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Rnd3/RhoE Is down-regulated in hepatocellular carcinoma and controls cellular invasion

Florence Grise1, Sandra Sena, Aurélien Bidaud-Meynard

  • 1INSERM, Physiopathologie du Cancer du Foie, U1053, Bordeaux, France.

Hepatology (Baltimore, Md.)
|January 12, 2012
PubMed
Abstract

Insights

Rnd3 (RhoE) expression is significantly reduced in hepatocellular carcinoma (HCC). This down-regulation promotes tumor cell invasion and metastasis, indicating Rnd3 may act as a metastasis suppressor gene in HCC.

Area of Science:

  • Molecular biology
  • Oncology
  • Cell biology

Background:

  • Rnd3 (RhoE) is an atypical Rho GTPase.
  • Rnd3 expression is altered in hepatocellular carcinoma (HCC).

Purpose of the Study:

  • To investigate the role of Rnd3 in HCC progression.
  • To determine the functional impact of Rnd3 down-regulation on tumor cell behavior.

Main Methods:

  • Analysis of public microarray data.
  • Quantitative real-time polymerase chain reaction (qRT-PCR).
  • Immunohistochemistry and western blotting.
  • Cell culture experiments with Rnd3 overexpression and silencing.
  • Short interfering RNA (siRNA) mediated gene knockdown.

Main Results:

  • Rnd3 expression is significantly down-regulated in HCC compared to non-tumor liver tissue.
  • Lower Rnd3 expression correlates with invasive HCC tumors and satellite nodules.
  • Rnd3 manipulation affects 3D cell motility; knockdown increases invasion.
  • Rnd3 down-regulation is linked to epithelial-mesenchymal transition (EMT) via ZEB2 and miR-200b/c.
  • Rnd3 knockdown-induced invasion is Rac1-dependent and matrix-metalloproteinase-independent.

Conclusions:

  • Rnd3 down-regulation confers an invasive advantage to HCC hepatocytes.
  • Rnd3 functions as a potential metastasis suppressor gene in HCC.

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