miR-511 and miR-1297 inhibit human lung adenocarcinoma cell proliferation by targeting oncogene TRIB2.
miR-511 and miR-1297 inhibit human lung adenocarcinoma cell proliferation by targeting oncogene TRIB2.
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miR-511 和 miR-1297 通过靶向癌基因 TRIB2 抑制人肺腺癌细胞增殖
DOI：
10.1371/journal.pone.0046090
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xie SY
中科院分区：
文献类型：
--
作者：
Zhang C;Chi YL;Wang PY;Wang YQ;Zhang YX;Deng J;Lv CJ;Xie SY
微小RNA（miRNAs）是一类小型非编码RNA，它们调控基因并与多种人类疾病（包括癌症）相关。基于微小RNA分析软件对TRIB2癌基因预测的结合位点，对两种微小RNA（miR - 511和miR - 1297）在腺癌中可能的作用进行了研究，并构建了pcDNA - GFP - TRIB2 - 3′UTR载体以研究TRIB2与miR - 511/1297在腺癌细胞系A549中的相互作用。在A549细胞与miR - 511（或miR - 1297）以及pcDNA - GFP - TRIB2 - 3′UTR载体共转染后，通过荧光显微镜和流式细胞术评估绿色荧光蛋白（GFP）的表达。与阴性对照（NC）微小RNA处理的细胞相比，miR - 511和miR - 1297处理的细胞中GFP的表达显著下调。通过蛋白质印迹法进一步检测到在miR - 511（或miR - 1297）处理后TRIB2表达降低。MTT试验显示miR - 511和miR - 1297处理的细胞中A549细胞增殖受到抑制，膜联蛋白V - FITC/PI双染显示与阴性对照培养物相比，这些细胞凋亡增加。TRIB2下游的一个转录因子，CCAAT/增强子结合蛋白α（C/EBPα），在miR - 511（或miR - 1297）降低TRIB2表达后表达水平升高。我们的研究结果表明，miR - 511和miR - 1297作为肿瘤抑制基因，可通过抑制TRIB2并进一步增加C/EBPα的表达，在体外和体内抑制A549细胞的增殖。
microRNAs (miRNAs) are small noncoding RNAs that regulate genes and contribute to many kinds of human diseases, including cancer. Two miRNAs, miR-511 and miR-1297, were investigated for a possible role in adenocarcinoma based on predicted binding sites for the TRIB2 oncogene by microRNA analysis software, and the pcDNA-GFP-TRIB2–3′UTR vector was constructed to investigate the interaction between TRIB2 and miR-511/1297 in the adenocarcinoma cell line A549. Green fluorescent protein (GFP) expression was estimated by fluorescence microscopy and flow cytometry after A549 cells were co-transfected with miR-511 (or miR-1297) and pcDNA-GFP-TRIB2–3′UTR vector. The expression of GFP in the miR-511- and miR-1297-treated cells was significantly downregulated in contrast with the negative-control (NC) miRNA-treated cells. The decreased expression of TRIB2 was further detected after miR-511 (or miR-1297) treatment by western blotting. The MTT test showed inhibition of A549 cell proliferation and Annexin V-FITC/PI dual staining showed increased apoptosis in the miR-511- and miR-1297-treated cells compared to the NC cultures. A transcription factor downstream of TRIB2, the CCAAT/enhancer-binding protein alpha (C/EBPα), was expression at higher levels after miR-511 (or miR-1297) decreasing TRIB2 expression. Our results illustrate that miR-511 and miR-1297 act as tumor suppressor genes, which could suppress A549 cell proliferation in vitro and in vivo by suppressing TRIB2 and further increasing C/EBPα expression.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
8.8
作者：
Kojima, S.;Chiyomaru, T.;Kawakami, K.;Yoshino, H.;Enokida, H.;Nohata, N.;Fuse, M.;Ichikawa, T.;Naya, Y.;Nakagawa, M.;Seki, N.
通讯作者：
Seki, N.
通过抗 miR-150 载体消退 A549 肺癌肿瘤。
影响因子：
4.2
作者：
Li, You-Jie;Zhang, Yan-Xa;Xie, Shu-Yang
通讯作者：
Xie, Shu-Yang
影响因子：
20.3
作者：
D'Alo, F;Johansen, LM;Tenen, DG
通讯作者：
Tenen, DG
影响因子：
4
作者：
Johnson, PF
通讯作者：
Johnson, PF