219-5p expression is significantly downregulated in CRC tissue. miR-219-5p knockdown promoted the growth of HCT-8 cells and increased the expression of calcyphosin protein (CAPS). On the other hand, overexpressing miR-219-5p inhibited HCT-8 cell growth and invasion, and downregulated CAPS expression. In addition, CAPS was identified as the functional downstream target of miR-219-5p by directly targeting its 3'-untranslated region. Therefore, miR-219-5p may function as a tumor suppressor by decreasing CAPS expression, and subsequently inhibit tumor proliferation and invasion. These results indicate that novel therapeutic strategies that increase miR-219-5p expression may be developed to treat CRC.
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Affiliation(s)
- Quhui Wang
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Lirong Zhu
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Yasu Jiang
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Junfei Xu
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Feiran Wang
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Zhixian He
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
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Zhang S, Liu X, Liu J, Guo H, Xu H, Zhang G. PGC-1 alpha interacts with microRNA-217 to functionally regulate breast cancer cell proliferation. Biomed Pharmacother 2017; 85:541-548. [DOI: 10.1016/j.biopha.2016.11.062] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 11/14/2016] [Accepted: 11/14/2016] [Indexed: 12/21/2022] Open
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Yao M, Wang L, Fang M, Zheng W, Dong Z, Yao D. Advances in the study of oncofetal antigen glypican-3 expression in HBV-related hepatocellular carcinoma. Biosci Trends 2016; 10:337-343. [PMID: 27795482 DOI: 10.5582/bst.2016.01176] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Early specific diagnosis and effective treatment of hepatocellular carcinoma (HCC) are crucial. Expression of membrane-associated heparan sulfate proteoglycan glypican-3 (GPC-3) was recently found to increase as part of the malignant transformation of hepatocytes, and this increase is especially marked in patients with hepatitis B virus (HBV) infection, periportal cancerous embolus, or extra-hepatic metastasis. According to data from basic and clinical studies, the oncofetal antigen GPC-3 is a highly specific diagnostic biomarker of HCC and an indicator of its prognosis, and GPC-3 is also a promising target molecule for HCC gene therapy since it may play a crucial role in cell proliferation, metastasis, and invasion and it may mediate oncogenesis and oncogenic signaling pathways. This review summarizes recent advances in the use of oncofetal antigen GPC-3 to diagnose HBV-related HCC, estimate its prognosis, and its targeted therapy.
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Affiliation(s)
- Min Yao
- Department of Immunology, Medical School of Nantong University
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Li C, Dong J, Han Z, Zhang K. MicroRNA-219-5p Represses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Targeting the LRH-1/Wnt/β-Catenin Signaling Pathway. Oncol Res 2016; 25:617-627. [PMID: 27983934 PMCID: PMC7841075 DOI: 10.3727/096504016x14768374457986] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
MicroRNAs (miRNAs) are reportedly involved in gastric cancer development and progression. In particular, miR-219-5p has been reported to be a tumor-associated miRNA in human cancer. However, the role of miR-219-5p in gastric cancer remains unclear. In this study, we investigated for the first time the potential role and underlying mechanism of miR-219-5p in the proliferation, migration, and invasion of human gastric cancer cells. miR-219-5p was found to be markedly decreased in gastric cancer tissues and cell lines compared with adjacent tissues and normal gastric epithelial cells. miR-219-5p mimics or anti-miR-219-5p was transfected into gastric cancer cell lines to overexpress or suppress miR-219-5p expression, respectively. Results showed that miR-219-5p overexpression significantly decreased the proliferation, migration, and invasion of gastric cancer cells. Conversely, miR-219-5p suppression demonstrated a completely opposite effect. Bioinformatics and luciferase reporter assays indicated that miR-219-5p targeted the 3′-untranslated region of the liver receptor homolog-1 (LRH-1), a well-characterized oncogene. Furthermore, miR-219-5p inhibited the mRNA and protein levels of LRH-1. LRH-1 mRNA expression was inversely correlated with miR-219-5p expression in gastric cancer tissues. miR-219-5p overexpression significantly decreased the Wnt/β-catenin signaling pathway in gastric cancer cells. Additionally, LRH-1 restoration can markedly reverse miR-219-5p-mediated tumor suppressive effects. Our study suggests that miR-219-5p regulated the proliferation, migration, and invasion of human gastric cancer cells by suppressing LRH-1. miR-219-5p may be a potential target for gastric cancer therapy.
