Transcription of HOTAIR is regulated by RhoC-MRTF-A-SRF signaling pathway in human breast cancer cells
Transcription of HOTAIR is regulated by RhoC-MRTF-A-SRF signaling pathway in human breast cancer cells
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DOI：
10.1016/j.cellsig.2017.01.003
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发表时间：
2017-02-01
影响因子：
4.8
通讯作者：
Zhang, Tong-Cun
中科院分区：
文献类型：
--
作者：
He, Hongpeng;Wei, Zhaoqiang;Zhang, Tong-Cun
HOTAIR是一种长链非编码RNA，在癌症组织中高度表达，是一种不良预后因素，而HOTAIR在癌症中表达上调的机制尚不清楚。本研究探讨了HOTAIR在乳腺癌细胞MCF7和T47D中的转录调控。我们发现，当RhoC-ROCK信号通路受到特定sirna或化学抑制剂的干扰时，HOTAIR的表达会下调。进一步发现MRTF-A和SRF影响HOTAIR的表达。HOTAIR启动子活性被证明是由RhoC-MRTF-A-SRF信号以carg -box依赖的方式调节的。此外，MRTF-A被鉴定为与HOTAIR启动子物理相互作用，并且MRTF-A的过表达增强了HOTAIR启动子上RNA聚合酶II的关联。综上所述，我们的研究结果表明，HOTAIR在乳腺癌细胞中受RhoC-MRTF-A-SRF信号通路的调控。(C) 2017年Elsevier Inc.出版。
HOTAIR is a long non-coding RNA highly expressed in cancer tissues and is a negative prognostic factor, whereas the mechanism by which HOTAIR expression is upregulated in cancers remains elusive. In the present study, the regulation of HOTAIR transcription was investigated in breast cancer cells MCF7 and T47D. We found that, when the RhoC-ROCK signaling was disturbed by specific siRNAs or chemical inhibitors, the expression of HOTAIR would be down-regulated. Further, MRTF-A and SRF were found to affect HOTAIR expression. HOTAIR promoter activity was demonstrated to be regulated by the RhoC-MRTF-A-SRF signaling in a CArG-box-dependent manner. Moreover, MRTF-A was identified to physically interact with HOTAIR promoter, and RNA polymerase II association on HOTAIR promoter was enhanced by MRTF-A overexpression. Taken together, our results suggest that HOTAIR is regulated by the RhoC-MRTF-A-SRF signaling pathway in breast cancer cells. (C) 2017 Published by Elsevier Inc.