MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer.
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 cance...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3701631?pdf=render |
| _version_ | 1819183230122721280 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Christine How |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T22:58:43Z |
| format | Article |
| id | doaj.art-6a20b90bdb664c539cc1e742b4a21fdb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T22:58:43Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6a20b90bdb664c539cc1e742b4a21fdb2022-12-21T18:09:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6784610.1371/journal.pone.0067846MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer.Christine HowAngela B Y HuiNehad M AlajezWei ShiPaul C BoutrosBlaise A ClarkeRui YanMelania PintilieAnthony FylesDavid W HedleyRichard P HillMichael MilosevicFei-Fei LiuThe 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.http://europepmc.org/articles/PMC3701631?pdf=render |
| spellingShingle | 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 MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. PLoS ONE |
| title | MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. |
| title_full | MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. |
| title_fullStr | MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. |
| title_full_unstemmed | MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. |
| title_short | MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis in cervical cancer. |
| title_sort | microrna 196b regulates the homeobox b7 vascular endothelial growth factor axis in cervical cancer |
| url | http://europepmc.org/articles/PMC3701631?pdf=render |
| work_keys_str_mv | AT christinehow microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT angelabyhui microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT nehadmalajez microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT weishi microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT paulcboutros microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT blaiseaclarke microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT ruiyan microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT melaniapintilie microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT anthonyfyles microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT davidwhedley microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT richardphill microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT michaelmilosevic microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer AT feifeiliu microrna196bregulatesthehomeoboxb7vascularendothelialgrowthfactoraxisincervicalcancer |