Involvement of miR-143 in cisplatin resistance of gastric cancer cells via targeting IGF1R and BCL2
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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.
KeywordsmiR-143 Cisplatin resistance IGF1R BCL2
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).
Conflicts of interest
- 19.Tanida S, Mizoshita T, Ozeki K, Tsukamoto H, Kamiya T, Kataoka H, et al. Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity: potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment. Int J Surg Oncol. 2012;2012, 862879.PubMedPubMedCentralGoogle Scholar
- 20.Eckstein N, Servan K, Hildebrandt B, Politz A, von Jonquières G, Wolf-Kummeth S, et al. Hyperactivation of the insulin-like growth factor receptor I signaling pathway is an essential event for cisplatin resistance of ovarian cancer cells. Cancer Res. 2009;69(7):2996–3003.CrossRefPubMedGoogle Scholar