CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m(6)A-modified CREB1 mRNA.
CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m(6)A-modified CREB1 mRNA.
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CircEZH 2/miR-133 b/IGF 2BP 2通过增强m（6）A修饰的CREB 1 mRNA的稳定性来延缓结直肠癌进展
DOI：
10.1186/s12943-022-01608-7
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发表时间：
2022-06-30
期刊：
影响因子：
37.3
通讯作者：
Zhan, Qiang
中科院分区：
文献类型：
--
作者：
Yao, Bing;Zhang, Qinglin;Yang, Zhou;An, Fangmei;Nie, He;Wang, Hui;Yang, Cheng;Sun, Jing;Chen, Ke;Zhou, Jingwan;Bai, Bing;Gu, Shouyong;Zhao, Wei;Zhan, Qiang
环状RNA（circRNA）的异常表达有助于人类恶性肿瘤的发生和发展，但其潜在机制在很大程度上仍不清楚。采用高通量测序技术筛选结直肠癌及癌旁正常组织中异常表达的circRNAs或miRNAs。进行了一系列功能获得和丧失研究以评估CRC细胞的生物学行为。进一步应用RNA pulldown、质谱、RIP、qRT-PCR、Western blot、荧光素酶报告基因分析和MeRIP-seq分析来剖析详细的机制。本研究利用RNA-seq技术在大肠癌组织中筛选出一种新的circRNA，命名为circEZH 2（hsa_circ_0006357），其表达与大肠癌患者的临床病理特征和预后密切相关。在生物学上，circEZH 2在体外和体内促进CRC细胞的增殖和迁移。在机制上，circEZH 2与m6 A阅读器IGF 2BP 2相互作用并阻断其泛素化依赖性降解。同时，circEZH 2可以作为miR-133 b的海绵，导致IGF 2BP 2的上调。特别地，circEZH 2/IGF 2BP 2增强CREB 1 mRNA的稳定性，从而加重CRC进展。我们的研究结果不仅揭示了circEZH 2在调节CRC进展中的关键作用，而且还倡导减弱circEZH 2/miR-133 b/IGF 2BP 2/CREB 1调节轴以对抗CRC。在线版本包含补充材料，可通过10.1186/s12943-022-01608-7获得。
Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive. High-throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer (CRC) and adjacent normal tissues. A series of gain- and loss-of-function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT-PCR, Western blot, luciferase reporter assays and MeRIP-seq analysis were further applied to dissect the detailed mechanisms. Here, a novel circRNA named circEZH2 (hsa_circ_0006357) was screened out by RNA-seq in CRC tissues, whose expression is closely related to the clinicpathological characteristics and prognosis of CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m6A reader IGF2BP2 and blocks its ubiquitination-dependent degradation. Meanwhile, circEZH2 could serve as a sponge of miR-133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2/IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression. Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2/miR-133b/IGF2BP2/ CREB1 regulatory axis to combat CRC. The online version contains supplementary material available at 10.1186/s12943-022-01608-7.
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影响因子：
5
作者：
Greene J;Baird AM;Brady L;Lim M;Gray SG;McDermott R;Finn SP
通讯作者：
Finn SP
影响因子：
64.5
作者：
Bartsch, D;Ghirardi, M;Kandel, ER
通讯作者：
Kandel, ER
DOI：
10.1177/0394632016686985
发表时间：
2017-03
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3.5
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作者：
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Huettelmaier, Stefan
影响因子：
46.9
作者：
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通讯作者：
Sharpless, Norman E.