miR‑29a suppresses the growth and metastasis of hepatocellular carcinoma through IFITM3

Yiming Liang1, Enliang Li2, Jiaqi Min1

  • 1Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Oncology Reports
|October 2, 2018
PubMed

Insights

Interferon-induced transmembrane protein 3 (IFITM3) is upregulated and miR-29a is downregulated in hepatocellular carcinoma (HCC), promoting tumor progression. Targeting this miR-29a/IFITM3 axis offers potential new therapies for HCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Interferon-induced transmembrane protein 3 (IFITM3) is implicated in various cancers, but its role in hepatocellular carcinoma (HCC) remains unclear.
  • MicroRNAs (miRNAs) regulate gene expression and are critical in cancer development; miR-29a is aberrantly expressed in HCC.
  • The relationship between IFITM3 and miR-29a in HCC has not been previously reported.

Purpose of the Study:

  • To investigate the expression of IFITM3 and miR-29a in HCC tissues.
  • To explore the correlation between IFITM3 and miR-29a and their impact on HCC biological behavior and patient prognosis.
  • To elucidate the underlying molecular mechanism involving IFITM3 and miR-29a in HCC progression.

Main Methods:

  • Quantitative analysis of IFITM3 and miR-29a expression in HCC tissues.
  • In vitro experiments involving IFITM3 knockdown and overexpression in HCC cell lines.
  • Dual-luciferase reporter gene assay to confirm the direct targeting of IFITM3 by miR-29a.

Main Results:

  • IFITM3 was upregulated and miR-29a downregulated in HCC tissues, correlating with tumor size, multifocality, and venous invasion.
  • IFITM3 expression was negatively correlated with miR-29a expression; both were associated with poor HCC prognosis.
  • IFITM3 knockdown inhibited HCC cell migration, invasion, and proliferation while promoting apoptosis, mirroring the effects of miR-29a upregulation. Conversely, IFITM3 overexpression in normal cells increased invasion, migration, and proliferation while decreasing apoptosis.
  • IFITM3 was identified as a direct target gene of miR-29a.

Conclusions:

  • The miR-29a/IFITM3 axis plays a crucial role in regulating the migration, invasion, proliferation, and apoptosis of HCC cells.
  • Aberrant expression of miR-29a and IFITM3 is linked to HCC development and progression.
  • miR-29a and IFITM3 represent potential novel therapeutic targets for hepatocellular carcinoma.

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