Published on Jan. 1, 2019 in Biochim Biophys Acta Gene Regul Mech volume 1862(1).

PubMed ID: 30342176

DOI: S1874-9399(18)30274-8

Abstract:

In ovarian and breast cancers, the actions of the cytokine CSF-1 lead to poorprognosis. CSF-1 expression can be regulated post-transcriptionally. RNA methylationis another layer of posttranscriptional regulation. The methylation of N(1) atom ofadenine (m(1)A) results in a conformational change of RNA which regulatestranslational efficiency. Our study indicates that the m(1)A is also involved in theCSF-1 mRNA decay. The alteration of ALKBH3 expression, an m(1)A demethylase,regulates the CSF-1 mRNA stability. Demethylation of m(1)A by ALKBH3 increases thehalf-life of CSF-1 mRNA without affecting the translation efficiency. The m(1)A inCSF-1 mRNA is mapped in the 5'UTR near the translation initiation site. YTHDF2, aknown m(6)A reader which interacts with the CCR4-NOT deadenylation complex, is notthe reader of m(1)A-containing CSF-1 mRNA. Overexpression of ALKBH3 increases CSF-1expression and the degree of cancer cell invasiveness without affecting cellproliferation or migration. Collectively, we showed that CSF-1 mRNA decay can beregulated at an epigenetic level, and that alteration of the N(1)‑methylation statusleads to phenotypic changes in cancer cell behavior.CI - Copyright © 2018 Elsevier B.V. All rights reserved.