整合转录组分析鉴定出潜在的 m6A 通路相关药物，抑制癌细胞增殖。

Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation.

机构信息

Department of Biomedical Informatics, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University, Beijing 100191, China.

出版信息

Genes (Basel). 2022 Nov 2;13(11):2011. doi: 10.3390/genes13112011.

DOI:10.3390/genes13112011

PMID:36360248

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9690298/

Abstract

Recent studies have found that m6A modification of mRNA may play important roles in the progression of various types of cancers. However, current knowledge about drugs that can interfere with m6A methylation and inhibit cancer cell proliferation is still far from comprehensive. To this end, we performed integrative analysis on transcriptome data with perturbation of m6A writers or erasers and identified consensus m6A-related differentially expressed genes (DEGs). Comparative analysis of these m6A-related DEGs with Connectivity Map signatures highlight potential m6A-targeted drugs. Among them, we experimentally verified the inhibitory effects of AZ628 on the proliferation of human breast cancer cell lines and R428 on the proliferation of human melanoma cell lines. Both drugs can significantly reduce the cellular level of m6A modification. These results suggest an m6A-related new target pathway by AZ628 and R428 and provide new candidate m6A-related drugs that inhibit cancer cell proliferation.

摘要

最近的研究发现，mRNA 的 m6A 修饰可能在各种类型癌症的进展中发挥重要作用。然而，目前关于可以干扰 m6A 甲基化并抑制癌细胞增殖的药物的知识仍然很不全面。为此，我们对 m6A 写入器或擦除器扰动的转录组数据进行了综合分析，并确定了共识 m6A 相关的差异表达基因 (DEGs)。将这些 m6A 相关的 DEGs 与 Connectivity Map 特征进行比较分析，突出了潜在的 m6A 靶向药物。其中，我们通过实验验证了 AZ628 对人乳腺癌细胞系增殖的抑制作用和 R428 对人黑色素瘤细胞系增殖的抑制作用。这两种药物都能显著降低细胞内 m6A 修饰水平。这些结果表明了 AZ628 和 R428 的 m6A 相关新靶途径，并提供了抑制癌细胞增殖的新候选 m6A 相关药物。