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

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 perfo...

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Detalles Bibliográficos
Autores principales: Yi, Jingkun, Liu, Rucong, Liu, Yu, Guo, Ting, Li, Yang, Zhou, Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690298/
https://www.ncbi.nlm.nih.gov/pubmed/36360248
http://dx.doi.org/10.3390/genes13112011
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author Yi, Jingkun
Liu, Rucong
Liu, Yu
Guo, Ting
Li, Yang
Zhou, Yuan
author_facet Yi, Jingkun
Liu, Rucong
Liu, Yu
Guo, Ting
Li, Yang
Zhou, Yuan
author_sort Yi, Jingkun
collection PubMed
description 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.
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spelling pubmed-96902982022-11-25 Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation Yi, Jingkun Liu, Rucong Liu, Yu Guo, Ting Li, Yang Zhou, Yuan Genes (Basel) Article 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. MDPI 2022-11-02 /pmc/articles/PMC9690298/ /pubmed/36360248 http://dx.doi.org/10.3390/genes13112011 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yi, Jingkun
Liu, Rucong
Liu, Yu
Guo, Ting
Li, Yang
Zhou, Yuan
Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation
title Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation
title_full Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation
title_fullStr Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation
title_full_unstemmed Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation
title_short Integrative Transcriptomic Analysis Identify Potential m6A Pathway-Related Drugs That Inhibit Cancer Cell Proliferation
title_sort integrative transcriptomic analysis identify potential m6a pathway-related drugs that inhibit cancer cell proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690298/
https://www.ncbi.nlm.nih.gov/pubmed/36360248
http://dx.doi.org/10.3390/genes13112011
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