Human ALKBH3-induced mA demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells
AffiliationUniversity of Arizona Cancer Center
MetadataShow full item record
PublisherELSEVIER SCIENCE BV
CitationWoo, H. H., & Chambers, S. K. (2019). Human ALKBH3-induced m1A demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 1862(1), 35-46.
Rights© 2018 Elsevier B.V. All rights reserved.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractIn ovarian and breast cancers, the actions of the cytokine CSF-1 lead to poor prognosis. CSF-1 expression can be regulated post-transcriptionally. RNA methylation is another layer of posttranscriptional regulation. The methylation of N1 atom of adenine (m1A) results in a conformational change of RNA which regulates translational efficiency. Our study indicates that the m1A is also involved in the CSF-1 mRNA decay. The alteration of ALKBH3 expression, an m1A demethylase, regulates the CSF-1 mRNA stability. Demethylation of m1A by ALKBH3 increases the half-life of CSF-1 mRNA without affecting the translation efficiency. The m1A in CSF-1 mRNA is mapped in the 5'UTR near the translation initiation site. YTHDF2, a known m6A reader which interacts with the CCR4-NOT deadenylation complex, is not the reader of m1A-containing CSF-1 mRNA. Overexpression of ALKBH3 increases CSF-1 expression and the degree of cancer cell invasiveness without affecting cell proliferation or migration. Collectively, we showed that CSF-1 mRNA decay can be regulated at an epigenetic level, and that alteration of the N1‑methylation status leads to phenotypic changes in cancer cell behavior.
Note12 month embargo; Available online 17 October 2018
VersionFinal accepted manuscript
SponsorsWomen's Cancers of the University of Arizona Cancer Center; Bobbi Olson Endowment Fund