CircPTPRA blocks the recognition of RNA N(6)-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression.
CircPTPRA blocks the recognition of RNA N(6)-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression.
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CircPTPRA 通过与 IGF2BP1 相互作用阻断 RNA N6-甲基腺苷的识别，从而抑制膀胱癌进展
DOI：
10.1186/s12943-021-01359-x
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发表时间：
2021-04-14
期刊：
影响因子：
37.3
通讯作者：
Jiang G
中科院分区：
文献类型：
--
作者：
Xie F;Huang C;Liu F;Zhang H;Xiao X;Sun J;Zhang X;Jiang G
已发现环状RNA（circRNA）通过各种机制对膀胱癌（BC）的进展具有显著影响。本研究的目的是鉴定新的调控IGF 2BP 1（一个关键的m6 A阅读器）功能的circRNA，并探讨其在BC中的调控机制和临床意义。首先，研究IGF 2BP 1在BC中的临床作用。然后，进行RNA免疫沉淀测序（RIP-seq）分析以鉴定BC细胞中与IGF 2BP 1相互作用的circRNA。在BC细胞系和动物异种移植研究中研究了IGF 2BP 1和候选circPTPRA的总体生物学作用。随后，我们研究了circPTPRA对IGF 2BP 1的调控作用，并通过RNA测序筛选出其靶基因。最后，我们探讨了circPTPRA可能作为m6 A识别阻断剂的潜在分子机制。我们证明IGF 2BP 1主要与BC细胞胞质中的circPTPRA结合。circPTPRA的异位表达可阻断IGF 2BP 1对BC细胞增殖、迁移和侵袭的促进作用。重要的是，circPTPRA通过与IGF 2BP 1相互作用下调IGF 2BP 1对MYC和FSCN 1表达的调节。此外，通过与IGF 2BP 1的KH结构域的相互作用，circPTPRA部分干扰了IGF 2BP 1介导的m6 A修饰的RNA的识别。这项研究确定了外显子环状circPTPRA作为一种新的肿瘤抑制因子，通过内源性阻断IGF 2BP 1对m6 A修饰的RNA的识别来抑制癌症进展，表明circPTPRA可以作为BC患者的可利用的治疗靶点。在线版本包含补充材料，可通过10.1186/s12943-021-01359-x获得。
Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key m6A reader, and explore the regulatory mechanisms and clinical significances in BC. Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of m6A. We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of m6A-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1. This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to m6A-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC. The online version contains supplementary material available at 10.1186/s12943-021-01359-x.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
11.1
作者：
Mahe M;Dufour F;Neyret-Kahn H;Moreno-Vega A;Beraud C;Shi M;Hamaidi I;Sanchez-Quiles V;Krucker C;Dorland-Galliot M;Chapeaublanc E;Nicolle R;Lang H;Pouponnot C;Massfelder T;Radvanyi F;Bernard-Pierrot I
通讯作者：
Bernard-Pierrot I
影响因子：
5.3
作者：
Lemm, I;Ross, J
通讯作者：
Ross, J
影响因子：
64.5
作者：
Meyer KD;Patil DP;Zhou J;Zinoviev A;Skabkin MA;Elemento O;Pestova TV;Qian SB;Jaffrey SR
通讯作者：
Jaffrey SR
影响因子：
2.3
作者：
Li, Yang;Xu, Zhiwen;Zhu, Minghui
通讯作者：
Zhu, Minghui