ArticleCell & bioscience2024
SIRT6 deficiency impairs the deacetylation and ubiquitination of UHRF1 to strengthen glycolysis and lactate secretion in bladder cancer.
Article in Cell & bioscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed.
- Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic networks to breast cancer survival.GeroScience · 2026Article
- UHRF1 as an epigenetic therapeutic target in Cancer.Molecular biology reports · 2026Review
- Aerobic glycolysis in bladder cancer: research advances and targeted therapy potential.Frontiers in oncology · 2026Review
- Apigenin Suppresses Bladder Cancer via the SIRT6-NCOA2-PPARα Axis.International journal of biological sciences · 2026Article
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- Myc-associated zinc finger protein drives colorectal cancer metastasis through activating ubiquitin like with ring finger protein one.World journal of gastrointestinal oncology · 2025Article
- UHRF1 and NF-κB signaling in prostate cancer progression insights from bioinformatics and experimental validation.BMC cancer · 2025Article
- Sirtuins and tumor immunity: mechanistic insights, immunotherapy prospects, and therapeutic horizons.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
backgroundAberrant interplay between epigenetic reprogramming and metabolic rewiring events contributes to bladder cancer progression and metastasis. How the deacetylase Sirtuin-6 (SIRT6) regulates glycolysis and lactate secretion in bladder cancer remains poorly defined. We thus aimed to study the biological functions of SIRT6 in bladder cancer.
methodsBioinformatic analysis was used to study the prognostic significance of SIRT6/UHRF1 in BLCA. Both in vitro and in vivo assays were used to determine the roles of SIRT6/UHRF1 in BLCA. Deacetylation and ubiquitin assays were performed to uncover the regulations of SIRT6-UHRF1. Measurement of extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) was used to assess glycolytic abilities.
resultsHere, we show that protein deacetylase SIRT6 was down-regulated in BLCA, and predicts poor overall survival. SIRT6 deficiency notably enhances BLCA cell proliferation, self-renewal, and migration capacities in vitro and in vivo. Mechanistically, SIRT6 interacts with, deacetylates, and promotes UHRF1 degradation mediated by β-TrCP1. Thus, SIRT6 deficiency leads to stabilized UHRF1 and depends on UHRF1 to accelerate BLCA malignant progression. Furthermore, UHRF1 significantly increased aerobic glycolysis via activating MCT4/HK2 expressions. Down-regulated SIRT6 thus depended on UHRF1 to promote glycolysis and lactate secretion in BLCA. Targeting UHRF1 or MCT4 notably impaired the extracellular lactate accumulations in BLCA. Significantly, a specific small-molecule inhibitor (NSC232003) targeting UHRF1 substantially inhibited SIRT6-deficient BLCA progression.
conclusionTogether, our study uncovered an epigenetic mechanism of the SIRT6/UHRF1 axis in driving BLCA glycolysis and lactate secretion, creating a novel vulnerability for BLCA treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.