The long non-coding RNA FOXD2-AS1 promotes bladder cancer progression and recurrence through a positive feedback loop with Akt and E2F1.
The long non-coding RNA FOXD2-AS1 promotes bladder cancer progression and recurrence through a positive feedback loop with Akt and E2F1.
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长非编码 RNA FOXD2-AS1 通过与 Akt 和 E2F1 的正反馈环促进膀胱癌进展和复发
DOI：
10.1038/s41419-018-0275-9
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发表时间：
2018-02-14
影响因子：
9
通讯作者：
Jiang C
中科院分区：
文献类型：
--
作者：
Su F;He W;Chen C;Liu M;Liu H;Xue F;Bi J;Xu D;Zhao Y;Huang J;Lin T;Jiang C
长的非编码RNA(LncRNAs)已被确定为癌症进展中的重要调节因子。LncRNAs和转录因子之间的正反馈环已引起越来越多的关注。AKT通路在膀胱癌的生长和复发中起着至关重要的作用。在本研究中，我们展示了一种涉及FOXD2-AS1、Akt和E2F1的新的调控模式。FOXD2-AS1在膀胱癌中高表达，与肿瘤分期、复发及预后不良有关。进一步的实验表明FOXD2-AS1在体内外均能促进膀胱癌细胞的增殖、迁移和侵袭。基因芯片分析表明，FOXD2-AS1负性调控Akt的负调控因子TRIB3的表达。在机制上，FOXD2-AS1与TRIB3的启动子形成RNADNA复合体，其转录活性随后被抑制，并导致Akt的激活，从而进一步增加参与G/S转换的重要转录因子E2F1的表达。有趣的是，E2F1可以与FOXD2-AS1启动子区域结合，从而增强其转录活性，表明FOXD2-AS1/Akt/E2F1形成了一个反馈环。综上所述，这种正反馈的调节模式可能是膀胱癌治疗的新靶点，FOXD2-AS1有可能成为新的复发预测因子。
Long non-coding RNAs (lncRNAs) have been identified as significant regulators in cancer progression. Positive feedback loops between lncRNAs and transcription factors have attracted increasing attention. Akt pathway plays a crucial role in bladder cancer growth and recurrence. In the present study, we demonstrate a novel regulatory pattern involving FOXD2-AS1, Akt, and E2F1. FOXD2-AS1 is highly expressed in bladder cancer and is associated with tumor stage, recurrence, and poor prognosis. Further experiments showed that FOXD2-AS1 promotes bladder cancer cell proliferation, migration, and invasion in vitro and in vivo. Microarray analysis demonstrated that FOXD2-AS1 negatively regulates the expression of Tribbles pseudokinase 3 (TRIB3), a negative regulator of Akt. Mechanistically, FOXD2-AS1 forms an RNA-DNA complex with the promoter of TRIB3, the transcriptional activity of which is subsequently repressed, and leads to the activation of Akt, which further increases the expression of E2F1, a vital transcription factor involved in the G/S transition. Interestingly, E2F1 could bind to the FOXD2-AS1 promoter region and subsequently enhance its transcriptional activity, indicating that FOXD2-AS1/Akt/E2F1 forms a feedback loop. In summary, this regulatory pattern of positive feedback may be a novel target for the treatment of bladder cancer and FOXD2-AS1 has the potential to be a new recurrence predictor.
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影响因子：
11.1
作者：
Bonasio R;Shiekhattar R
通讯作者：
Shiekhattar R
影响因子：
15.9
作者：
Goehe, Rachel Wilson;Shultz, Jacqueline C.;Chalfant, Charles E.
通讯作者：
Chalfant, Charles E.
DOI：
10.1126/science.1240925
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carpenter S;Aiello D;Atianand MK;Ricci EP;Gandhi P;Hall LL;Byron M;Monks B;Henry-Bezy M;Lawrence JB;O'Neill LA;Moore MJ;Caffrey DR;Fitzgerald KA
通讯作者：
Fitzgerald KA
影响因子：
37.3
作者：
Feldstein O;Nizri T;Doniger T;Jacob J;Rechavi G;Ginsberg D
通讯作者：
Ginsberg D
影响因子：
11.2
作者：
Reichert, Maximilian;Saur, Dieter;Schneider, Guenter
通讯作者：
Schneider, Guenter