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Affiliation(s)
- Chunsheng Li
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China
| | - Jingrong Dong
- Endoscopic Center, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, P.R. China
| | - Zhenqi Han
- Endoscopic Center, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, P.R. China
| | - Kai Zhang
- Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China
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Wei W, Zhang Q, Wang Z, Yan B, Feng Y, Li P. miR-219-5p inhibits proliferation and clonogenicity in chordoma cells and is associated with tumor recurrence. Oncol Lett 2016; 12:4568-4576. [PMID: 28105164 PMCID: PMC5228431 DOI: 10.3892/ol.2016.5222] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Accepted: 09/16/2016] [Indexed: 01/01/2023] Open
Abstract
Chordoma is a rare malignant bone tumor that is usually localized to the skull base, vertebral column and sacrum. The transcription factor brachyury, which is encoded by the T gene, has a critical role in the development and progression of chordoma, although the mechanisms underlying brachyury regulation remain unclear. The aim of the current study was to identify and characterize microRNAs (miRs) that regulate brachyury expression in chordoma. MicroRNAs that target brachyury were predicted using miRanda and TargetScan. Using reverse transcription-quantitative polymerase chain reaction, miR-219-5p was shown to be significantly downregulated in chordoma tissues and the U-CH2 chordoma cell lines. A dual-luciferase reporter assay was used to validate the inhibitory effect of miR-219-5p on brachyury mRNA expression. The expression level of brachyury was downregulated in U-CH2 cells following transfection with miR-219-5p mimics and upregulated following transfection with the miR-219-5p inhibitor. The effects of miR-219-5p on the proliferation and clonogenicity of chordoma cells were assessed using cell counting kit-8, EdU and clone formation assays. These in vitro results indicated that miR-219-5p may have an important role in regulating the cell proliferation and clonogenicity of human chordoma cells, potentially by targeting brachyury. Furthermore, the associations between the expression levels of miR-219-5p and various clinicopathological factors were analyzed, and miR-219-5p expression was shown to correlate with tumor extent and recurrence. These results suggested that miR-219-5p functions as a tumor suppressor in chordoma and, therefore, that miR-219-50 may be a potential target for therapeutic intervention.
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Affiliation(s)
- Wei Wei
- Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China
| | - Qiuhang Zhang
- Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China
| | - Zhenlin Wang
- Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China
| | - Bo Yan
- Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China
| | - Yanjun Feng
- Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China
| | - Pu Li
- Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China
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Yin Z, Cui Z, Li H, Ren Y, Qian B, Rothman N, Lan Q, Zhou B. Polymorphisms in miR-135a-2, miR-219-2 and miR-211 as well as their interaction with cooking oil fume exposure on the risk of lung cancer in Chinese nonsmoking females: a case-control study. BMC Cancer 2016; 16:751. [PMID: 27663200 PMCID: PMC5035461 DOI: 10.1186/s12885-016-2784-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 09/15/2016] [Indexed: 12/26/2022] Open
Abstract
Background The associations between microRNAs and lung cancer have received increasing attention. This study assess the association between polymorphisms in miR-135a-2, miR-219-2 and miR-211 genes and the risk of lung cancer, as well as the gene–environment interaction between these polymorphisms and cooking oil fume exposure. Methods A case–control study featuring 268 cases and 266 controls was conducted. The associations of miR-135a-2 rs10459194, miR-219-2 rs10988341 and miR-211 rs1514035 polymorphisms with the risk of lung cancer were analyzed. The gene–environment interactions were also reported on both additive and multiplicative scales. Results There were no statistically significant associations between the single-nucleotide polymorphisms (SNPs) and lung cancer or lung adenocarcinoma. The individuals with both a risk genotype of miRNA SNPs and exposure to a risk factor (cooking oil fumes) were at higher risk of lung cancer than those with only one of these two risk factors (odd ratios of 2.208, 1.285 and 1.813 for miR-135a-2 rs10459194; 2.164, 1.209 and 1.806 for miR-219-2 rs10988341; and 2.122, 1.146 and 1.725 for miR-211 rs1514035, respectively). However, the measures of biological interaction indicate that there was no such interaction between the three SNPs and exposure to cooking oil fumes on an additive scale. Logistic regression models also suggested that the gene–environment interactions were not statistically significant on a multiplicative scale. Conclusions There were no significant associations between the polymorphisms in miRNAs (miR-26a-1 rs7372209, miR-605 rs2043556 and miR-16-1 rs1022960) and the risk of lung cancer in the Chinese nonsmoking female population. The interactions between these polymorphisms in miRNAs and cooking oil fume exposure were also not statistically significant.
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Affiliation(s)
- Zhihua Yin
- Department of Epidemiology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.,Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China
| | - Zhigang Cui
- School of Nursing, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China
| | - Hang Li
- Department of Epidemiology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.,Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China
| | - Yangwu Ren
- Department of Epidemiology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.,Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China
| | - Biyun Qian
- Department of Epidemiology, School of Public Health, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Nathaniel Rothman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA
| | - Qing Lan
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA
| | - Baosen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China. .,Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.
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50
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Zhu XT, Yuan JH, Zhu TT, Li YY, Cheng XY. Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3. FEBS J 2016; 283:3739-3754. [DOI: 10.1111/febs.13839] [Citation(s) in RCA: 119] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Revised: 07/16/2016] [Accepted: 08/26/2016] [Indexed: 12/30/2022]
Affiliation(s)
- Xiao-ting Zhu
- Department of Anatomy, Histology and Embryology; Shanghai Jiao Tong University School of Medicine; China
| | - Ji-hang Yuan
- Department of Medical Genetics; Second Military Medical University; Shanghai China
| | - Teng-teng Zhu
- Department of Anatomy, Histology and Embryology; Shanghai Jiao Tong University School of Medicine; China
| | - Yang-yang Li
- Department of Anatomy, Histology and Embryology; Shanghai Jiao Tong University School of Medicine; China
| | - Xiao-yang Cheng
- Department of Anatomy, Histology and Embryology; Shanghai Jiao Tong University School of Medicine; China
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