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人膀胱癌中N-甲基腺苷甲基化组图谱的全转录组范围图谱

Transcriptome-Wide Map of N-Methyladenosine Methylome Profiling in Human Bladder Cancer.

作者信息

Li Aolin, Gan Ying, Cao Congcong, Ma Binglei, Zhang Quan, Zhang Qian, Yao Lin

机构信息

Department of Urology, Peking University First Hospital, Beijing, China.

Institute of Urology, Peking University, Beijing, China.

出版信息

Front Oncol. 2021 Nov 15;11:717622. doi: 10.3389/fonc.2021.717622. eCollection 2021.

Abstract

N-Methyladenosine (mA) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of mA, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide mA profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, mA is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different mA methylation levels of gene might regulate its expression. In summary, our results for the first time provide an mA landscape of human bladder cancer, which expand the understanding of mA modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through mA modification in bladder cancer.

摘要

N-甲基腺苷(mA)是多种物种中分布最广泛的RNA内部修饰。尽管在研究mA的生物学作用方面取得了最新进展,但其在膀胱癌发生发展中的功能仍不清楚。在本研究中,我们使用MeRIPty-55-seq和RNA-seq方法,获得了膀胱癌及配对的癌旁正常组织全转录组范围的mA图谱和基因表达模式。我们的研究结果表明,与癌旁正常组织相比,膀胱癌组织中有2331个低甲基化mRNA、3819个高甲基化mRNA,32个低甲基化lncRNA、105个高甲基化lncRNA,以及15个低甲基化circRNA、238个高甲基化circRNA。此外,mA最常存在于编码序列(CDS)中,两组之间在起始密码子和终止密码子附近也存在一些差异。功能富集分析显示,差异甲基化的mRNA、lncRNA和circRNA主要富集于癌症中的转录失调和TNF信号通路。我们还发现基因的不同mA甲基化水平可能调控其表达。总之,我们的结果首次提供了人类膀胱癌的mA图谱,拓展了对mA修饰的认识,并揭示了膀胱癌中通过mA修饰对mRNA、lncRNA和circRNA的调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6714/8634328/b8656ab4ac6b/fonc-11-717622-g001.jpg

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