Cargando…
miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways
MicroRNAs (miRNAs) are attractive therapeutic targets for various therapy-resistant tumors. However, the association between miRNA and BRAF inhibitor resistance in melanoma remains to be elucidated. We used microarray analysis to comprehensively study the miRNA expression profiling of vemurafenib re...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288205/ https://www.ncbi.nlm.nih.gov/pubmed/27448964 http://dx.doi.org/10.18632/oncotarget.10669 |
_version_ | 1782504287634456576 |
---|---|
author | Sun, Xiaoyan Li, Jun Sun, Yanhong Zhang, Yi Dong, Liyun Shen, Chen Yang, Liu Yang, Ming Li, Yan Shen, Guanxin Tu, Yating Tao, Juan |
author_facet | Sun, Xiaoyan Li, Jun Sun, Yanhong Zhang, Yi Dong, Liyun Shen, Chen Yang, Liu Yang, Ming Li, Yan Shen, Guanxin Tu, Yating Tao, Juan |
author_sort | Sun, Xiaoyan |
collection | PubMed |
description | MicroRNAs (miRNAs) are attractive therapeutic targets for various therapy-resistant tumors. However, the association between miRNA and BRAF inhibitor resistance in melanoma remains to be elucidated. We used microarray analysis to comprehensively study the miRNA expression profiling of vemurafenib resistant (VemR) A375 melanoma cells in relation to parental A375 melanoma cells. MicroRNA-7 (miR-7) was identified to be the most significantly down-regulated miRNA in VemR A375 melanoma cells. We also found that miR-7 was down-regulated in Mel-CVR cells (vemurafenib resistant Mel-CV melanoma cells). Reestablishment of miR-7 expression could reverse the resistance of both cells to vemurafenib. We showed that epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R) and CRAF were over-expressed in VemR A375 melanoma cells. Introduction of miR-7 mimics could markedly decrease the expressions of EGFR, IGF-1R and CRAF and further suppressed the activation of MAPK and PI3K/AKT pathway in VemR A375 melanoma cells. Furthermore, tumor growth was inhibited in an in vivo murine VemR A375 melanoma tumor model transfected with miR-7 mimics. Collectively, our study demonstrated that miR-7 could reverse the resistance to BRAF inhibitors in certain vemurafenib resistant melanoma cell lines. It could advance the field and provide the basis for further studies in BRAF inhibitor resistance in melanoma. |
format | Online Article Text |
id | pubmed-5288205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-52882052017-02-07 miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways Sun, Xiaoyan Li, Jun Sun, Yanhong Zhang, Yi Dong, Liyun Shen, Chen Yang, Liu Yang, Ming Li, Yan Shen, Guanxin Tu, Yating Tao, Juan Oncotarget Research Paper MicroRNAs (miRNAs) are attractive therapeutic targets for various therapy-resistant tumors. However, the association between miRNA and BRAF inhibitor resistance in melanoma remains to be elucidated. We used microarray analysis to comprehensively study the miRNA expression profiling of vemurafenib resistant (VemR) A375 melanoma cells in relation to parental A375 melanoma cells. MicroRNA-7 (miR-7) was identified to be the most significantly down-regulated miRNA in VemR A375 melanoma cells. We also found that miR-7 was down-regulated in Mel-CVR cells (vemurafenib resistant Mel-CV melanoma cells). Reestablishment of miR-7 expression could reverse the resistance of both cells to vemurafenib. We showed that epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R) and CRAF were over-expressed in VemR A375 melanoma cells. Introduction of miR-7 mimics could markedly decrease the expressions of EGFR, IGF-1R and CRAF and further suppressed the activation of MAPK and PI3K/AKT pathway in VemR A375 melanoma cells. Furthermore, tumor growth was inhibited in an in vivo murine VemR A375 melanoma tumor model transfected with miR-7 mimics. Collectively, our study demonstrated that miR-7 could reverse the resistance to BRAF inhibitors in certain vemurafenib resistant melanoma cell lines. It could advance the field and provide the basis for further studies in BRAF inhibitor resistance in melanoma. Impact Journals LLC 2016-07-18 /pmc/articles/PMC5288205/ /pubmed/27448964 http://dx.doi.org/10.18632/oncotarget.10669 Text en Copyright: © 2016 Sun et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Sun, Xiaoyan Li, Jun Sun, Yanhong Zhang, Yi Dong, Liyun Shen, Chen Yang, Liu Yang, Ming Li, Yan Shen, Guanxin Tu, Yating Tao, Juan miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways |
title | miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways |
title_full | miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways |
title_fullStr | miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways |
title_full_unstemmed | miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways |
title_short | miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways |
title_sort | mir-7 reverses the resistance to brafi in melanoma by targeting egfr/igf-1r/craf and inhibiting the mapk and pi3k/akt signaling pathways |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288205/ https://www.ncbi.nlm.nih.gov/pubmed/27448964 http://dx.doi.org/10.18632/oncotarget.10669 |
work_keys_str_mv | AT sunxiaoyan mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT lijun mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT sunyanhong mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT zhangyi mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT dongliyun mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT shenchen mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT yangliu mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT yangming mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT liyan mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT shenguanxin mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT tuyating mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways AT taojuan mir7reversestheresistancetobrafiinmelanomabytargetingegfrigf1rcrafandinhibitingthemapkandpi3kaktsignalingpathways |