Long noncoding RNA GAS5 promotes bladder cancer cells apoptosis through inhibiting EZH2 transcription.
Long noncoding RNA GAS5 promotes bladder cancer cells apoptosis through inhibiting EZH2 transcription.
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长非编码RNA GAS5通过抑制EZH2转录促进膀胱癌细胞凋亡。
DOI：
10.1038/s41419-018-0264-z
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发表时间：
2018-02-14
影响因子：
9
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Wang M;Guo C;Wang L;Luo G;Huang C;Li Y;Liu D;Zeng F;Jiang G;Xiao X
在最近的研究中发现膀胱癌细胞中长链非编码RNA GAS 5的异常表达。然而，GAS 5在BC发展中的调节功能和潜在的分子机制仍不清楚。在此，我们证实GAS 5水平与膀胱肿瘤临床分期呈负相关。在功能上，GAS 5的过表达降低了T24和EJ膀胱癌细胞的细胞活力并诱导细胞凋亡。GAS 5通过直接与E2 F4相互作用并将E2 F4募集到EZH 2启动子上而有效地抑制EZH 2的转录。我们以前报道过miR-101通过抑制EZH 2的表达诱导BC细胞凋亡。有趣的是，本研究表明GAS 5下调EZH 2导致T24和EJ细胞中miR-101过表达。此外，GAS 5的水平增加的治疗下的藤黄酸（GA），一个有前途的天然抗癌化合物，而敲低GAS 5抑制GA对细胞活力的抑制作用，并取消GA诱导的T24和EJ细胞凋亡。综上所述，我们的研究结果证明了GAS 5通过在转录水平上抑制EZH 2而具有肿瘤抑制作用，并且另外提供了用于治疗人类膀胱癌的新的治疗策略。
Aberrant expression of long noncoding RNA GAS5 in bladder cancer (BC) cells was identified in recent studies. However, the regulatory functions and underlying molecular mechanisms of GAS5 in BC development remain unclear. Here, we confirmed that there was a negative correlation between GAS5 level and bladder tumor clinical stage. Functionally, overexpression of GAS5 reduced cell viability and induced cell apoptosis in T24 and EJ bladder cancer cells. Mechanistically, GAS5 effectively repressed EZH2 transcription by directly interacting with E2F4 and recruiting E2F4 to EZH2 promoter. We previously reported that miR-101 induced the apoptosis of BC cells by inhibiting the expression of EZH2. Interestingly, the present study showed that downregulation of EZH2 by GAS5 resulted in overexpression of miR-101 in T24 and EJ cells. Furthermore, the level of GAS5 was increased under the treatment of Gambogic acid (GA), a promising natural anti-cancer compound, whereas knockdown of GAS5 suppressed the inhibitory effect of GA on cell viability and abolished GA-induced apoptosis in T24 and EJ cells. Taken together, our findings demonstrated a tumor-suppressor role of GAS5 by inhibiting EZH2 on transcriptional level, and additionally provided a novel therapeutic strategy for treating human bladder cancer.
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影响因子：
8
作者：
Parisi, T.;Bronson, R. T.;Lees, J. A.
通讯作者：
Lees, J. A.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbagen.2014.08.019
发表时间：
2014-12-01
影响因子：
3
作者：
Ishaq, Mohammad;Khan, Mohammad Aslam;Majumdar, Sekhar
通讯作者：
Majumdar, Sekhar
影响因子：
--
作者：
Christofides A;Karantanos T;Bardhan K;Boussiotis VA
通讯作者：
Boussiotis VA
影响因子：
16
作者：
Kottakis F;Polytarchou C;Foltopoulou P;Sanidas I;Kampranis SC;Tsichlis PN
通讯作者：
Tsichlis PN