ArticleCell death & disease2021
VHL regulates the sensitivity of clear cell renal cell carcinoma to SIRT4-mediated metabolic stress via HIF-1α/HO-1 pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 38 citations in OpenAlex.
- A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.Renal failure · 2026Review
- Renal cell carcinoma: molecular understanding and therapeutic development.Cell death and differentiation · 2026Review
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- Natural Products in Clear Cell Renal Cell Carcinoma: Rewiring the VHL-HIF Axis, Metabolic Plasticity, and Tumor-Immune Interactions.International journal of molecular sciences · 2026Review
- Article
- Mechanistic Research on the Crosstalk Between Macrophage Polarization and Energy Metabolic Reprogramming in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- The P2Y13 receptor-mediated microglial morphological transformation through the p38MAPK signaling pathway contributes to central sensitization in a murine model of chronic migraine.The journal of headache and pain · 2025Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- SIRT4 Protects Müller Glial Cells Against Apoptosis by Mediating Mitochondrial Dynamics and Oxidative Stress.Molecular neurobiology · 2025Article
- Identifying potential risk genes for clear cell renal cell carcinoma with deep reinforcement learning.Nature communications · 2025Article
- Identification of the LCOR-PLCL1 pathway that restrains lipid accumulation and tumor progression in clear cell renal cell carcinoma.International journal of biological sciences · 2025Article
- Sirtuin insights: bridging the gap between cellular processes and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- The role of Klotho and sirtuins in sleep-related cardiovascular diseases: a review study.npj aging · 2024Review
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
- Targeting Mitochondrial Sirtuins in Age-Related Neurodegenerative Diseases and Fibrosis.Aging and disease · 2023Review
- The SIRT7-mediated deacetylation of CHD1L amplifies HIF-2α-dependent signal that drives renal cell carcinoma progression and sunitinib resistance.Cell & bioscience · 2023Article
- Advances of SIRT4 in cancer metabolism and therapy.Pediatric discovery · 2023Review
- PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis.International journal of molecular sciences · 2023Review
- The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Clear cell renal cell carcinomas (ccRCC) reprogram carbon metabolism responses to hypoxia, thereby promoting utilization of glutamine. Recently, sirtuin 4 (SIRT4), a novel molecular has turned out to be related to alternating glutamine metabolism and modulating the tumor microenvironment. However, the role of SIRT4 in ccRCC remains poorly understood. Here, we illustrated that the expression of SIRT4 is markedly reduced in cancerous tissues, and closely associated with malignancy stage, grade, and prognosis. In ccRCC cells, SIRT4 exerted its proapoptotic activity through enhancing intracellular reactive oxygen species (ROS). Heme oxygenase-1 (HO-1) is part of an endogenous defense system against oxidative stress. Nevertheless, overexpression of SIRT4 hindered the upregulation of HO-1 in von Hippel-Lindau (VHL)-proficient cells and repressed its expression in VHL-deficient cells. This discrepancy indicated that competent VHL withstands the inhibitory role of SIRT4 on HIF-1α/HO-1. Functionally, overexpression of HO-1 counteracted the promotional effects of SIRT4 on ROS accumulation and apoptosis. Mechanistically, SIRT4 modulates ROS and HO-1 expression via accommodating p38-MAPK phosphorylation. By contrast, downregulation of p38-MAPK by SB203580 decreased intracellular ROS level and enhanced the expression of HO-1. Collectively, this work revealed a potential role for SIRT4 in the stimulation of ROS and the modulation of apoptosis. SIRT4/HO-1 may act as a potential therapeutic target, especially in VHL-deficient ccRCCs.
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.