MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

Cell Physiol Biochem. 2018;46(6):2261-2270. doi: 10.1159/000489594. Epub 2018 May 3.

Abstract

Background/aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has the third highest mortality rate among all cancers. MicroRNAs are a class of endogenous, single-stranded short noncoding RNAs. The purpose of this study was to study the role of microRNA-873 in HCC.

Methods: The expression of miRNA-873 and tumor suppressor in lung cancer 1 (TSLC1) in HCC tissues and cell lines was detected by real-time quantitative RT-PCR (RT-qPCR) or western blot. A CCK-8 assay was used to examine cell proliferation; flow cytometry was used to assess the cell cycle; the Transwell migration assay was used to test for metastasis. Luciferase assays were performed to assess whether TSLC1 was a novel target of miRNA-873.

Results: We showed that miRNA-873 was upregulated in HCC tissues and cell lines compared with the normal control. Knockdown of miRNA-873 inhibited the growth and metastasis of HepG2 and accelerated G1 phase arrest, while overexpression of miRNA-873 had the opposite effect. The dual-luciferase reporter assays revealed that TSLC1 was a novel target of miRNA-873. Further study showed that TSLC1 was decreased in HCC tissues and cell lines. There was a negative correlation between the expression levels of TSLC1 and miRNA-873. The effect of miRNA-873 overexpression was neutralized by TSLC1. We also found that miRNA-873 activated the PI3K/AKT/mTOR signaling pathway and promoted HCC.

Conclusions: Our data demonstrated that miRNA-873 promoted HCC progression by targeting TSLC1 and provided a new target for the therapy of HCC.

Keywords: Hepatocellular carcinoma; Mirna-873; PI3K/AKT/mTOR; TSLC1.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Adhesion Molecule-1 / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology

Substances

  • CADM1 protein, human
  • Cell Adhesion Molecule-1
  • MIRN873 microRNA, human
  • MicroRNAs