MicroRNA-33b regulates hepatocellular carcinoma cell proliferation, apoptosis, and mobility via targeting Fli-1-mediated Notch1 pathway

J Cell Physiol. 2020 Oct;235(10):7635-7644. doi: 10.1002/jcp.29673. Epub 2020 Apr 2.

Abstract

MicroRNAs (miRNAs) have been confirmed to play pivotal roles in hepatocellular carcinoma (HCC) carcinogenesis. However, the underlying function of microRNA-33b (miR-33b) in HCC remains unclear. Here, we found that miR-33b level was significantly reduced in both HCC tissues and tumor cell lines. Further, luciferase reporter assay and western blot analysis confirmed that Friend leukemia virus integration 1 (Fli-1) was a direct target of miR-33b. Overexpression of miR-33b dramatically suppressed HCC tumor cell proliferation and cell mobility, but facilitated tumor cell apoptosis in vitro. Besides, restoration of Fli-1 partially attenuated miR-33b-mediated inhibition of cell growth and metastasis via activating Notch1 signaling and its downstream effectors. Our findings demonstrate the important role of miR-33b/Fli-1 axis in HCC progression and provide novel therapeutic candidates for HCC clinical treatment.

Keywords: Fli-1; Notch1; carcinogenesis; hepatocellular carcinoma; miR-33b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver / pathology
  • MicroRNAs / genetics*
  • Microfilament Proteins / genetics*
  • Receptor, Notch1 / genetics*
  • Signal Transduction / genetics
  • Trans-Activators / genetics*

Substances

  • FLII protein, human
  • MicroRNAs
  • Microfilament Proteins
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Trans-Activators