miR-3682-3p Activated by c-Myc Aggravates the Migration and Stemness in Hepatocellular Carcinoma Cells by Regulating PTEN/PI3K/AKT/β-Catenin Signaling

Dig Dis. 2023;41(3):447-457. doi: 10.1159/000527800. Epub 2022 Nov 10.

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cancer worldwide. miRNA has been linked to cancer processes. We want to figure out what the underlying mechanism and functions of miR-3682-3p are in HCC.

Methods: Thirty pairs of tumor tissues and adjacent tissues were obtained from HCC patients. mRNA and protein expressions were detected by quantitative real-time PCR and Western blot, respectively. The migration and invasion were measured using transwell or wound-healing assays. Dual luciferase and ChIP assays were utilized to detect gene interactions.

Results: miR-3682-3p was highly expressed in HCC tissues and cell lines. Silencing of miR-3682-3p inhibited cell migration and invasion, increased E-cadherin expression, and decreased N-cadherin, vimentin, and snail expressions, as well as the SOX2, OCT4, and Bmi1 expression, thereby restraining EMT and stemness of HCC in vitro. miR-3682-3p was positively activated by c-Myc and could directly target PTEN to activate PI3K/AKT/β-catenin pathway. In addition, inhibition of PTEN weakened the anti-migration and anti-stemness effects of miR-3682-3p downregulation in HCC cells.

Conclusion: miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/β-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.

Keywords: Hepatocellular carcinoma; Metastasis; Stemness; c-Myc; miR-3682-3p.

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • beta Catenin
  • MicroRNAs
  • PTEN protein, human
  • PTEN Phosphohydrolase