Activation of miR-21 by STAT3 induces proliferation and suppresses apoptosis in nasopharyngeal carcinoma by targeting PTEN gene.
Activation of miR-21 by STAT3 induces proliferation and suppresses apoptosis in nasopharyngeal carcinoma by targeting PTEN gene.
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STAT3激活miR-21通过靶向PTEN基因诱导鼻咽癌增殖并抑制细胞凋亡
DOI：
10.1371/journal.pone.0109929
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kang M
中科院分区：
文献类型：
--
作者：
Ou H;Li Y;Kang M
本研究旨在探讨microRNA-21(miR-21)在鼻咽癌中的作用及miR-21调控PTEN的机制。收集42例鼻咽癌患者和12例健康对照的鼻咽癌组织标本54例。人鼻咽癌细胞株CNE-1、CNE-2、TW03和C666-1用于细胞分析。采用RT-PCR方法检测miR-21基因的表达。用RT-PCR、Western blotting和免疫组织化学方法检测STAT3mRNA和蛋白的表达。为检测miR-21对体外培养的鼻咽癌细胞生长和凋亡的影响，采用CNE1和CNE2细胞株的转染和流式细胞仪检测。TUNEL法检测DNA片段化程度。为了验证miR-21是否能直接识别PTEN基因的3‘-UTRs，采用了荧光素酶报告基因分析方法。与对照组相比，鼻咽癌组织中MIR-21的表达增加，鼻咽癌细胞系中MIR-21的表达也增加。值得注意的是，miR-21的高表达与临床分期和淋巴结转移直接相关。由IL-6激活的转录因子STAT3在转化的鼻咽癌细胞系中直接激活miR-21。此外，miR-21显著抑制PTEN抑癌基因，导致AKT活性增加。体外和体内实验均显示miR-21促进鼻咽癌细胞增殖，抑制细胞凋亡。被STAT3激活的MIR-21通过靶向PTEN-AKT通路诱导鼻咽癌细胞增殖和抑制细胞凋亡。
The present study is to investigate the role of microRNA-21 (miR-21) in nasopharyngeal carcinoma (NPC) and the mechanisms of regulation of PTEN by miR-21. Fifty-four tissue samples were collected from 42 patients with NPC and 12 healthy controls. Human NPC cell lines CNE-1, CNE-2, TWO3 and C666-1 were used for cell assays. To investigate the expression of miR-21, RT-PCR was employed. RT-PCR, Western blotting, and immunohistochemistry were used to measure the expression of STAT3 mRNA and STAT3 protein. To test the effect of miR-21 on the cell growth and apoptosis of NPC cells in vitro, transfection of CNE1 and CNE2 cell lines and flow cytometry were performed. TUNEL assay was used to detect DNA fragmentation. To validate whether miR-21 directly recognizes the 3′-UTRs of PTEN mRNA, luciferase reporter assay was employed. miR-21 expression was increased in NPC tissues compared with control and the same result was found in NPC cell lines. Notably, increased expression of miR-21 was directly related to advanced clinical stage and lymph node metastasis. STAT3, a transcription factor activated by IL-6, directly activated miR-21 in transformed NPC cell lines. Furthermore, miR-21 markedly inhibited PTEN tumor suppressor, leading to increased AKT activity. Both in vitro and in vivo assays revealed that miR-21 enhanced NPC cell proliferation and suppressed apoptosis. miR-21, activated by STAT3, induced proliferation and suppressed apoptosis in NPC by targeting PTEN-AKT pathway.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
14.9
作者：
Knouf EC;Garg K;Arroyo JD;Correa Y;Sarkar D;Parkin RK;Wurz K;O'Briant KC;Godwin AK;Urban ND;Ruzzo WL;Gentleman R;Drescher CW;Swisher EM;Tewari M
通讯作者：
Tewari M
影响因子：
6
作者：
Kurose, K;Zhou, XP;Eng, C
通讯作者：
Eng, C
影响因子：
11.2
作者：
Dai, Bingbing;Meng, Jieru;Roth, Jack A.
通讯作者：
Roth, Jack A.
影响因子：
4.7
作者：
Alder, Hansjuerg;Taccioli, Cristian;Fong, Louise Y. Y.
通讯作者：
Fong, Louise Y. Y.