MiR-384 regulated IRS1 expression and suppressed cell proliferation of human hepatocellular carcinoma

Tumour Biol. 2016 Oct;37(10):14165-14171. doi: 10.1007/s13277-016-5233-5. Epub 2016 Aug 19.

Abstract

Acquired evidence indicated that microRNAs (miRNAs) played essential roles in cancer development, including hepatocellular carcinoma (HCC). Functions and mechanisms of miRNAs involved in HCC remain largely unknown. Here, we found that miR-384 was significantly downregulated in HCC cells and tissues by RT-PCR. Gain and loss of function studies revealed that miR-384 significantly suppressed HCC cell proliferation. Insulin receptor substrate 1(IRS1) was identified as a direct and functional target of miR-384. Moreover, miR-384 decreased IRS1 expression, subsequently downregulating cyclin D1 and upregulating p21 and p-Rb expression. In addition, promotion of cell proliferation caused by miR-384-in was counteracted by silencing IRS1 expression with siRNAs. Taken together, our data provided convincing evidence that miR-384 exerted suppressive effect on HCC cell proliferation through the direct inhibition of IRS1 expression, suggesting miR-384 may serve as a potential therapeutic target for HCC.

Keywords: Cell proliferation; Human hepatocellular carcinoma; IRS1; miR-384.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Proliferation
  • Humans
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • MicroRNAs
  • RNA, Messenger