MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4

Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR‐21 induces drug resistance to 5‐fluorouracil (5‐FU) in human pancreatic cancer cells (PATU8988 and PANC‐1). We report tha...

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Main Authors:	Wei, Xueju, Wang, Weibin, Wang, Lanlan, Zhang, Yuanyuan, Zhang, Xian, Chen, Mingtai, Wang, Fang, Yu, Jia, Ma, Yanni, Sun, Guotao
Format:	Online
Language:	English
Published:	John Wiley and Sons Inc. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831288/

id	pubmed-4831288
recordtype	oai_dc
spelling	pubmed-48312882016-04-20 MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4 Wei, Xueju Wang, Weibin Wang, Lanlan Zhang, Yuanyuan Zhang, Xian Chen, Mingtai Wang, Fang Yu, Jia Ma, Yanni Sun, Guotao Cancer Biology Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR‐21 induces drug resistance to 5‐fluorouracil (5‐FU) in human pancreatic cancer cells (PATU8988 and PANC‐1). We report that PATU8988 cells resistant to 5‐FU express high levels of miR‐21 in comparison to sensitive primary PATU8988 cells. Suppression of miR‐21 expression in 5‐Fu‐resistant PATU8988 cells can alleviate its 5‐FU resistance. Meanwhile, lentiviral vector‐mediated overexpression of miR‐21 not only conferred resistance to 5‐FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC‐1 cells. The proresistance effects of miR‐21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR‐21‐induced resistance to 5‐FU and migration activity. Our work demonstrates that miR‐21 can confer drug resistance to 5‐FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR‐21, PTEN and PDCD4 can rescue 5‐FU sensitivity and the phenotypic characteristics disrupted by miR‐21. John Wiley and Sons Inc. 2016-02-10 /pmc/articles/PMC4831288/ /pubmed/26864640 http://dx.doi.org/10.1002/cam4.626 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wei, Xueju Wang, Weibin Wang, Lanlan Zhang, Yuanyuan Zhang, Xian Chen, Mingtai Wang, Fang Yu, Jia Ma, Yanni Sun, Guotao
spellingShingle	Wei, Xueju Wang, Weibin Wang, Lanlan Zhang, Yuanyuan Zhang, Xian Chen, Mingtai Wang, Fang Yu, Jia Ma, Yanni Sun, Guotao MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4
author_facet	Wei, Xueju Wang, Weibin Wang, Lanlan Zhang, Yuanyuan Zhang, Xian Chen, Mingtai Wang, Fang Yu, Jia Ma, Yanni Sun, Guotao
author_sort	Wei, Xueju
title	MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4
title_short	MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4
title_full	MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4
title_fullStr	MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4
title_full_unstemmed	MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4
title_sort	microrna‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating pten and pdcd4
description	Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR‐21 induces drug resistance to 5‐fluorouracil (5‐FU) in human pancreatic cancer cells (PATU8988 and PANC‐1). We report that PATU8988 cells resistant to 5‐FU express high levels of miR‐21 in comparison to sensitive primary PATU8988 cells. Suppression of miR‐21 expression in 5‐Fu‐resistant PATU8988 cells can alleviate its 5‐FU resistance. Meanwhile, lentiviral vector‐mediated overexpression of miR‐21 not only conferred resistance to 5‐FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC‐1 cells. The proresistance effects of miR‐21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR‐21‐induced resistance to 5‐FU and migration activity. Our work demonstrates that miR‐21 can confer drug resistance to 5‐FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR‐21, PTEN and PDCD4 can rescue 5‐FU sensitivity and the phenotypic characteristics disrupted by miR‐21.
publisher	John Wiley and Sons Inc.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831288/
_version_	1613566162290868224

MicroRNA‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4

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