ArticleClinical and translational medicine2021
NNT-induced tumor cell "slimming" reverses the pro-carcinogenesis effect of HIF2a in tumors.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Thyroid Hormone Receptor β1 and PGC1α Coordinately Regulate OPA1/MFN2-Mediated Mitochondrial Fusion and UCP1-Mediated Lipid Browning in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Combination of Pterocarpus marsupium Bark Extract, Pinus strobus Bark Extract, and Ascorbyl Tetraisopalmitate Inhibits Melanogenesis via Nicotinamide Nucleotide Transhydrogenase Activation.Journal of cosmetic dermatology · 2025Article
- NCOA7 inhibits renal cancer progression by inducing autophagy and lipid metabolism through V-ATPase interaction.Cell death discovery · 2025Article
- PUMA reduces FASN ubiquitination to promote lipid accumulation and tumor progression in human clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
- A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway.Molecular cancer · 2024Article
- HIF2α Promotes Cancer Metastasis through TCF7L2-Dependent Fatty Acid Synthesis in ccRCC.Research (Washington, D.C.) · 2024Article
- Downregulation of RNA binding protein 47 predicts low survival in patients and promotes the development of renal cell malignancies through RNA stability modification.Molecular biomedicine · 2023Article
- N6-methyladenosine-modified DBT alleviates lipid accumulation and inhibits tumor progression in clear cell renal cell carcinoma through the ANXA2/YAP axis-regulated Hippo pathway.Cancer communications (London, England) · 2023Article
- High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma.Pharmacogenomics and personalized medicine · 2023Article
- Treatment strategies for clear cell renal cell carcinoma: Past, present and future.Frontiers in oncology · 2023Review
- KDELR2-KIF20A axis facilitates bladder cancer growth and metastasis by enhancing Golgi-mediated secretion.Biological procedures online · 2022Article
- Potential biomarkers and targets of mitochondrial dynamics.Clinical and translational medicine · 2021Review
- Biomarker Screening and Prognostic Significance Analysis for Renal Cell Carcinoma.International journal of general medicine · 2021Article
- NNT-induced tumor cell "slimming" reverses the pro-carcinogenesis effect of HIF2a in tumors.Clinical and translational medicine · 2021Article
- Analysis of Peroxisomal ABCD3 Transporter as a Prognostic Factor in Clear Cell Renal Cell Carcinoma.Cancer genomics & proteomicsArticle
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHIF2a and lipid accumulation play key roles in the progression of clear cell renal cell carcinoma (ccRCC). Tumor cell "slimming" is a new concept in which tumor cells with abnormal lipids efficiently consume lipids to inhibit tumor progression without producing additional ATP. However, their respective regulatory mechanisms are still unclear. The purpose of this study is uncovering the links between these three key elements of ccRCC to elucidate new mechanisms of ccRCC metabolic abnormalities and providing a basis for new drug development for ccRCC.
methodsBioinformatics screening and analyses were performed in ccRCC according to TCGA-KIRC database. qRT-PCR, luciferase reporter assay, western blot, chromatin immunoprecipitation (ChIP) assays, and other biological methods were used to explore and verify related pathways. Various cell line models and animal models were used to perform related functional experiments.
resultsScreening based on sequencing data after HIF2a knockdown and three independent mitochondrial metabolism-related gene sets showed that nicotinamide nucleotide transhydrogenase (NNT) was a mediator between HIF2a and tumor cells "slimming." Further research showed that NNT had significant prognostic predictive value and was downregulated in ccRCC. It is regulated by HIF2a and can significantly activate lipid browning-mediated tumor cell "slimming." Mechanistic investigations indicated that HIF2a enhanced the expression of miR-455-5p via binding to HIF2a-related response elements in the miR-455-5p promoter, which suppresses NNT expression by binding to its 3' untranslated region.
conclusionsOur study revealed a novel mechanism by which HIF2a decreased NNT level through a microRNA that suppressed tumor cell "slimming," resulting in the progression of ccRCC. This mechanism provides a fresh perspective of lipid accumulation in ccRCC and may help target novel strategies for the treatment of tumors with abnormal lipid metabolism.
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