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人胎素对人结肠癌细胞系 HCT116 中 mRNA m6A 修饰和表达的影响。

Effect of Humantenine on mRNA m6A Modification and Expression in Human Colon Cancer Cell Line HCT116.

机构信息

Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China.

Department of Pathogen Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China.

出版信息

Genes (Basel). 2022 Apr 27;13(5):781. doi: 10.3390/genes13050781.

DOI:10.3390/genes13050781
PMID:35627166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9140730/
Abstract

Humantenine, an alkaloid isolated from the medicinal herb (Gardner & Chapm.) Benth., has been reported to induce intestinal irritation, but the underlying toxicological mechanisms remain unclear. The object of the present study was to investigate the RNA N6-methyladenosine (m6A) modification and distinct mRNA transcriptome profiles in humantenine-treated HCT116 human colon cancer cells. High-throughput MeRIP-seq and mRNA-seq were performed, and bioinformatic analysis was performed to reveal the role of abnormal RNA m6A modification and mRNA expression in humantenine-induced intestinal cell toxicity. After humantenine treatment of HCT116 cells, 1401 genes were in the overlap of differentially m6A-modified mRNA and differentially expressed mRNA. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology annotation terms for actin cytoskeleton, tight junctions, and adherens junctions were enriched. A total of 11 kinds of RNA m6A methylation regulators were differentially expressed. The m6A methylation levels of target genes were disordered in the humantenine group. In conclusion, this study suggested that the HCT116 cell injury induced by humantenine was associated with the abnormal mRNA expression of m6A regulators, as well as disordered m6A methylation levels of target genes.

摘要

汉藤碱是从药用植物（Gardner & Chapm.）Benth. 中分离得到的一种生物碱，已报道其可诱导肠道炎症，但潜在的毒理学机制尚不清楚。本研究的目的是研究汉藤碱处理的 HCT116 人结肠癌细胞中的 RNA N6-甲基腺苷（m6A）修饰和独特的 mRNA 转录组谱。进行了高通量 MeRIP-seq 和 mRNA-seq，并进行了生物信息学分析，以揭示异常 RNA m6A 修饰和 mRNA 表达在汉藤碱诱导的肠道细胞毒性中的作用。汉藤碱处理 HCT116 细胞后，有 1401 个基因在差异 m6A 修饰 mRNA 和差异表达 mRNA 的重叠中。肌动蛋白细胞骨架、紧密连接和黏着连接的京都基因与基因组百科全书和基因本体论注释术语富集。共有 11 种 RNA m6A 甲基化调节剂差异表达。汉藤碱组中靶基因的 m6A 甲基化水平紊乱。总之，本研究表明汉藤碱诱导的 HCT116 细胞损伤与 m6A 调节剂的异常 mRNA 表达以及靶基因的 m6A 甲基化水平紊乱有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/6536fca11d68/genes-13-00781-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/27d4186317d8/genes-13-00781-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/9b467c399c21/genes-13-00781-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/edc405ee7261/genes-13-00781-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/e76c414d202a/genes-13-00781-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/52aa463408f4/genes-13-00781-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/6536fca11d68/genes-13-00781-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/27d4186317d8/genes-13-00781-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/10403fd003c9/genes-13-00781-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/29af688cad4b/genes-13-00781-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/3d67a08c36a6/genes-13-00781-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/fcfe023facb9/genes-13-00781-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/9b467c399c21/genes-13-00781-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/edc405ee7261/genes-13-00781-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/e76c414d202a/genes-13-00781-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/52aa463408f4/genes-13-00781-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dddf/9140730/6536fca11d68/genes-13-00781-g010.jpg

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