Rnd3/RhoE Is down-regulated in hepatocellular carcinoma and controls cellular invasion
Abstract
We performed a review of public microarray data that revealed a significant down-regulation of Rnd3 expression in hepatocellular carcinoma (HCC), as compared to nontumor liver. Rnd3/RhoE is an atypical RhoGTPase family member because it is always under its active GTP-bound conformation and not sensitive to classical regulators. Rnd3 down-regulation was validated by quantitative real-time polymerase chain reaction in 120 independent tumors. Moreover, Rnd3 down-expression was confirmed using immunohistochemistry on tumor sections and western blotting on human tumor and cell-line extracts. Rnd3 expression was significantly lower in invasive tumors with satellite nodules. Overexpression and silencing of Rnd3 in Hep3B cells led to decreased and increased three-dimensional cell motility, respectively. The short interfering RNA-mediated down-regulation of Rnd3 expression induced a loss of E-cadherin at cell-cell junctions that was linked to epithelial-mesenchymal transition through the up-regulation of the zinc finger E-box binding homeobox protein, ZEB2, and the down-regulation of miR-200b and miR-200c. Rnd3 knockdown mediated tumor hepatocyte invasion in a matrix-metalloproteinase-independent, and Rac1-dependent manner. Conclusion: Rnd3 down-regulation provides an invasive advantage to tumor hepatocytes, suggesting that RND3 might represent a metastasis suppressor gene in HCC.
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BibTeX
@article{grise2026rnd3rhoe,
title = {{Rnd3/RhoE Is down-regulated in hepatocellular carcinoma and controls cellular invasion}},
author = {Florence Grise and Sandra Sena and Aurélien Bidaud-Meynard and Jessica Baud and Jean-Baptiste Hiriart and Kassem Makki and Nathalie Dugot-Senant and Cathy Staedel and Paulette Bioulac-Sage and Jessica Zucman-Rossi and Jean Rosenbaum and Violaine Moreau},
journal = {Hepatology},
year = {2026},
month = sep,
doi = {10.1002/hep.25568},
url = {https://hal.science/hal-05738661v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Rnd3/RhoE Is down-regulated in hepatocellular carcinoma and controls cellular invasion
AU - Florence Grise
AU - Sandra Sena
AU - Aurélien Bidaud-Meynard
AU - Jessica Baud
AU - Jean-Baptiste Hiriart
AU - Kassem Makki
AU - Nathalie Dugot-Senant
AU - Cathy Staedel
AU - Paulette Bioulac-Sage
AU - Jessica Zucman-Rossi
AU - Jean Rosenbaum
AU - Violaine Moreau
PY - 2026
DA - 2026/09/04
JO - Hepatology
DO - 10.1002/hep.25568
UR - https://hal.science/hal-05738661v1
AB - We performed a review of public microarray data that revealed a significant down-regulation of Rnd3 expression in hepatocellular carcinoma (HCC), as compared to nontumor liver. Rnd3/RhoE is an atypical RhoGTPase family member because it is always under its active GTP-bound conformation and not sensitive to classical regulators. Rnd3 down-regulation was validated by quantitative real-time polymerase chain reaction in 120 independent tumors. Moreover, Rnd3 down-expression was confirmed using immunohistochemistry on tumor sections and western blotting on human tumor and cell-line extracts. Rnd3 expression was significantly lower in invasive tumors with satellite nodules. Overexpression and silencing of Rnd3 in Hep3B cells led to decreased and increased three-dimensional cell motility, respectively. The short interfering RNA-mediated down-regulation of Rnd3 expression induced a loss of E-cadherin at cell-cell junctions that was linked to epithelial-mesenchymal transition through the up-regulation of the zinc finger E-box binding homeobox protein, ZEB2, and the down-regulation of miR-200b and miR-200c. Rnd3 knockdown mediated tumor hepatocyte invasion in a matrix-metalloproteinase-independent, and Rac1-dependent manner. Conclusion: Rnd3 down-regulation provides an invasive advantage to tumor hepatocytes, suggesting that RND3 might represent a metastasis suppressor gene in HCC.
SN - 0270-9139
SN - 1527-3350
ER -