Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Int J Mol Med. 2013 Sep;32(3):593-8. doi: 10.3892/ijmm.2013.1439. Epub 2013 Jul 12.
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.
耐药性是癌症治疗中化疗失败的主要原因之一。微小 RNA（miRNA 或 miR）是一种短的非编码 RNA 分子，可在后转录水平上调节基因表达，并在多种生物学过程中发挥关键作用。在本研究中，我们报告 miR-503 调节非小细胞肺癌细胞对顺铂的耐药性。与亲本 A549 细胞相比，耐顺铂的非小细胞肺癌细胞 A549/CDDP 中 miR-503 的表达降低。miR-503 的过表达使 A549/CDDP 细胞对顺铂敏感，而 A549 细胞中 miR-503 的抑制增加了对顺铂的耐药性。在机制上，miR-503 特异性靶向 Bcl-2，这是 A549/CDDP 细胞中上调的抗凋亡蛋白。miR-503 的异位表达降低了 Bcl-2 蛋白水平，并使 A549/CDDP 细胞对顺铂诱导的细胞凋亡敏感。总之，我们的结果表明，miR-503 通过靶向 Bcl-2 调节细胞凋亡，从而调节非小细胞肺癌细胞对顺铂的耐药性。
