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

Erin C. Connolly, Koenraad Van Doorslaer, Leslie E. Rogler, Charles E. Rogler

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)691-700
Number of pages10
JournalMolecular Cancer Research
Volume8
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Overexpression of miR-21 promotes an in vitro metastatic phenotype by targeting the tumor suppressor RHOB'. Together they form a unique fingerprint.

  • Cite this