Open AccessMicro RNA ‐425‐5p regulates chemoresistance in colorectal cancer cells via regulation of Programmed Cell Death 10
Author(s) -
Zhang Ye,
Hu Xingqian,
Miao Xiaofei,
Zhu Kuiyu,
Cui Songkui,
Meng Qingyang,
Sun Jialin,
Wang Tong
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12742
Subject(s) - microrna , in vivo , carcinogenesis , cancer research , colorectal cancer , cancer , transfection , cell culture , biology , cancer cell , programmed cell death , microarray analysis techniques , western blot , cell , microbiology and biotechnology , chemistry , gene expression , apoptosis , gene , biochemistry , genetics
Acquired chemoresistance represents a major obstacle in cancer treatment, the underlying mechanism of which is complex and not well understood. MiR‐425‐5p has been reported to be implicated tumorigenesis in a few cancer types. However, its role in regulating chemoresistance has not been investigated in colorectal cancer ( CRC ) cells. Microarray analysis was performed in isogenic chemosensitive and chemoresistant HCT 116 cell lines to identify differentially expressed mi RNA s. mi RNA quantitative real‐time PCR was used to detect miR‐425‐5p expression levels between drug resistant and parental cancer cells. MiR‐425‐5p mimic and inhibitor were transfected, followed by CellTiter‐Glo ® assay to examine drug sensitivity in these two cell lines. Western Blot and luciferase assay were performed to investigate the direct target of miR‐425‐5p. Xenograft mouse models were used to examine in vivo function of miR‐425‐5p. Our data showed that expression of miR‐425‐5p was significantly up‐regulated in HCT 116‐R compared with parental HCT 116 cells. Inhibition of miR‐425‐5p reversed chemoresistance in HCT 116‐R cells. Programmed cell death 10 ( PDCD 10) is the direct target of miR‐425‐5p which is required for the regulatory role of miR‐425‐5p in chemoresistance. MiR‐425‐5p inhibitor sensitized HCT 116‐R xenografts to chemo drugs in vivo . Our study demonstrated that miR‐425‐5p regulates chemoresistance of CRC cells by modulating PDCD 10 expression level both in vitro and in vivo . MiR‐425‐5p may represent a new therapeutic target for the intervention of CRC .