title: Upregulation of microRNA-524-5p enhances the cisplatin sensitivity of gastric cancer cells by modulating proliferation and metastasis via targeting SOX9.
abstract: Cisplatin-based chemotherapy is the most commonly used treatment regimen for gastric cancer (GC), however, the resistance to cisplatin represents the key limitation for the therapeutic efficacy. Aberrant expression of MiR-524-5p appears to be involves in tumorigenesis and chemoresistance. However, the mechanism by which miR-524-5p mediates effects of cisplatin treatment in GC remains poorly understood. Expressions of MiR-524-5p was detected in GC tissues and cell lines by qRT-PCR. Cell proliferation was observed by MTT assay; Cell migration was detected by transwell migration and invasion assay. The targeting protein of miR-524-5p was identified by luciferase reporter assay and western blot. We found that downregulation of miR-524-5p in GC tissues and cell lines. SC-M1 and AZ521 cells resistant to cisplatin expressed low levels of miR-524-5p in comparison to the sensitive parental cells. Overexpression of miR-524-5p expression in SC-M1 and AZ521 cells inhibited cell proliferation, migration, and invasion, and conferred sensitivity to cisplatin-resistant GC cells. Subsequently, we identified SOX9 as a functional target protein of miR-524-5p and found that SOX9 overexpression could counteracts the chemosensitizing effects of miR-524-5p. These results provide novel insight into the regulation of GC tumorigenesis and progression by miRNAs. Restoration of miR-524-5p may have therapeutic potential against GC.
authors.affiliation: Department of General Surgery, The Second Hospital Affiliated to Jiaxing University, Jiaxing, 314000, Zhejiang Province, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Hepato-Pancreato-Biliary Surgery, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, 215006, Jiangsu Province, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Hong
authors.affiliation: The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (The State Key Laboratory Incubation Base), Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China.
authors.forename: Mingde
authors.initials: M
authors.lastname: Qin
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (The State Key Laboratory Incubation Base), Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (The State Key Laboratory Incubation Base), Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China.
authors.forename: Hansi
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D034622:RNA Interference; D055758:SOX9 Transcription Factor / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C000599909:MIRN-524 microRNA, human; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D002945:Cisplatin
keywords: MiR-524-5p; SOX9; chemoresistance; gastric cancer; microRNA