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

Biochim Biophys Acta Gene Regul Mech. 2019 Jan;1862(1):35-46. doi: 10.1016/j.bbagrm.2018.10.008. Epub 2018 Oct 17.


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.

Keywords: ALKBH3; Breast cancer; CSF-1 mRNA; Ovarian cancer; RNA stability; m(1)A demethylation.

MeSH terms

  • AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase / physiology*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Demethylation
  • Epigenomics
  • Female
  • Humans
  • Macrophage Colony-Stimulating Factor / genetics*
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / pathology*
  • RNA Stability*


  • CSF1 protein, human
  • Macrophage Colony-Stimulating Factor
  • ALKBH3 protein, human
  • AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase