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.
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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
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