Published on Feb. 5, 2020 in Mol Ther volume 28(2).

PubMed ID: 31839484

DOI: S1525-0016(19)30512-X

Abstract:

Epigenetic alterations contributed to human carcinogenesis immensely.N6-methyladenosine (m6A) is one of the most preventive and abundant modifications onRNA molecules present in eukaryotes. However, the biological function of m6Amethylation in colorectal cancer (CRC) remains largely unclear. Here, we found thatMETTL14 was downregulated in CRC tissues and cell lines, and closely correlated withoverall survival (OS). METTL14 knockdown significantly reduced m6A levels in totalRNAs and promoted CRC cell growth and metastasis, whereas METTL14 overexpressionmarkedly increased m6A levels in total RNA and inhibited CRC cell growth andmetastasis. Furthermore, we demonstrated that miR-375 was a downstream target ofMETTL14. We also verified that METTL14 suppressed CRC cell growth via themiR-375/Yes-associated protein 1 (YAP1) pathway, as well as inhibited CRC cellmigration and invasion through the miR-375/SP1 pathway. Taken together, our studiesshowed an important role for METTL14 in CRC progression and provided novel insightinto m6A modification in CRC progression.CI - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.