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이혜민Hyemin Lee
University of Texas MD Anderson Cancer Center
J. Clin. Invest., Apr 15 2024, 134 (8) e179560 | https://doi.org/10.1172/JCI179560
VHL governs m6A modification and PIK3R3 mRNA stability in clear cell renal cell carcinomas
Hyemin Lee,1 Li Zhuang,1 and Boyi Gan1,2
1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
2The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, Texas, USA.
Address correspondence to: Boyi Gan
Abstract
N6-Methyladenosine (m6A), a prevalent posttranscriptional modification, plays an important role in cancer progression. Clear cell renal cell carcinoma (ccRCC) is chiefly associated with the loss of the von Hippel-Lindau (VHL) gene, encoding a component of the E3 ubiquitin ligase complex. In this issue of the JCI, Zhang and colleagues unveiled a function of VHL beyond its canonical role as an E3 ubiquitin ligase in regulating hypoxia-inducible factors (HIFs). It also governed m6A modification by orchestrating the assembly of m6A writer proteins METTL3 and METTL14, thereby stabilizing PIK3R3 mRNA. Mechanistically, PIK3R3 contributed to p85 ubiquitination, which restrained PI3K/AKT signaling and consequently impeded ccRCC growth in cell and mouse models. This discovery provides potential treatment targets in VHL-deficient ccRCCs.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-18)
- 국외 연구진
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