title: MicroRNA-425-5p regulates chemoresistance in colorectal cancer cells via regulation of Programmed Cell Death 10.
abstract: 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 HCT116 cell lines to identify differentially expressed miRNAs. miRNA 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 HCT116-R compared with parental HCT116 cells. Inhibition of miR-425-5p reversed chemoresistance in HCT116-R cells. Programmed cell death 10 (PDCD10) 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 HCT116-R xenografts to chemo drugs in vivo. Our study demonstrated that miR-425-5p regulates chemoresistance of CRC cells by modulating PDCD10 expression level both in vitro and in vivo. MiR-425-5p may represent a new therapeutic target for the intervention of CRC.
authors.affiliation: Wuxi People's Hospital, Wuxi, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xingqian
authors.initials: X
authors.lastname: Hu
authors.affiliation: Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Miao
authors.affiliation: Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Kuiyu
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Songkui
authors.initials: S
authors.lastname: Cui
authors.affiliation: Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Wuxi People's Hospital, Wuxi, Jiangsu, China.|Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C555677:MIRN425 microRNA, human; D035683:MicroRNAs
keywords: PDCD10; chemoresistance; colorectal cancer; miR-425-5p