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:10.1038/s41420-022-01151-w

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

Cell Death Discov. 2022 Aug 12;8(1):356. doi: 10.1038/s41420-022-01151-w.

Authors

Haixiang Shen¹, Yufan Ying¹, Xueyou Ma¹, Haiyun Xie¹, Shiming Chen¹, Jiazhu Sun¹, Zixiang Liu¹, Chao Wen¹, Zitong Yang¹, Xiao Wang¹, Mingjie Xu¹, Jindan Luo¹, Ben Liu^{1

2}, Jiangfeng Li³, Xiangyi Zheng^{4

5}, Liping Xie^{6

7}

Affiliations

¹ Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China.
² Cancer Center, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
³ Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. lijf@zju.edu.cn.
⁴ Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. zheng_xy@zju.edu.cn.
⁵ Cancer Center, Zhejiang University, Hangzhou, 310058, Zhejiang, China. zheng_xy@zju.edu.cn.
⁶ Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang, China. xielp@zju.edu.cn.
⁷ Cancer Center, Zhejiang University, Hangzhou, 310058, Zhejiang, China. xielp@zju.edu.cn.

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.

Abstract

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