Open AccessN6‐methyladenosine demethylase FTO suppresses clear cell renal cell carcinoma through a novel FTO ‐ PGC ‐1α signalling axis
Author(s) -
Zhuang Changshui,
Zhuang Chengle,
Luo Xiaomin,
Huang Xinbo,
Yao Lv,
Li Jianfa,
Li Yawen,
Xiong Tiefu,
Ye Jing,
Zhang Fangting,
Gui Yaoting
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14128
Subject(s) - demethylase , n6 methyladenosine , cell , cancer research , chemistry , cell growth , oxidative stress , clear cell renal cell carcinoma , methylation , downregulation and upregulation , microbiology and biotechnology , renal cell carcinoma , biology , gene , medicine , epigenetics , methyltransferase , biochemistry
The abundant and reversible N6‐methyladenosine (m6A) R NA modification and its modulators have important roles in regulating various gene expression and biological processes. Here, we demonstrate that fat mass and obesity associated ( FTO ), as an m6A demethylase, plays a critical anti‐tumorigenic role in clear cell renal cell carcinoma (cc RCC ). FTO is suppressed in cc RCC tissue. The low expression of FTO in human cc RCC correlates with increased tumour severity and poor patient survival. The Von Hippel‐Lindau‐deficient cells expressing FTO restores mitochondrial activity, induces oxidative stress and ROS production and shows impaired tumour growth, through increasing expression of PGC ‐1α by reducing m6A levels in its mRNA transcripts. Our work demonstrates the functional importance of the m6A methylation and its modulator, and uncovers a critical FTO ‐ PGC ‐1α axis for developing effective therapeutic strategies in the treatment of cc RCC .