ArticleThe Journal of clinical investigation2024
Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 13 citations in OpenAlex.
- Article
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Beyond mBiomedicines · 2026Review
- Recent advances in etiology and treatment of von Hippel-Lindau Disease (VHLD).Cancer metastasis reviews · 2026Review
- Epitranscriptomic silencing of the ZC3H13/mJournal of experimental & clinical cancer research : CR · 2026Article
- Epitranscriptomics in kidney disease: insights and therapeutic potential.Kidney research and clinical practice · 2026Article
- Bidirectional regulation of the ubiquitin-RNA modification axis in cancer.Frontiers in oncology · 2026Review
- The dual regulatory role of METTL14-mediated mFrontiers in oncology · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- The Central Role of m6A as Epigenetic Regulator in Metabolic Disorders of Therapeutic Potential and Clinical Implications.Molecular neurobiology · 2025Review
- Deciphering the interplay between SETD2 mediated H3K36me3 and RNA N6-methyladenosine in clear cell renal cell carcinoma (ccRCC).Epigenetics · 2025Article
- Hypoxia-mediated regulation of mRNA metabolism: from transcription to stability.Cell communication and signaling : CCS · 2025Review
- FTO Promotes Hepatocellular Carcinoma Progression by Mediating m6A Modification of BUB1 and Targeting TGF-βR1 to Activate the TGF-β Signaling Pathway.Journal of clinical and translational hepatology · 2025Article
- The Hippo pathway effector YAP inhibits NF-κB signaling and ccRCC growth by opposing ZHX2.The Journal of biological chemistry · 2025Article
- Roles of E3 ubiquitin ligases and deubiquitinating enzymes in renal cell carcinoma.Frontiers in oncology · 2025Review
- Article
- METTL Family in Healthy and Disease.Molecular biomedicine · 2024Review
- VHL governs m6A modification and PIK3R3 mRNA stability in clear cell renal cell carcinomas.The Journal of clinical investigation · 2024Article
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20 authors at 6 institutions in 1 country.
Funding
Abstract
N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.