Open AccessMicro RNA ‐21 induces 5‐fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD 4
Author(s) -
Wei Xueju,
Wang Weibin,
Wang Lanlan,
Zhang Yuanyuan,
Zhang Xian,
Chen Mingtai,
Wang Fang,
Yu Jia,
Ma Yanni,
Sun Guotao
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.626
Subject(s) - pten , cancer research , pancreatic cancer , microrna , transfection , biology , cell growth , suppressor , cancer , apoptosis , cell culture , gene , pi3k/akt/mtor pathway , biochemistry , genetics
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 ( PATU 8988 and PANC ‐1). We report that PATU 8988 cells resistant to 5‐ FU express high levels of miR‐21 in comparison to sensitive primary PATU 8988 cells. Suppression of miR‐21 expression in 5‐Fu‐resistant PATU 8988 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 PATU 8988 and PANC ‐1 cells. The proresistance effects of miR‐21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD 4 . Overexpression of PTEN and PDCD 4 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 PDCD 4 can rescue 5‐ FU sensitivity and the phenotypic characteristics disrupted by miR‐21.