SynthesisThe Journal of pathology2012
Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target.
Synthesis in The Journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 66 papers, 2 of them syntheses that pooled it.
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
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis.BioMed research international · 2015Pooled it
- Steroid receptor coactivator-3 regulates glucose metabolism in bladder cancer cells through coactivation of hypoxia inducible factor 1α.The Journal of biological chemistry · 2014Trial
- SLC16A3 links tumor metabolism to therapeutic opportunities in hepatocellular carcinoma.Translational cancer research · 2026Review
- Redox Homeostasis, Metabolic Pathways and Plasticity in Uveal Melanoma Compared to Other Cancers.Cancers · 2026Review
- Comprehensive pan-cancer analysis identified SLC16A3 as a potential prognostic and diagnostic biomarker.Cancer cell international · 2025Article
- Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.Oncogene · 2025Article
- Metabolic alterations in hereditary and sporadic renal cell carcinoma.Nature reviews. Nephrology · 2024Review
- Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription.Clinical and translational medicine · 2024Review
- Construction of a prediction model for prognosis of bladder cancer based on the expression of ion channel-related genes.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Paralog-dependent isogenic cell assay cascade generates highly selective SLC16A3 inhibitors.Cell chemical biology · 2023Article
- Biological Biomarkers of Response and Resistance to Immune Checkpoint Inhibitors in Renal Cell Carcinoma.Cancers · 2023Review
- Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022Review
- A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population.Nature communications · 2022Article
- Article
- HyperpolarizedCancers · 2022Article
- The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma.Frontiers in pharmacology · 2022Article
- Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma.International journal of biological sciences · 2022Article
- Article
- Metabolic imaging with hyperpolarizedCancer · 2021Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrigendum.2015
Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of kidney cancer. Here, we integrated an unbiased genome-wide RNA interference screen for ccRCC survival regulators with an analysis of recurrently overexpressed genes in ccRCC to identify new therapeutic targets in this disease. One of the most potent survival regulators, the monocarboxylate transporter MCT4 (SLC16A3), impaired ccRCC viability in all eight ccRCC lines tested and was the seventh most overexpressed gene in a meta-analysis of five ccRCC expression datasets. MCT4 silencing impaired secretion of lactate generated through glycolysis and induced cell cycle arrest and apoptosis. Silencing MCT4 resulted in intracellular acidosis, and reduction in intracellular ATP production together with partial reversion of the Warburg effect in ccRCC cell lines. Intra-tumoural heterogeneity in the intensity of MCT4 protein expression was observed in primary ccRCCs. MCT4 protein expression analysis based on the highest intensity of expression in primary ccRCCs was associated with poorer relapse-free survival, whereas modal intensity correlated with Fuhrman nuclear grade. Consistent with the potential selection of subclones enriched for MCT4 expression during disease progression, MCT4 expression was greater at sites of metastatic disease. These data suggest that MCT4 may serve as a novel metabolic target to reverse the Warburg effect and limit disease progression in ccRCC.
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.