An alternative microRNA-mediated post-transcriptional regulation of GADD45A by p53 in human non-small-cell lung cancer cells.
An alternative microRNA-mediated post-transcriptional regulation of GADD45A by p53 in human non-small-cell lung cancer cells.
复制标题
人非小细胞肺癌细胞中 p53 对 GADD45A 的另一种 microRNA 介导的转录后调节
DOI：
10.1038/s41598-017-07332-3
复制
发表时间：
2017-08-02
影响因子：
4.6
通讯作者：
Shao N
中科院分区：
文献类型：
--
作者：
Li J;Dong J;Li S;Xia W;Su X;Qin X;Chen Y;Ding H;Li H;Huang A;Bai C;Hu T;Wang C;Chu B;Shao N
GADD45A（growth arrest and DNA damage inducible alpha）是一种由遗传毒性和非遗传毒性胁迫诱导的应激反应基因，参与多种关键过程，包括细胞周期检查点的控制和DNA修复。GADD 45 A的表达受多种转录因子的直接调节，其中p53是最具代表性的。此外，转录后调节也在GADD 45 A表达中起作用。然而，关于microRNA（miRNAs）对GADD45A表达的调控作用知之甚少。作为一种潜在的肿瘤抑制因子，miR-138在多种癌症中具有多效性的生物学功能。我们之前已经报道了p53介导的miR-138在人非小细胞肺癌（NSCLC）细胞中的激活。在这项研究中，我们发现miR-138特异性靶向AGO2，从而影响miR-130b的稳定性和成熟。miR-130 b表达降低可促进GADD 45 A的表达，并导致人NSCLC细胞G2/M期阻滞和增殖抑制。我们的结果表明，p53可以通过miR-138参与的转录后途径上调人NSCLC细胞中的GADD 45 A。
GADD45A (growth arrest and DNA damage inducible alpha), a stress response gene induced by genotoxic and nongenotoxic stresses, is implicated in various key processes, including the control of cell cycle checkpoints and DNA repair. The expression of GADD45A is directly regulated by numerous transcription factors, with p53 being the most representative. Moreover, post-transcriptional regulation also plays a role in GADD45A expression. However, little is known about the regulatory effects of microRNAs (miRNAs) on GADD45A expression. As a potential tumour suppressor, miR-138 has pleiotropic biological functions in various cancers. We have previously reported p53-mediated activation of miR-138 in human non-small-cell lung cancer (NSCLC) cells. In this study, we found that miR-138 specifically targeted AGO2, which affects the stability and maturation of miR-130b. Decreased expression of miR-130b promoted the expression of GADD45A and resulted in the G2/M phase arrest and proliferation inhibition in human NSCLC cells. Our results suggested that p53 could alternatively upregulate GADD45A in human NSCLC cells through a post-transcriptional pathway in which miR-138 is involved.
登录
查看更多内容
DOI：
10.1126/science.1190809
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cifuentes D;Xue H;Taylor DW;Patnode H;Mishima Y;Cheloufi S;Ma E;Mane S;Hannon GJ;Lawson ND;Wolfe SA;Giraldez AJ
通讯作者：
Giraldez AJ
影响因子：
4
作者：
Kamp, William M.;Wang, Ping-yuan;Hwang, Paul M.
通讯作者：
Hwang, Paul M.
影响因子：
64.5
作者：
Diederichs, Sven;Haber, Daniel A.
通讯作者：
Haber, Daniel A.
影响因子：
13.5
作者：
Cheng, Na;Li, Yandong;Han, Ze-Guang
通讯作者：
Han, Ze-Guang
影响因子：
64.5
作者：
KASTAN, MB;ZHAN, QM;FORNACE, AJ
通讯作者：
FORNACE, AJ