miR-512-5p induces apoptosis and inhibits glycolysis by targeting p21 in non-small cell lung cancer cells
miR-512-5p induces apoptosis and inhibits glycolysis by targeting p21 in non-small cell lung cancer cells
复制标题
DOI：
10.3892/ijo.2015.3279
复制
发表时间：
2016-02-01
影响因子：
5.2
通讯作者：
Zhou, Caicun
中科院分区：
文献类型：
--
作者：
Chu, Kaili;Gao, Guanghui;Zhou, Caicun
MicroRNA是一个小的非编码RNA家族，构成了普遍的基因调控。在这项研究中，我们发现miR-512- 5 p在非小细胞肺癌（NSCLC）患者肿瘤样本中的表达与其配对的正常肺组织相比下调。此外，视黄酸处理还增加了miR-512- 5 p的表达。过表达miR-512- 5 p可诱导NSCLC细胞系A549和H1299凋亡，而miR-512- 5 p抑制剂可逆转稳定表达miR-512的H1299细胞的这种作用。miR-512- 5 p抑制NSCLC细胞中的糖酵解和迁移，但对细胞增殖没有影响。我们确定p21为miR-512- 5 p的靶基因。miR-512- 5 p过表达导致p21蛋白和mRNA水平下降。p21的敲除导致与miR-512- 5 p过表达所观察到的类似的对细胞凋亡和糖酵解的影响，以及在稳定表达miR-512的H1299细胞中挽救miR-512- 5 p抑制剂对细胞凋亡的影响。总之，我们目前的研究表明，miR-512- 5 p能够靶向p21诱导A549和H1299细胞系的凋亡和抑制糖酵解。
MicroRNAs are a family of small non-coding RNAs that constitute a prevalent gene regulation. In this study, we showed the expression of miR-512-5p is downregulated in non-small cell lung cancer (NSCLC) patient tumor samples compared to its paired normal lung tissues. Moreover, expression of miR-512-5p was increased by retinoic acid treatment. Overexpression of miR-512-5p induced apoptosis of NSCLC cell lines A549 and H1299, and miR-512-5p inhibitor reversed this effect in H1299 cells stably expressing miR-512. miR-512-5p inhibited glycolysis and migration in NSCLC cells, but shows no effect on cell proliferation. We identified p21 as a target gene of miR-512-5p. Overexpression of miR-512-5p led to the decrease of p21 protein and mRNA level. Knockdown of p21 resulted in similar effects on apoptosis and glycolysis as that observed of miR-512-5p overexpression, as well as rescued the effect of miR-512-5p inhibitor on cell apoptosis in H1299 cells stably expressing miR-512. In conclusion, our present study revealed miR-512-5p was able to target p21 to induce apoptosis and inhibit glycolysis in A549 and H1299 cell lines.