MicroRNA-34a is an important component of PRIMA-1-induced apoptotic network in human lung cancer cells.
MicroRNA-34a is an important component of PRIMA-1-induced apoptotic network in human lung cancer cells.
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DOI：
10.1002/ijc.25049
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发表时间：
2010-07-15
影响因子：
6.4
通讯作者：
Villalona-Calero, Miguel A.
中科院分区：
文献类型：
--
作者：
Duan, Wenrui;Gao, Li;Wu, Xin;Wang, Li;Nana-Sinkam, Serge P.;Otterson, Gregory A.;Villalona-Calero, Miguel A.
在肿瘤细胞中恢复p53功能将是肺癌治疗的一个有吸引力的策略，因为在超过50%的肺癌中发现了p53突变。小分子PRIMA-1已显示恢复p53的肿瘤抑制功能并诱导人肿瘤细胞的凋亡。PRIMA-1诱导细胞凋亡的机制尚不清楚。我们使用含有突变型（H211和H1155）、野生型（A549）或无效型（H1299）p53的人肺癌细胞系，通过Western免疫印迹分析、TaqMan microRNA实时PCR、细胞活力分析和流式细胞术研究PRIMA-1在凋亡中的作用。PRIMA-1诱导H211和H1155细胞大量凋亡，但对A549和H1299细胞毒性较小。Western免疫印迹分析显示，在用PRIMA-1处理后，PARP在H211和H1155细胞中裂解，但在A549和H1299细胞中不裂解。此外，H211和H1155细胞中p53蛋白也被磷酸化。TaqMan microRNA检测结果显示，处理后的H211和H1155细胞中microRNA-34 a的表达增加。敲低microRNA-34 a可降低PRIMA-1引起的细胞凋亡率。上述结果表明，microRNA-34 a是PRIMA-1诱导的含有突变型p53的癌细胞凋亡网络的重要组成部分之一。
Restoration of p53 function in tumor cells would be an attractive strategy for lung cancer therapy because p53 mutations are found in more than 50% of lung cancers. The small molecule PRIMA-1 has been shown to restore the tumor suppression function of p53 and to induce apoptosis in human tumor cells. The mechanism of apoptosis induced by PRIMA-1 remains unclear. We investigated the effects of PRIMA-1 in apoptosis with Western immunoblot analysis, TaqMan microRNA real-time PCR, cell viability analysis and flow cytometry using human lung cancer cell lines containing mutant (H211 and H1155), wild-type (A549) or null (H1299) p53. PRIMA-1 induced massive apoptosis in the H211 and H1155 cells, but was less toxic to the A549 and H1299 cells. Western immunoblot analysis showed cleavage of PARP in H211 and H1155 cells but not in A549 and H1299 cells following treatment with PRIMA-1. In addition, p53 protein was also phosphorylated in H211 and H1155 cells. TaqMan microRNA assay showed that the expression of microRNA-34a was increased in the H211 and H1155 cells posttreatment. Knockdown microRNA-34a decreased the rate of apoptosis caused by PRIMA-1. The above results suggest that microRNA-34a is one of the important components of PRIMA-1-induced apoptotic network in the cancer cells harboring mutant p53.
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影响因子：
56.9
作者：
CHO, YJ;GORINA, S;PAVLETICH, NP
通讯作者：
PAVLETICH, NP
影响因子：
3.9
作者：
Olivier, M;Eeles, R;Hainaut, P
通讯作者：
Hainaut, P
影响因子：
3
作者：
Duan, Wenrui;Gao, Li;Villalona-Calero, Miguel A.
通讯作者：
Villalona-Calero, Miguel A.
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
DOI：
10.1073/pnas.0800650105
发表时间：
2008-07-01
影响因子：
11.1
作者：
Kong, Yi Wen;Cannell, Ian G.;Bushell, Martin
通讯作者：
Bushell, Martin