A1CF-promoted colony formation and proliferation of RCC depends on DKK1-MEK/ERK signal axis

Gene. 2020 Mar 10;730:144299. doi: 10.1016/j.gene.2019.144299. Epub 2019 Dec 24.


The function and mechanism of RNA editing proteins have been extensively studied, but its association with cellular processes and signaling pathways remained unaddressed. Here, we explored the function of RNA editing complementary protein- Apobec-1 Complementation Factor (A1CF) in the proliferation and colony formation of renal cell carcinoma (RCC) cells. Decreased A1CF expression inhibits the proliferation and colony formation of 786-O cells; and further signaling pathway screening demonstrated that A1CF increases ERK activation and DKK1 expression. Moreover, knockdown of DKK1 has similar phenotypes with A1CF deficiency in 786-O cells on cell proliferation and colony formation and ERK activation. Decreasing of DKK1 expression reduces the phosphorylation of ERK1/2 and MEK1/2 increased by A1CF overexpression; further, inhibiting of the phosphorylation of MEK1/2 by U0126 also decreases the ERK activation upregulated by A1CF overexpression. Deficiency of DKK1 or U0126 treatment suppresses the cell proliferation promoted by A1CF overexpression in 786-O cells; furthermore, U0126 treatment inhibits DKK1-increased cell proliferation in 786-O cells. Our results reveal that DKK1 mediates A1CF to activate ERK in promotion renal carcinoma cell proliferation and colony formation. For the important function of ERK signaling pathway in tumor metastasis and key position of DKK1 in Wnt signaling pathway, we associate RNA editing protein-A1CF with multiple cellular processes and signaling pathways through DKK1, and the key node of A1CF-DKK1-MEK/ERK axis is a potential targeting site for RCC therapy.

Keywords: A1CF; DKK1; ERK1/2; MEK1/2; Renal cell carcinoma.

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • MAP Kinase Signaling System / genetics
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Neoplastic Stem Cells / metabolism
  • Phosphorylation
  • RNA Editing / genetics
  • RNA Editing / physiology
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Wnt Signaling Pathway


  • A1CF protein, human
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • RNA-Binding Proteins
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 3