title: MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer.
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.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: How
authors.forename: Angela B Y
authors.initials: AB
authors.lastname: Hui
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Alajez
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
authors.forename: Blaise A
authors.initials: BA
authors.lastname: Clarke
authors.forename: Rui
authors.initials: R
authors.lastname: Yan
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Anthony
authors.initials: A
authors.lastname: Fyles
authors.forename: David W
authors.initials: DW
authors.lastname: Hedley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005720:Gamma Rays / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A