METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer

J Cell Mol Med. 2021 Jul;25(14):6602-6617. doi: 10.1111/jcmm.16664. Epub 2021 Jun 2.


N6-methyladenosine (m6A) is a well-known modification of RNA. However, as a key m6A methyltransferase, METTL16 has not been thoroughly studied in gastric cancer (GC). Here, the biological role of METTL16 in GC and its underlying mechanism was studied. Immunohistochemistry was used to detect the expression of METTL16 and relationship between METTL16 level and prognosis of GC was analysed. CCK8, colony formation assay, EdU assay and xenograft mouse model were used to study the effect of METTL16. Regulatory mechanism of METTL16 in the progression of GC was studied through flow cytometry analysis, RNA degradation assay, methyltransferase inhibition assay, RT-qPCR and Western blotting. METTL16 was highly expressed in GC cells and tissues and was associated with prognosis. In vitro and in vivo experiments confirmed that METTL16 promoted proliferation of GC cells and tumour growth. Furthermore, down-regulation of METTL16 inhibited proliferation by G1/S blocking. Significantly, we identified cyclin D1 as a downstream effector of METTL16. Knock-down METTL16 decreased the overall level of m6A and the stability of cyclin D1 mRNA in GC cells. Meanwhile, inhibition of methyltransferase activity reduced the level of cyclin D1. METTL16-mediated m6A methylation promotes proliferation of GC cells through enhancing cyclin D1 expression.

Keywords: METTL16; cyclin D1; gastric cancer; m6A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / genetics
  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cyclin D1 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Male
  • Methylation
  • Methyltransferases / genetics*
  • Mice
  • Middle Aged
  • Prognosis
  • RNA Stability / genetics
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology


  • Cyclin D1
  • METTL16 protein, human
  • Methyltransferases
  • Adenosine