Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells
Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells
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抑制长链非编码 RNA HOTAIR 的表达可抑制肾癌细胞的增殖和致瘤性。
DOI：
10.1007/s13277-014-2453-4
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发表时间：
2014-12-01
期刊：
影响因子：
--
通讯作者：
Liu, Te
中科院分区：
文献类型：
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作者：
Wu, Yuanhao;Liu, Junfeng;Liu, Te
尽管已知长链非编码rna （lncRNAs）在多种癌症的细胞调控中发挥重要作用，但其在肾癌细胞中的调控机制尚不清楚。HOX转录反义RNA （HOTAIR）是一种lncRNA，与染色质修饰酶协同调节基因沉默。HOTAIR在几种类型的癌细胞中过表达。因此，我们假设lncRNA HOTAIR对细胞增殖和侵袭至关重要，其敲低可诱导肾癌细胞凋亡。lncRNA HOTAIR在肾癌细胞中表达升高。此外，通过RNA干扰siRNA敲低lncRNA HOTAIR可显著影响G0/G1期细胞周期，并在体外削弱细胞增殖和侵袭能力。异种移植实验证实，沉默lncRNA HOTAIR表达后，肾癌细胞形成的异种移植肿瘤的生长受到抑制。此外，染色质免疫沉淀（ChIP）和rna结合蛋白免疫沉淀（RIP）实验显示，lncRNA HOTAIR敲低导致EZH2和H3K27me3位点与lncRNA HOTAIR的募集和结合能力减弱。此外，通过沉默lncRNA HOTAIR表达和调节共价组蛋白，细胞周期相关基因位点处于活跃转录状态。
Although long non-coding RNAs (lncRNAs) are known to play an important role in cell regulation in several cancers, the regulatory mechanisms in renal carcinoma cells remain unclear. HOX transcript antisense RNA (HOTAIR), an lncRNA, coordinates with chromatin-modifying enzymes to regulate gene silencing. HOTAIR is over-expressed in several types of carcinoma cells. Thus, we hypothesised that lncRNA HOTAIR is crucial for cell proliferation and invasion and that its knockdown induces apoptosis in renal carcinoma cells. lncRNA HOTAIR expression was found to be elevated in renal carcinoma cells. Additionally, lncRNA HOTAIR knockdown by RNA interference with siRNA was found to significantly affect the cell cycle in the G0/G1 phase and weaken the abilities of cell proliferation and invasion in vitro. Xenograft experiments confirmed that the growth of xenograft tumours formed by renal carcinoma cells was suppressed after silencing lncRNA HOTAIR expression. Moreover, chromatin immunoprecipitation (ChIP) and RNA-binding protein immunoprecipitation (RIP) assays revealed that knockdown of lncRNA HOTAIR led to the weakening of the recruitment and binding abilities of EZH2 and H3K27me3 locus with lncRNA HOTAIR. Furthermore, the cell cycle-related gene locus was in an active transcriptional state by the silencing of lncRNA HOTAIR expression and modulation of covalent histones.