N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2

Gene. 2020 Jan 5;722:144076. doi: 10.1016/j.gene.2019.144076. Epub 2019 Aug 24.

Abstract

N6-methyladenosine (m6A) is the most prevalent internal modification in mammalian mRNAs and methyltransferase-like 3 (METTL3) is a vital methyltransferase in m6A modification. Here, this study tries to discover the regulatory role of METTL3 and its mechanism in the breast cancer tumorigenesis. Results found that METTL3 was up-regulated in the breast cancer tissue and cells. In vivo and vitro, METTL3 knockdown could decrease the methylation level, reduce the proliferation, accelerate the apoptosis and inhibited the tumor growth. Moreover, we found that Bcl-2 acted as the target of METTL3, thereby regulating the proliferation and apoptosis of breast cancer. This study could reveal the potential mechanism of m6A modification in the breast cancer tumorigenesis, providing potential drug targets in the treatment.

Keywords: Bcl-2; Breast cancer; METTL3; N6-methyladenosine; m6A.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Apoptosis
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Humans
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • N-methyladenosine
  • Methyltransferases
  • METTL3 protein, human
  • Adenosine