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Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET

Ovarian cancer is one of the most aggressive female reproductive tract tumors. Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However, ovarian cancers often acquire chemotherapeutic resistance to this agent. We investigated the mechanism of chemoresistance by analysis of microR...

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Autores principales: Mitamura, T, Watari, H, Wang, L, Kanno, H, Hassan, M K, Miyazaki, M, Katoh, Y, Kimura, T, Tanino, M, Nishihara, H, Tanaka, S, Sakuragi, N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641356/
https://www.ncbi.nlm.nih.gov/pubmed/23552883
http://dx.doi.org/10.1038/oncsis.2013.3
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author Mitamura, T
Watari, H
Wang, L
Kanno, H
Hassan, M K
Miyazaki, M
Katoh, Y
Kimura, T
Tanino, M
Nishihara, H
Tanaka, S
Sakuragi, N
author_facet Mitamura, T
Watari, H
Wang, L
Kanno, H
Hassan, M K
Miyazaki, M
Katoh, Y
Kimura, T
Tanino, M
Nishihara, H
Tanaka, S
Sakuragi, N
author_sort Mitamura, T
collection PubMed
description Ovarian cancer is one of the most aggressive female reproductive tract tumors. Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However, ovarian cancers often acquire chemotherapeutic resistance to this agent. We investigated the mechanism of chemoresistance by analysis of microRNAs using the ovarian cancer cell line KFr13 and its PTX-resistant derivative (KFr13Tx). We found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of miR31 re-sensitized them to PTX both in vitro and in vivo. miR-31 was found to bind to the 3′-UTR of mRNA of MET, and the decrease in MET correlated to higher sensitivity to PTX. Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo. In addition, lower levels of miR31 and higher expression of MET in human ovarian cancer specimens were significantly correlated with PTX chemoresistance and poor prognosis. This study demonstrated miR31-dependent regulation of MET for chemoresistance of ovarian cancer, raising the possibility that combination therapy with a MET inhibitor and PTX will increase PTX efficacy.
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spelling pubmed-36413562013-05-02 Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET Mitamura, T Watari, H Wang, L Kanno, H Hassan, M K Miyazaki, M Katoh, Y Kimura, T Tanino, M Nishihara, H Tanaka, S Sakuragi, N Oncogenesis Original Article Ovarian cancer is one of the most aggressive female reproductive tract tumors. Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However, ovarian cancers often acquire chemotherapeutic resistance to this agent. We investigated the mechanism of chemoresistance by analysis of microRNAs using the ovarian cancer cell line KFr13 and its PTX-resistant derivative (KFr13Tx). We found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of miR31 re-sensitized them to PTX both in vitro and in vivo. miR-31 was found to bind to the 3′-UTR of mRNA of MET, and the decrease in MET correlated to higher sensitivity to PTX. Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo. In addition, lower levels of miR31 and higher expression of MET in human ovarian cancer specimens were significantly correlated with PTX chemoresistance and poor prognosis. This study demonstrated miR31-dependent regulation of MET for chemoresistance of ovarian cancer, raising the possibility that combination therapy with a MET inhibitor and PTX will increase PTX efficacy. Nature Publishing Group 2013-03 2013-03-25 /pmc/articles/PMC3641356/ /pubmed/23552883 http://dx.doi.org/10.1038/oncsis.2013.3 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Original Article
Mitamura, T
Watari, H
Wang, L
Kanno, H
Hassan, M K
Miyazaki, M
Katoh, Y
Kimura, T
Tanino, M
Nishihara, H
Tanaka, S
Sakuragi, N
Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET
title Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET
title_full Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET
title_fullStr Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET
title_full_unstemmed Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET
title_short Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET
title_sort downregulation of mirna-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase met
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641356/
https://www.ncbi.nlm.nih.gov/pubmed/23552883
http://dx.doi.org/10.1038/oncsis.2013.3
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