SRSF7对m6A的特异性调控促进了胶质母细胞瘤的进展

IF 11.5 2区 生物学 Q1 GENETICS & HEREDITY
Genomics, Proteomics & Bioinformatics Pub Date : 2023-08-01 Epub Date: 2021-12-23 DOI:10.1016/j.gpb.2021.11.001
Yixian Cun, Sanqi An, Haiqing Zheng, Jing Lan, Wenfang Chen, Wanjun Luo, Chengguo Yao, Xincheng Li, Xiang Huang, Xiang Sun, Zehong Wu, Yameng Hu, Ziwen Li, Shuxia Zhang, Geyan Wu, Meisongzhu Yang, Miaoling Tang, Ruyuan Yu, Xinyi Liao, Guicheng Gao, Wei Zhao, Jinkai Wang, Jun Li
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引用次数: 0

摘要

丝氨酸/精氨酸丰富的剪接因子7(SRSF7)是一种已知的剪接因子,已被发现在多种癌症中发挥致癌作用。然而,其致癌作用的机制尚未得到很好的研究。在这里,基于对不同细胞系的 N6-甲基腺苷(m6A)共甲基化网络分析,我们发现 SRSF7 的基因表达与胶质母细胞瘤(GBM)细胞特异性 m6A 甲基化呈正相关。我们随后指出,SRSF7 是一种新型 m6A 调节因子,它通过招募甲基转移酶复合物,特异性地促进其结合位点附近参与细胞增殖和迁移的 mRNA 上的 m6A 甲基化。此外,SRSF7 促进 GBM 细胞的增殖和迁移主要依赖于 m6A 甲基转移酶的存在。PDZ结合激酶(PBK)mRNA上的两个m6A位点受SRSF7调控,并通过胰岛素样生长因子2 mRNA结合蛋白2(IGF2BP2)的识别,部分介导SRSF7在GBM细胞中的作用。总之,我们的发现揭示了 SRSF7 在调控 m6A 中的新作用,并验证了 RNA 结合蛋白(RBPs)介导的 m6A 时空特异性调控的存在及其功能重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. We then indicate that SRSF7 is a novel m6A regulator, which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase. The two m6A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal- and spatial-specific regulation of m6A mediated by RNA-binding proteins (RBPs).

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来源期刊
Genomics, Proteomics & Bioinformatics
Genomics, Proteomics & Bioinformatics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
14.30
自引率
4.20%
发文量
844
审稿时长
61 days
期刊介绍: Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.
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