MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1

Technol Cancer Res Treat. 2021 Jan-Dec:20:15330338211033074. doi: 10.1177/15330338211033074.

Abstract

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown.

Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells.

Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3'UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration.

Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

Keywords: N-myc downstream regulated gene 1; hepatocellular carcinoma; miR-133b; miR-188-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Movement
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Transfection

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • MIRN133 microRNA, human
  • MIRN188 microRNA, human
  • MicroRNAs
  • N-myc downstream-regulated gene 1 protein