miR-382-5p promotes cell invasion in hepatocellular carcinoma by targeting PTEN to activate PI3K/Akt signaling pathway

World J Surg Oncol. 2022 Jun 2;20(1):175. doi: 10.1186/s12957-022-02638-7.

Abstract

Purpose: This study aimed at investigating miR-382-5p expression in tissues and cell lines with hepatocellular carcinoma (HCC), its effects on the invasion of HCC cells, and related mechanisms.

Methods: miR-382-5p expression in HCC tissues, adjacent tissues, cell lines of normal hepatic cells, and HCC cells were detected by qRT-PCR, indicating its upregulation or downregulation in HCC cell lines (Hep3B and HCCLM3). The effect of miR-382-5p on cell invasion was observed by the Transwell experiment. The targeting relationship of miR-382-5p and the phosphatase and tensin homolog (PTEN) was analyzed using bioinformatics tools and the luciferase reporter gene assay. The correlation between miR-382-5p and PTEN was analyzed with Spearman correlation analysis. PTEN expression was observed after upregulation and downregulation of miR-382-5p expression. The effect of miR-382-5p on the expression of key proteins in PI3K/Akt signaling pathway was determined by Western blot.

Results: miR-382-5p expression was upregulated in both HCC tissues and cell lines (both P<0.05). Upregulation or downregulation of miR-382-5p significantly promoted or inhibited the invasion of cell lines, Hep3B, and HCCLM3. The luciferase reporter gene assay confirmed that PTEN is a target of miR-382-5p. The expressions of miR-382-5p and PTEN were negatively correlated (r=-0.742, P<0.001). Upregulation of PTEN expression by plasmid transfection can reverse the invasive effect of miR-382-5p on HCC cells. Upregulation of miR-382-5p can activate PI3K/Akt signaling pathway, and downregulation of miR-382-5p can inhibit PI3K/Akt signaling pathway.

Conclusions: miR-382-5p can activate the PI3K/Akt signaling pathway by targeting PTEN and promote HCC cell invasion.

Keywords: Hepatocellular carcinoma; Invasion; PI3K/Akt; PTEN; miR-382-5p.

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Liver Neoplasms* / pathology
  • Luciferases / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • MIRN382 microRNA, human
  • MicroRNAs
  • Luciferases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human