期刊
JOURNAL OF TRANSLATIONAL MEDICINE
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12967-015-0488-y
关键词
DNA (cytosine-5)-methyltransferase 1(DNMT1); Cisplatin resistance; MicroRNA-148b; A549 cell; SPC-A1 cell
Background: The emergence of drug resistance in cancer patients limits the success rate of clinical chemotherapy. MicroRNAs (miRNAs) may play a role in chemoresistance and may be involved in modulating of some drug resistance-related pathways in cancer cells. In this study, the involvement of microRNA-148b (miR-148b) and its roles in the development of chemoresistance in lung cancer are determined. Methods: This study was performed in two lung cancer cell lines (A549 and SPC-A1). The levels of miR-148b and DNMT1 mRNA expression were determined by using Quantitative Real-Time PCR. Proteins of DNMTs are represented by western blot assay. Cell viability was assessed by MTT assay. Cell apoptosis was evaluated using flow cytometry. Results: The data showed a down-regulated of miR-148b expression and evaluated methyltransferases (DNMTs) expression in cisplatin-resisted human non-small cell lung cancer (NSCLC) cell line-A549/DDP and SPC-A1/DDP compared with their parental A549 and SPC-A1 cell line. In transfection experiments, miR-148b mimics reduced the DNMT1 expression, as well as enhanced the sensitivity of cells to cisplatin and cisplatin-induced apoptosis in A549/DDP or SPC-A1/DDP cells. While miR-148b inhibitor increased DNMT1 expression, as well as attenuated the sensitivity of cells to cisplatin in A549 and SPC-A1 cells. miR-148b was showed to exert negative effect on DNMT1 expression by targeting its 3'UTR in A549/DDP and A549 cells. Importantly, silenced DNMT1 increases cisplatin sensitivity of A549/DDP cells and over-expressed DNMT1 reverses pro-apoptosis effect of miR-148b mimic. Conclusions: miR-148b reverses cisplatin-resistance in non-small cell cancer cells via negatively regulating DNMT1 expression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据