1. Academic Validation
  2. A1CF-promoted colony formation and proliferation of RCC depends on DKK1-MEK/ERK signal axis

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.
Dongsheng Ni 1 Qiying Yi 2 Jianing Liu 1 Yanxia Hu 1 Tao Lv 3 Guo Tan 4 Yamin Liu 1 Lei Xu 1 Hua Xia 1 Qin Zhou 1 Yajun Xie 5
Affiliations

Affiliations

  • 1 The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
  • 2 The animal center, Chongqing Medical University, Chongqing 400016, China.
  • 3 College of Biological Resource and Food Engineering, Center for Yunnan, Qujing Normal University, Qujing, Yunnan 655011, China.
  • 4 Department of Foreign Language, Minzu University of China, Beijing 100081, China.
  • 5 The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. Electronic address: yjxie@cqmu.edu.cn.
Abstract

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.

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