Published on Oct. 1, 2019 in Transl Oncol volume 12(10).

PubMed ID: 31352195

DOI: 10.1016/j.tranon.2019.06.007

Abstract:

BACKGROUND: Gene expression can be posttranscriptionally regulated by a complexnetwork of proteins. N1-methyladenosine (m1A) is a newly validated RNA modification.However, little is known about both its influence and biogenesis in tumordevelopment. METHODS: This study analyzed TCGA data of patients with five kinds ofgastrointestinal (GI) cancers. Using data from cBioPortal, molecular features of thenine known m1A-related enzymes in GI cancers were investigated. Using a variety ofbioinformatics approach, the impact of m1A regulators on its downstream signalingpathway was studied. To further confirm this regulation, the effect of m1A writerALKBH3 knockdown was studied using RNA-seq data from published database. RESULTS:Dysregulation and multiple types of genetic alteration of putative m1A-relatedenzymes in tumor samples were observed. The ErbB and mTOR pathways with ErbB2, mTOR,and AKT1S1 hub genes were identified as being regulated by m1A-related enzymes. Theexpression of both ErbB2 and AKT1S1 was decreased after m1A writer ALKBH3 knockdown.Furthermore, Gene Ontology analysis revealed that m1A downstream genes wereassociated with cell proliferation, and the results showed that m1A genes arereliably linked to mTOR. CONCLUSION: This study demonstrated for the first time thedysregulation of m1A regulators in GI cancer and its signaling pathways and willcontribute to the understanding of RNA modification in cancer.CI - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.