title: Involvement of miR-143 in cisplatin resistance of gastric cancer cells via targeting IGF1R and BCL2.
abstract: We investigated the possible role of miR-143 in the development of cisplatin resistance in human gastric cancer cell line. miR-143 was detected by quantitative real-time PCR. Cisplatin resistance changes of cells was tested via MTT assay. Target genes of miR-143 were verified by dual-luciferase activity assay. Immunohistochemistry, immunofluorescence staining, Western blot, cell proliferation, and clonogenic and apoptosis assay were used to elucidate the mechanism of miR-143 in cisplatin resistance formation. miR-143 was downregulated in gastric cancer tissues and cell lines. It was also downregulated in cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP), which was concurrent with the upregulation of IGF1R and BCL2, compared with the parental SGC7901 cell line, respectively. Overexpressed miR-143 sensitized SGC7901/DDP cells to cisplatin. The luciferase activity suggested that IGF1R and BCL2 were both target genes of miR-143. Enforced miR-143 reduced its target proteins, inhibited SGC7901/DDP cells proliferation, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Our findings suggested that hsa-miR-143 could modulate cisplatin resistance of human gastric cancer cell line at least in part by targeting IGF1R and BCL2.
authors.affiliation: Department of Oncology, Clinical Medical College of Yangzhou University, No. 98 Nantong Western Road, Yangzhou, 225001, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhuang
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
authors.forename: Xiuwei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Ding
authors.forename: Liuqun
authors.initials: L
authors.lastname: Shan
authors.forename: Xia
authors.initials: X
authors.lastname: Shan
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Qian
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Zebo
authors.initials: Z
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Yin
authors.initials: Y
authors.lastname: Ding
authors.forename: Wenfang
authors.initials: W
authors.lastname: Cheng
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: C000597236:IGF1R protein, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1; D002945:Cisplatin