miR-106b-5p targets tumor suppressor gene SETD2 to inactive its function in clear cell renal cell carcinoma.
miR-106b-5p targets tumor suppressor gene SETD2 to inactive its function in clear cell renal cell carcinoma.
复制标题
miR-106b-5p 靶向肿瘤抑制基因 SETD2，使其在透明细胞肾细胞癌中的功能失活。
DOI：
10.18632/oncotarget.2926
复制
发表时间：
2015-02-28
期刊：
影响因子：
--
通讯作者：
Jiang G
中科院分区：
文献类型：
--
作者：
Xiang W;He J;Huang C;Chen L;Tao D;Wu X;Wang M;Luo G;Xiao X;Zeng F;Jiang G
人SET结构域2蛋白（SETD2）失活是透明细胞肾细胞癌（ccRCC）的常见事件。然而，SETD2功能丧失的潜在机制，特别是转录后调控机制仍不清楚。在本研究中，我们发现SETD2在ccRCC组织和细胞系中下调，并与miR-106b-5p的高表达呈负相关。过表达miR-106b-5p导致ccRCC细胞中SETD2 mRNA和蛋白水平降低。在SETD2 3 ' -UTR荧光素酶报告系统中，miR-106b-5p下调了荧光素酶活性，通过突变预测的miR-106b-5p结合位点来消除这种影响。此外，在ccRCC细胞中，miR-106b-5p的衰减诱导细胞周期阻滞在G0/G1期，抑制细胞增殖，增强caspase-3的加工，促进细胞凋亡，而这些作用在敲低SETD2后被逆转。此外，转染miR-106b-5p antagomir可使H3K36me3与p53启动子的结合增加并增强其活性，上调p53的mRNA和蛋白水平，同时转染si-SETD2也可消除这种作用。总的来说，我们的研究结果扩展了对miRNA在转录后水平上对SETD2的调控以及SETD2下游在ccRCC中的调控机制的认识。
Inactivation of human SET domain containing protein 2 (SETD2) is a common event in clear cell renal cell carcinoma (ccRCC). However, the mechanism underlying loss of SETD2 function, particularly the post-transcriptional regulatory mechanism, still remains unclear. In the present study, we found that SETD2 was downregulated and inversely correlated with high expression of miR-106b-5p in ccRCC tissues and cell lines. Over-expression of miR-106b-5p resulted in the decreased mRNA and protein levels of SETD2 in ccRCC cells. In an SETD2 3′-UTR luciferase reporter system, miR-106b-5p downregulated the luciferase activity, and the effects were abolished by mutating the predicted miR-106b-5p binding site. Moreover, attenuation of miR-106b-5p induced cell cycle arrest at G0/G1 phase, suppressed cell proliferation, enhanced processing of caspase-3, and promoted cell apoptosis in ccRCC cells, whereas these effects were reversed upon knockdown of SETD2. In addition, transfection of miR-106b-5p antagomir resulted in the increased binding of H3K36me3 to the promoter of p53 and enhanced its activity, as well as upregulated the mRNA and protein levels of p53, and the effects were also abolished by cotransfection with si-SETD2. Collectively, our findings extend the knowledge about the regulation of SETD2 at the posttranscriptional level by miRNA and regulatory mechanism downstream of SETD2 in ccRCC.
登录
查看更多内容
影响因子：
7.7
作者：
Carvalho S;Vítor AC;Sridhara SC;Martins FB;Raposo AC;Desterro JM;Ferreira J;de Almeida SF
通讯作者：
de Almeida SF
DOI：
10.1158/1078-0432.ccr-12-3886
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hakimi AA;Ostrovnaya I;Reva B;Schultz N;Chen YB;Gonen M;Liu H;Takeda S;Voss MH;Tickoo SK;Reuter VE;Russo P;Cheng EH;Sander C;Motzer RJ;Hsieh JJ;ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
通讯作者：
ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.8
作者：
Al Sarakbi W;Sasi W;Jiang WG;Roberts T;Newbold RF;Mokbel K
通讯作者：
Mokbel K
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM