Cell Death Discovery (Aug 2022)

FTO promotes clear cell renal cell carcinoma progression via upregulation of PDK1 through an m6A dependent pathway

  • Haixiang Shen,
  • Yufan Ying,
  • Xueyou Ma,
  • Haiyun Xie,
  • Shiming Chen,
  • Jiazhu Sun,
  • Zixiang Liu,
  • Chao Wen,
  • Zitong Yang,
  • Xiao Wang,
  • Mingjie Xu,
  • Jindan Luo,
  • Ben Liu,
  • Jiangfeng Li,
  • Xiangyi Zheng,
  • Liping Xie

DOI
https://doi.org/10.1038/s41420-022-01151-w
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 12

Abstract

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Abstract FTO, as an m6A mRNA demethylase, is involved in various cancers. However, the role of FTO in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we discovered FTO is upregulated in ccRCC. Functionally, knockdown of FTO significantly impairs the proliferation and migration ability of ccRCC cells. Mechanistically, our data suggest FTO promotes the proliferation and migration of ccRCC through preventing degradation of PDK1 mRNA induced by YTHDF2 in an m6A-dependent mechanism. Overall, our results identify the protumorigenic role of FTO through the m6A/YTHDF2/PDK1 pathway, which could be a promising therapeutic target for ccRCC.