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miR-1244 通过 MEF2D 表达对顺铂治疗的非小细胞肺癌的影响。

Effect of miR-1244 on cisplatin-treated non-small cell lung cancer via MEF2D expression.

作者信息

Li Guang-Jian, Zhao Guang-Qiang, Yang Jia-Peng, Zhou Yong-Chun, Yang Kai-Yun, Lei Yu-Jie, Huang Yun-Chao

机构信息

Department of Thoracic Surgery, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China.

出版信息

Oncol Rep. 2017 Jun;37(6):3475-3483. doi: 10.3892/or.2017.5624. Epub 2017 May 4.

Abstract

The aim of this study was to investigate the function of miR-1244 in cisplatin-treated non-small cell lung cancer (NSCLC). The results of quantitative PCR analysis revealed that the expression levels of miR-1244 in cisplatin‑treated A549 and NCI-H522 human lung cancer cell lines were lower than those in untreated A549 and NCI-H522 cells. Similarly, the expression level of miR-1244 in NSCLC tissue samples from cisplatin-treated patients was also lower than that in non-cisplatin-treated NSCLC patients. Notably, the overall survival times of cisplatin-treated NSCLC patients with high miR-1244 expression were superior to those patients with low miR-1244 expression. We found that overexpression of miR-1244 suppressed cell viability and increased LDH toxicity in cisplatin-treated A549 and NCI-H522 cells. Additionally, overexpression of miR-1244 induced the apoptosis of cisplatin-treated A549 and NCI-H522 cells. Furthermore, overexpression of miR-1244 promoted caspase-3 activity and p53 and Bax protein expression, and suppressed myocyte enhancer factor 2D (MEF2D) and cyclin D1 protein expression in cisplatin‑treated A549 and NCI-H522 cells. Small interfering RNA (siRNA) targeting MEF2D suppressed the protein expression of MEF2D, and was able to decrease the proliferation, promote caspase-3 activity, p53 and Bax protein expression and inhibit cyclin D1 protein expression in cisplatin-treated A549 and NCI-H522 cells following the overexpression of miR-1244. In summary, we found that miR-1244 affected cisplatin-treated NSCLC via MEF2D expression.

摘要

本研究旨在探讨miR-1244在顺铂治疗的非小细胞肺癌(NSCLC)中的作用。定量PCR分析结果显示,顺铂处理的A549和NCI-H522人肺癌细胞系中miR-1244的表达水平低于未处理的A549和NCI-H522细胞。同样,顺铂治疗患者的NSCLC组织样本中miR-1244的表达水平也低于未接受顺铂治疗的NSCLC患者。值得注意的是,miR-1244高表达的顺铂治疗NSCLC患者的总生存时间优于miR-1244低表达的患者。我们发现,miR-1244的过表达抑制了顺铂处理的A549和NCI-H522细胞的活力,并增加了乳酸脱氢酶毒性。此外,miR-1244的过表达诱导了顺铂处理的A549和NCI-H522细胞的凋亡。此外,miR-1244的过表达促进了顺铂处理的A549和NCI-H522细胞中caspase-3活性以及p53和Bax蛋白表达,并抑制了肌细胞增强因子2D(MEF2D)和细胞周期蛋白D1蛋白表达。靶向MEF2D的小干扰RNA(siRNA)抑制了MEF2D的蛋白表达,并能够在miR-1244过表达后降低顺铂处理的A549和NCI-H522细胞的增殖、促进caspase-3活性、p53和Bax蛋白表达并抑制细胞周期蛋白D1蛋白表达。总之,我们发现miR-1244通过MEF2D表达影响顺铂治疗的NSCLC。

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