Citations to this article
Citation Information: J Clin Invest. 2024;134(8):e179560. https://doi.org/10.1172/JCI179560.
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.
Authors
Hyemin Lee, Li Zhuang, Boyi Gan
Citations to this article (3)
| Title and authors | Publication | Year |
|---|---|---|
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N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway
An TY, Hu QM, Ni P, Hua YQ, Wang D, Duan GC, Chen SY, Jia B |
World journal of gastrointestinal oncology | 2024 |
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METTL Family in Healthy and Disease.
He J, Hao F, Song S, Zhang J, Zhou H, Zhang J, Li Y |
Molecular biomedicine | 2024 |
|
Critical role of non-coding RNA-mediated ferroptosis in urologic malignancies
Li W, Zheng L, Luo P, Chen T, Zou J, Chen Q, Cheng L, Gan L, Zhang F, Qian B |
Frontiers in Immunology | 2024 |
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