11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The miR-383-LDHA axis regulates cell proliferation, invasion and glycolysis in hepatocellular cancer

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective(s):

          To explore the correlation between expression patterns and functions of miR-383 and LDHA in hepatocellular cancer (HCC).

          Materials and Methods:

          We detected the expression of miR-383 and LDHA in 30 HCC tissues and their matched adjacent normal tissues using qRT-PCR. Then we performed MTT assay, foci formation assay, transwell migration assay, glucose uptake assay and lactate production assay to explore the function of miR-383 in cell proliferation, invasion and glycolysis in HCC cell lines. Luciferase reporter assay was used to explore whether LDHA was a target gene of miR-383. Western blot and qRT-PCR were used to further confirm LDHA was targeted by miR-383. Then the above functional experiments were repeated to see whether the function of LDHA could be inhibited by miR-383.

          Results:

          The results of qRT-PCR showed that miR-383 was down-regulated in HCC tissues compared with their matched adjacent normal tissues. Functional experiments showed that overexpression of miR-383 significantly suppressed cell proliferation, invasion and glycolysis. Luciferase reporter assay showed LDHA was a target gene of miR-383 and expression of LDHA was inversely correlated with that of miR-383 in HCC. Besides, increased cell proliferation, invasion and glycolysis triggered by LDHA could be inhibited by overexpression of miR-383 in HCC cell lines.

          Conclusion:

          Our study proved that miR-383 is down-regulated in HCC and acts as a tumor suppressor through targeting LDHA. Targeting the miR-383-LDHA axis might be a promising strategy in HCC treatment.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: not found

          MicroRNAs in human cancer.

          Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20-23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the translation and stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is initiated through specific base-pairing interactions between the 5' end ("seed" region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3' UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer, we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition, examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Hepatocellular carcinoma review: current treatment, and evidence-based medicine.

            Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Multiple treatment options are available for HCC including curative resection, liver transplantation, radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agent like sorafenib. The treatment of HCC depends on the tumor stage, patient performance status and liver function reserve and requires a multidisciplinary approach. In the past few years with significant advances in surgical treatments and locoregional therapies, the short-term survival of HCC has improved but the recurrent disease remains a big problem. The pathogenesis of HCC is a multistep and complex process, wherein angiogenesis plays an important role. For patients with advanced disease, sorafenib is the only approved therapy, but novel systemic molecular targeted agents and their combinations are emerging. This article provides an overview of treatment of early and advanced stage HCC based on our extensive review of relevant literature.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1

              Our previous studies have shown that microRNA-383 (miR-383) expression is downregulated in the testes of infertile men with maturation arrest (MA). However, the underlying mechanisms of miR-383 involved in the pathogenesis of MA remain unknown. In this study, we showed that downregulation of miR-383 was associated with hyperactive proliferation of germ cells in patients with mixed patterns of MA. Overexpression of miR-383 in NT2 (testicular embryonal carcinoma) cells resulted in suppression of proliferation, G1-phase arrest and induction of apoptosis, whereas silencing of miR-383 reversed these effects. The effects of miR-383 were mediated through targeting a tumor suppressor, interferon regulatory factor-1 (IRF1), and miR-383 was negatively correlated with IRF1 protein expression in vivo. miR-383 inhibited IRF1 by affecting its mRNA stability, which subsequently reduced the levels of the targets of IRF1, namely cyclin D1, CDK2 and p21. Downregulation of IRF1 or cyclin D1, but not that of CDK2, enhanced miR-383-mediated effects, whereas silencing of p21 partially inhibited the effects of miR-383. Moreover, miR-383 downregulated CDK4 by increasing proteasome-dependent degradation of CDK4, which in turn resulted in an inhibition of phosphorylated retinoblastoma protein (pRb) phosphorylation. These results suggest that miR-383 functions as a negative regulator of proliferation by targeting IRF1, in part, through inactivation of the pRb pathway. Abnormal testicular miR-383 expression may potentiate the connections between male infertility and testicular germ cell tumor.
                Bookmark

                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Iran )
                2008-3866
                2008-3874
                February 2017
                : 20
                : 2
                : 187-192
                Affiliations
                [1 ]Department of Infectious Disease, XiangTan City Central Hospital, XiangTan, People’s Republic of China
                [2 ]Edong Healthcare City Hospital of Traditional Chinese Medicine, Inefections Disease Hospital, Huangshi, People’s Republic of China
                [3 ]Cancer Research Institute, University of South China, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Hengyang, People’s Republic of China
                Author notes
                [* ] Corresponding author: Zhiwei Zhang. Cancer Research Institute, University of South China, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Hengyang, People’s Republic of China, 421001. Tel/Fax: +86-734-8281510; email: nhdxzzw@ 123456qq.com
                Article
                IJBMS-20-187
                10.22038/ijbms.2017.8246
                5339660
                28293396
                b6ab8b6f-ea7c-49d2-b0d6-106760191504
                Copyright: © Iranian Journal of Basic Medical Sciences

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 April 2016
                : 20 October 2016
                Categories
                Original Article

                hepatocellular cancer,ldha,mir-383
                hepatocellular cancer, ldha, mir-383

                Comments

                Comment on this article