Overexpression of miR-21 promotes an in vitro metastatic phenotype by targeting the tumor suppressor RHOB

Metastasis is a multistep process that involves the deregulation of oncogenes and tumor suppressors beyond changes required for primary tumor formation. RHOB is known to have tumor suppressor activity, and its knockdown is associated with more aggressive tumors as well as changes in cell shape, migr...

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Bibliographic Details
Published in:Molecular cancer research 2010-05, Vol.8 (5), p.691-700
Main Authors: Connolly, Erin C, Van Doorslaer, Koenraad, Rogler, Leslie E, Rogler, Charles E
Format: Article
Language:English
Subjects:
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - secondary
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic - genetics
Genes, Tumor Suppressor - physiology
Hep G2 Cells
Humans
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
MicroRNAs - biosynthesis
MicroRNAs - genetics
MicroRNAs - physiology
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - physiopathology
Phenotype
rhoB GTP-Binding Protein - genetics
rhoB GTP-Binding Protein - metabolism
rhoB GTP-Binding Protein - physiology
Up-Regulation - genetics
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Summary:Metastasis is a multistep process that involves the deregulation of oncogenes and tumor suppressors beyond changes required for primary tumor formation. RHOB is known to have tumor suppressor activity, and its knockdown is associated with more aggressive tumors as well as changes in cell shape, migration, and adhesion. This study shows that oncogenic microRNA, miR-21, represses RHOB expression by directly targeting the 3' untranslated region. Loss of miR-21 is associated with an elevation of RHOB in hepatocellular carcinoma cell lines Huh-7 and HepG2 and in the metastatic breast cancer cell line MDA-MB-231. Using in vitro models of distinct stages of metastasis, we showed that loss of miR-21 also causes a reduction in migration, invasion, and cell elongation. The reduction in migration and cell elongation can be mimicked by overexpression of RHOB. Furthermore, changes in miR-21 expression lead to alterations in matrix metalloproteinase-9 activity. Therefore, we conclude that miR-21 promotes multiple components of the metastatic phenotype in vitro by regulating several important tumor suppressors, including RHOB.
ISSN:1541-7786
1557-3125
DOI:10.1158/1541-7786.mcr-09-0465