MicroRNA-645 represses hepatocellular carcinoma progression by inhibiting SOX30-mediated p53 transcriptional activation

Int J Biol Macromol. 2019 Jan:121:214-222. doi: 10.1016/j.ijbiomac.2018.10.032. Epub 2018 Oct 9.

Abstract

Amount of evidence demonstrate that aberrant microRNAs (miRNAs) are involved in tumorigenesis and progression in hepatocellular carcinoma (HCC). Among them, miR-645 is recently recognized as cancer-related miRNA and its significance in HCC remains largely unknown. In this study, we reported for the first that miR-645 expression was markedly elevated in HCC tissues and cell lines, and its up-regulation was associated with malignant clinical features, including tumor size and venous infiltration and poor prognosis. Our data revealed that miR-645 promoted cell proliferation, colony formation and inhibited apoptosis by gain- and loss-of function experiments in vitro. In vivo assays showed that miR-645 overexpression enhanced tumor growth. Moreover, miR-645 directly bound to the SOX30 3'-UTR and post-transcriptionally repressed SOX30 expression in HCC cells. Furthermore, miR-645 inversely correlated with SOX30 expression in HCC tissues. Restoration of SOX30 expression at least partially abolished the biological effects of miR-645 on HCC cells. SOX30 regulated HCC progression through aberrant activation of p53 by directly binding to its promoter. Taken together, this research supports the first evidence that miR-645 exerts an oncogenic role in HCC progression and may be a therapeutic target for HCC treatment.

Keywords: Hepatocellular carcinoma; P53; Proliferation; SOX30; miR-645.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression*
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • SOX Transcription Factors / metabolism*
  • Transcriptional Activation / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • MIRN645 microRNA, human
  • MicroRNAs
  • SOX Transcription Factors
  • SOX30 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins