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

Title	Rnd3/RhoE is down-regulated in hepatocellular carcinoma and controls cellular invasion
Publication Type	Journal Article
Year of Publication	2012
Authors	Grise, F, Sena S, Bidaud-Meynard A, Baud J, Hiriart J-B, Makki K, Dugot-Senant N, Staedel C, Bioulac-Sage P, Zucman-Rossi J, Rosenbaum J, Moreau V
Journal	Hepatology
Pagination	n/a - n/a
Date Published	2012
Abstract	We performed a review of public microarray data that revealed a significant down-regulation of Rnd3 expression in hepatocellular carcinoma as compared to non-tumor liver. Rnd3/RhoE is an atypical RhoGTPase family member, as it is always under its active GTP-bound conformation and not sensitive to classical regulators. Rnd3 down-regulation was validated by quantitative real time PCR in a hundred independent tumors. Moreover, Rnd3 down-expression was confirmed using immunohistochemistry on tumor sections and Western blot 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 3D cell motility, respectively. The siRNA-mediated down-regulation of Rnd3 expression induced 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 hepatocellular carcinoma.
DOI	10.1002/hep.25568
Short Title	Hepatology