MicroRNA-1178-3p suppresses the growth of hepatocellular carcinoma by regulating transducin (beta)-like 1 X-linked receptor 1

Hum Cell. 2021 Sep;34(5):1466-1477. doi: 10.1007/s13577-021-00565-5. Epub 2021 Jun 14.

Abstract

MicroRNAs (miRNAs) are implicated in various cancer-relevant cellular processes, including cell proliferation, migration, invasion, and angiogenesis. However, the function of miRNAs in hepatocellular cancer (HCC) has not been fully clarified. This study aimed to investigate the role of miR-1178-3p in HCC metastasis and try to reveal the potential mechanism. In the present study, we found that miR-1178-3p was down-regulated, while TBL1XR1 was up-regulated in HCC cancer tissues by bioinformatics analysis and RT-PCR. We further confirmed the connection of miR-1178-3p and TBL1XR1 using dual-luciferase reporter (DLR) assay. Moreover, gain- and loss-of-function experiments demonstrated that overexpress miR-1178-3p inhibited cell proliferation, migration, and invasion in HCC cells and reduced the xenograft tumor growth and angiogenesis by regulating the TBL1XR1/PI3K/Akt axis. Our results indicated that the novel identified miR-1178-3p functions as a tumor suppressor in HCC through regulating TBL1XR1/PI3K/Akt pathway, and these findings could be a valid molecular target for liver cancer therapy.

Keywords: Angiogenesis; Hepatocellular cancer; TBL1XR1; miR-1178-3p.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Neovascularization, Pathologic / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Transducin / genetics*
  • Transducin / metabolism*
  • Up-Regulation / genetics

Substances

  • MIRN1178 microRNA, human
  • MicroRNAs
  • TBL1X protein, human
  • Proto-Oncogene Proteins c-akt
  • Transducin