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

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

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.

Keywords: cancer cell proliferation; connectivity map; drug; m6A methylation; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Cell Proliferation
  • Gene Expression Profiling
  • Humans
  • Methylation
  • Neoplasms* / genetics
  • Transcriptome*

Substances

  • Adenosine

Grants and funding

This study was supported by grants from National Natural Science Foundation of China [32070658] and the Open Project was funded by the Key laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing [2022 Open Project-3].