Human ALKBH3-induced m1A demethylation increases the CSF-1 mRNA stability in breast and ovarian cancer cells

Ho Hyung Woo, Setsuko K. Chambers

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

In 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.

Original languageEnglish (US)
Pages (from-to)35-46
Number of pages12
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1862
Issue number1
DOIs
StatePublished - Jan 2019

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Keywords

  • ALKBH3
  • Breast cancer
  • CSF-1 mRNA
  • Ovarian cancer
  • RNA stability
  • mA demethylation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

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