title: STAT5a-targeting miRNA enhances chemosensitivity to cisplatin and 5-fluorouracil             in human colorectal cancer cells.
abstract: Signal transducers and activators of transcription 5 (STAT5) has been shown to be involved in a variety of cellular processes, including survival, proliferation, invasion, angiogenesis and immune evasion and is frequently overexpressed in human solid tumors and blood malignancies. The aim of this study was to investigate the role of STAT5a in colorectal cancer (CRC) progression. We inhibited the expression of STAT5a using lentivirus-mediated artificial microRNA (miRNA) interference in vitro and investigated the viability of CRC cells by CCK-8 assay. We observed the cell viability after treatment with cisplatin (CDDP) or 5-fluorouracil (5-Fu) by CCK-8 assay, and the apoptosis induced by chemotherapy using flow cytometric analysis and Annexin V RFP staining assay. We inhibited the mRNA expression by 54% and the protein expression by 60% of STAT5 by RNA interference targeting STAT5a. Cell viability assays showed that inhibition of STAT5a did not affect the viability of SW1116 cells. However, we found that inhibition of STAT5a restored the sensitivity of SW1116 cells to CDDP and 5-Fu. In additional experiments, we found that inhibition of STAT5a significantly promoted CRC cell apoptosis by CDDP and 5-Fu. In the present study, we found that inhibition of STAT5a promotes apoptosis of CRC cells induced by chemotherapy drugs, such as CDDP or 5-Fu. These results suggest that inhibition of STAT5a may serve as a potential new target for CRC treatment.
authors.affiliation: Department of Respiratory Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Hong
authors.forename: Gongyan
authors.initials: G
authors.lastname: Chen
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Changjie
authors.initials: C
authors.lastname: Lou
authors.forename: Yinling
authors.initials: Y
authors.lastname: Mao
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.forename: Yanqiao
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017304:Annexin A5 / Q000096:biosynthesis / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D016086:Lentivirus; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017304:Annexin A5; D000964:Antimetabolites, Antineoplastic; D035683:MicroRNAs; D012334:RNA, Neoplasm; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins; D002945:Cisplatin; D005472:Fluorouracil