MicroRNA-196b Regulates the Homeobox B7-vascular Endothelial Growth Factor Axis in Cervical Cancer

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jul 18

PMID 23861821

Citations 34

Authors

Christine How

Angela B Y Hui

Nehad M Alajez

Wei Shi

Paul C Boutros

Blaise A Clarke

Rui Yan

Melania Pintilie

Anthony Fyles

David W Hedley

Richard P Hill

Michael Milosevic

Fei-Fei Liu

Affiliations

Soon will be listed here.

Abstract

The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.

Citing Articles

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