Cargando…

MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway

More and more studies indicate the relevance of miRNAs in inducing certain drug resistance. Our study aimed to investigate whether microRNA‐130b‐3p (miR‐130b) mediates the chemoresistance as well as proliferation of lung cancer (LC) cells. MTS assay and apoptosis analysis were conducted to determine...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Qiang, Zhang, Bin, Sun, Leina, Yan, Qingna, Zhang, Yu, Zhang, Zhenfa, Su, Yanjun, Wang, Changli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001533/
https://www.ncbi.nlm.nih.gov/pubmed/29653464
http://dx.doi.org/10.1002/cbf.3331
_version_ 1783332026599866368
author Zhang, Qiang
Zhang, Bin
Sun, Leina
Yan, Qingna
Zhang, Yu
Zhang, Zhenfa
Su, Yanjun
Wang, Changli
author_facet Zhang, Qiang
Zhang, Bin
Sun, Leina
Yan, Qingna
Zhang, Yu
Zhang, Zhenfa
Su, Yanjun
Wang, Changli
author_sort Zhang, Qiang
collection PubMed
description More and more studies indicate the relevance of miRNAs in inducing certain drug resistance. Our study aimed to investigate whether microRNA‐130b‐3p (miR‐130b) mediates the chemoresistance as well as proliferation of lung cancer (LC) cells. MTS assay and apoptosis analysis were conducted to determine cell proliferation and apoptosis, respectively. Binding sites were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT‐PCR and immunoblot, respectively. Mouse xenograft model was used to evaluate the role of miR‐130b in cisplatin resistance in vivo. The rising level of miR‐130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. We identified PTEN as miR‐130b's major target and inversely correlated with miR‐130b expression in LC. Moreover, excessive miR‐130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. Suppression of miR‐130b enhanced drug cytotoxicity and reduced proliferation of A549/CR cells both internally and externally. Particularly, miR‐130b mediated Wnt/β‐catenin signalling pathway activities, chemoresistance and proliferation in LC cell, which was partially blocked following knockdown of PTEN. These findings suggest that miR‐130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/β‐catenin pathway. The rising level of miR‐130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. Moreover, excessive miR‐130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. These findings suggest that miR‐130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/β‐catenin pathway.
format Online
Article
Text
id pubmed-6001533
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-60015332018-06-21 MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway Zhang, Qiang Zhang, Bin Sun, Leina Yan, Qingna Zhang, Yu Zhang, Zhenfa Su, Yanjun Wang, Changli Cell Biochem Funct Research Articles More and more studies indicate the relevance of miRNAs in inducing certain drug resistance. Our study aimed to investigate whether microRNA‐130b‐3p (miR‐130b) mediates the chemoresistance as well as proliferation of lung cancer (LC) cells. MTS assay and apoptosis analysis were conducted to determine cell proliferation and apoptosis, respectively. Binding sites were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT‐PCR and immunoblot, respectively. Mouse xenograft model was used to evaluate the role of miR‐130b in cisplatin resistance in vivo. The rising level of miR‐130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. We identified PTEN as miR‐130b's major target and inversely correlated with miR‐130b expression in LC. Moreover, excessive miR‐130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. Suppression of miR‐130b enhanced drug cytotoxicity and reduced proliferation of A549/CR cells both internally and externally. Particularly, miR‐130b mediated Wnt/β‐catenin signalling pathway activities, chemoresistance and proliferation in LC cell, which was partially blocked following knockdown of PTEN. These findings suggest that miR‐130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/β‐catenin pathway. The rising level of miR‐130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. Moreover, excessive miR‐130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. These findings suggest that miR‐130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/β‐catenin pathway. John Wiley and Sons Inc. 2018-04-13 2018-06 /pmc/articles/PMC6001533/ /pubmed/29653464 http://dx.doi.org/10.1002/cbf.3331 Text en © 2018 The Authors. Cell Biochemistry & Function Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zhang, Qiang
Zhang, Bin
Sun, Leina
Yan, Qingna
Zhang, Yu
Zhang, Zhenfa
Su, Yanjun
Wang, Changli
MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway
title MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway
title_full MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway
title_fullStr MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway
title_full_unstemmed MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway
title_short MicroRNA‐130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/β‐catenin pathway
title_sort microrna‐130b targets pten to induce resistance to cisplatin in lung cancer cells by activating wnt/β‐catenin pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001533/
https://www.ncbi.nlm.nih.gov/pubmed/29653464
http://dx.doi.org/10.1002/cbf.3331
work_keys_str_mv AT zhangqiang microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway
AT zhangbin microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway
AT sunleina microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway
AT yanqingna microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway
AT zhangyu microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway
AT zhangzhenfa microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway
AT suyanjun microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway
AT wangchangli microrna130btargetsptentoinduceresistancetocisplatininlungcancercellsbyactivatingwntbcateninpathway