Kruppel-like factor 9 inhibits glioma cell proliferation and tumorigenicity via downregulation of miR-21
Kruppel-like factor 9 inhibits glioma cell proliferation and tumorigenicity via downregulation of miR-21
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Kruppel 样因子 9 通过下调 miR-21 抑制神经胶质瘤细胞增殖和致瘤性
DOI：
10.1016/j.canlet.2014.10.007
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发表时间：
2015-01-28
期刊：
影响因子：
9.7
通讯作者：
Ke, Yiquan
中科院分区：
文献类型：
--
作者：
Huang, Shuyun;Wang, Chanjuan;Ke, Yiquan
Kruppel样因子（KLF）是一种含锌指的转录因子，在调节分化和发育以及恶性肿瘤发生的生物学过程中发挥关键作用。越来越多的证据表明Kruppel样因子9（KLF 9）在调节肿瘤发生中起着关键作用。然而，KLF 9在胶质瘤进展中的生物学作用和分子机制尚不清楚。在此，我们发现KLF 9表达在胶质瘤中强烈降低。KLF 9表达减少促进胶质瘤细胞增殖。重要的是，KLF 9表达的重建抑制了体内胶质瘤细胞增殖和肿瘤生长。此外，我们确定KLF 9与miR-21启动子相互作用，导致miR-21表达抑制和细胞周期停滞。总之，我们的研究结果表明，KLF功能在肿瘤发生中的新机制，也可能为人类癌症的临床干预提供新的靶点。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Kruppel-like factors (KLFs) are zinc finger-containing transcription factors that play key roles in the regulation of differentiation and development as well as biological processes central to the development of malignancies. Increasing evidence indicates that Kruppel-like factor 9 (KLF9) plays a critical role in regulating tumorigenesis. However, the biological role and molecular mechanism of KLF9 in glioma progression remain unclear. Herein, we found that KLF9 expression was strongly reduced in gliomas. Reduced KLF9 expression promoted glioma cell proliferation. Importantly, re-constitution of KLF9 expression inhibited glioma cell proliferation and tumor growth in vivo. Furthermore, we determined that KLF9 interacted with the miR-21 promoter, leading to suppression of miR-21 expression and cell cycle arrest. Taken together, our findings indicate a novel mechanism for KLF function in tumorigenesis and may also suggest new targets for clinical intervention in human cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.