Respiratory Department, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
Eur Rev Med Pharmacol Sci. 2017 Jun;21(11):2626-2634.
Non-small cell lung cancer (NSCLC), as an ordinary malignant tumor, presents with high death rate and poor prognosis. Few literatures have explored the association between NSCLC development and lncRNAs expression. This study focuses on the important role of a novel lncRNA TRPM2-AS in the development of chemo-resistance in NSCLC.
The expression level of lncRNA TRPM2-AS was identified by using qRT-PCR assay. The apoptosis rate and the alteration of the cell cycle were detected by the flow cytometric analysis. Cell Counting Kit-8 assay (CCK8) was utilized for detecting chemo-sensitivity of the cisplatin-resistant A549/DDP cells. The p53 and p66shc protein levels were detected by Western blotting assay.
A549/DDP cells presented remarkably higher expression of lncRNA TRPM2-AS than paired A549 cells. Moreover, re-sensitization to cisplatin was seen in A549/DDP cells after lncRNA TRPM2-AS knockdown. On the contrary, the sensitivity of lncRNA TRPM2-AS-overexpressed A549 cells to cisplatin decreased obviously when compared with the control. Furthermore, downregulated lncRNA TRPM2-AS induced cell apoptosis and altered cell cycle distribution through activating the p53-p66shc pathway.
We suggest that lncRNA TRPM2-AS participates in the resistance of NSCLC cells to cisplatin, which may provide a new therapeutic target of NSCLC.
非小细胞肺癌（NSCLC）作为一种常见的恶性肿瘤，具有高死亡率和预后不良的特点。很少有文献探讨 NSCLC 发展与 lncRNA 表达之间的关系。本研究重点探讨了新型 lncRNA TRPM2-AS 在 NSCLC 化疗耐药中的重要作用。
通过 qRT-PCR 检测 lncRNA TRPM2-AS 的表达水平。通过流式细胞术分析检测细胞凋亡率和细胞周期的变化。细胞计数试剂盒-8（CCK8）检测顺铂耐药的 A549/DDP 细胞的化疗敏感性。Western blot 检测 p53 和 p66shc 蛋白水平。
A549/DDP 细胞中 lncRNA TRPM2-AS 的表达明显高于配对的 A549 细胞。此外，lncRNA TRPM2-AS 敲低后，A549/DDP 细胞对顺铂的敏感性明显恢复。相反，与对照组相比，lncRNA TRPM2-AS 过表达的 A549 细胞对顺铂的敏感性明显降低。此外，下调 lncRNA TRPM2-AS 通过激活 p53-p66shc 通路诱导细胞凋亡并改变细胞周期分布。
我们认为 lncRNA TRPM2-AS 参与了 NSCLC 细胞对顺铂的耐药性，这可能为 NSCLC 的治疗提供了一个新的靶点。
