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结直肠癌中长非编码 RNA 的 N1-甲基腺苷谱分析。

N1-methyladenosine profiling of long non-coding RNA in colorectal cancer.

机构信息

Department of Ultrasound, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

出版信息

IUBMB Life. 2021 Oct;73(10):1235-1243. doi: 10.1002/iub.2534. Epub 2021 Aug 2.

Abstract

N1-methyladenosine (m1A), is a unique methyl group that confers post-transcriptional modification of gene expression, and plays important roles in various human diseases. However, the abundance of this modification and its effects on long non-coding RNAs (lncRNAs) in human colorectal cancer (CRC) remain unclear. In this study, methylated RNA immunoprecipitation sequencing was performed in three pairs of human CRC and nontumorous tissues to identify m1A peaks and its correlation with differential alterations of lncRNA expression in CRC. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathway analyses were applied to predict the potential roles of m1A on gene expression. We found that CRC and adjacent tissues had a noticeable difference in m1A distribution. Notably, HGGAGRA and WGGANGA were recognized as the most significantly enriched motifs, respectively. Co-analysis of methylation and RNA sequencing demonstrated downregulated lncRNAs along with m1A modification in CRC. GO and KEGG pathway analyses revealed that the unique distribution of m1A sites in lncRNAs had a significant correlation with CRC signaling pathways. In conclusion, our results delineated the distribution pattern of m1A methylation on lncRNAs, and provided potential roles of this modification in different pathways and tumor progression of CRC.

摘要

N1-甲基腺苷(m1A)是一种独特的甲基基团,可对基因表达进行转录后修饰,在各种人类疾病中发挥重要作用。然而,这种修饰在人类结直肠癌(CRC)中的丰度及其对长非编码 RNA(lncRNA)的影响尚不清楚。在这项研究中,对三对人 CRC 和非肿瘤组织进行了甲基化 RNA 免疫沉淀测序,以鉴定 m1A 峰及其与 CRC 中 lncRNA 表达差异改变的相关性。基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集途径分析被应用于预测 m1A 对基因表达的潜在作用。我们发现 CRC 和相邻组织中的 m1A 分布有明显差异。值得注意的是,HGGAGRA 和 WGGANGA 分别被认为是最显著富集的基序。m1A 修饰和 RNA 测序的共分析表明,CRC 中存在下调的 lncRNA。GO 和 KEGG 途径分析表明,lncRNA 中 m1A 位点的独特分布与 CRC 信号通路有显著相关性。总之,我们的研究结果描绘了 m1A 甲基化在 lncRNA 上的分布模式,并为该修饰在不同途径和 CRC 肿瘤进展中的潜在作用提供了依据。

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