title: miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin by targeting Bcl-2.
abstract: Drug resistance is one of the leading causes of chemotherapy failure in cancer treatment. MicroRNAs (miRNAs or miRs) are short non-coding RNA molecules that post-transcriptionally regulate gene expression and play a critical role in diverse biological processes. In this study, we report that miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin. The expression of miR-503 was decreased in the cisplatin-resistant non-small cell lung cancer cells, A549/CDDP, compared with the parental A549 cells. The overexpression of miR-503 sensitized the A549/CDDP cells to cisplatin, whereas the inhibition of miR-503 in the A549 cells increased resistance to cisplatin. Mechanistically, miR-503 specifically targeted Bcl-2, an anti-apoptotic protein upregulated in the A549/CDDP cells. The ectopic expression of miR-503 reduced the Bcl-2 protein level and sensitized the A549/CDDP cells to cisplatin-induced apoptosis. Taken together, our results suggest that miR-503 regulates cell apoptosis, at least in part by targeting Bcl-2, and thus modulates the resistance of non-small cell lung cancer cells to cisplatin.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Qiu
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Tongshan
authors.initials: T
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Chen
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: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C545473:MIRN503 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D002945:Cisplatin