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MicroRNA-455-3p functions as a tumor suppressor by targeting HDAC2 to regulate cell cycle in hepatocellular carcinoma

Fuquan Ma1, Jin Huang1, Weizhi Li1

  • 1Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Environmental Toxicology
|March 14, 2022
PubMed

Insights

MicroRNA-455-3p (miR-455-3p) acts as a tumor suppressor in hepatocellular carcinoma (HCC). It inhibits HCC cell growth and migration by targeting HDAC2, thereby activating the p53 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent cancer with limited treatment options.
  • MicroRNAs (miRNAs) are emerging as critical regulators in cancer development and potential therapeutic targets.
  • The specific role of miR-455-3p in HCC progression requires further elucidation.

Purpose of the Study:

  • To investigate the function and mechanism of miR-455-3p in hepatocellular carcinoma.
  • To determine the relationship between miR-455-3p, HDAC2, and the p53 signaling pathway in HCC.

Main Methods:

  • Quantitative real-time PCR to assess miR-455-3p and HDAC2 expression levels.
  • In vitro assays (proliferation, migration, apoptosis) in HCC cell lines (HepG2, Huh7).
  • In vivo mouse xenograft model to evaluate tumorigenesis.
  • Western blotting to analyze protein expression (CDK6, cyclin D1, p53 pathway proteins).

Main Results:

  • miR-455-3p was significantly downregulated in HCC tissues and cell lines.
  • Overexpression of miR-455-3p suppressed HCC cell proliferation and migration, and induced apoptosis.
  • miR-455-3p directly targeted HDAC2, inhibiting its expression.
  • HDAC2 overexpression reversed the effects of miR-455-3p, while p53 inhibition abolished them.
  • miR-455-3p suppressed tumor growth in vivo.

Conclusions:

  • miR-455-3p functions as a tumor suppressor in HCC by targeting HDAC2.
  • The miR-455-3p/HDAC2 axis regulates HCC cell proliferation, migration, and apoptosis via the p53 pathway.
  • miR-455-3p represents a potential therapeutic target for hepatocellular carcinoma treatment.
Keywords:
HDAC2cell cyclehepatocellular carcinomamicroRNA-455-3pthe p53 pathway

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