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.
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Abbreviations
- miRNAs:
-
MicroRNAs
- DDP:
-
Cisplatin
- MTT:
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
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The authors are grateful to the fund support by the National Natural Science Foundation of China (Grant number 81201705) and the Natural Science Foundation of Jiangsu Province (Grant number BK2012442).
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Ming Zhuang and Qin Shi contributed equally to this work.
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Zhuang, M., Shi, Q., Zhang, X. et al. Involvement of miR-143 in cisplatin resistance of gastric cancer cells via targeting IGF1R and BCL2. Tumor Biol. 36, 2737–2745 (2015). https://doi.org/10.1007/s13277-014-2898-5
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DOI: https://doi.org/10.1007/s13277-014-2898-5