ArticleCancer communications (London, England)2021
The role of the HIF-1α/ALYREF/PKM2 axis in glycolysis and tumorigenesis of bladder cancer.
Article in Cancer communications (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers, 2 of them syntheses that pooled it.
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Who cites it
213 citing papers in PubMed, 2 syntheses or guidelines pooled it, 303 citations in OpenAlex.
- Role of m5C methylation in digestive system tumors (Review).Molecular medicine reports · 2025Pooled it
- Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets.Genes, chromosomes & cancer · 2024Pooled it
- The MYBL2-GTSE1 axis promotes laryngeal squamous cell carcinoma progression by regulating PI3K/AKT-dependent glycolytic reprogramming.Cancer biology & therapy · 2026Article
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Article
- Artemisinin inhibits colorectal cancer progression via the FAM83A-AS1/HIF-1α axis.Journal of gastrointestinal oncology · 2026Article
- Mechanistic Study of m5C Modification in Stem Cell Differentiation and Disease Regulation.Stem cell reviews and reports · 2026Review
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
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- RNA modifications in cancer: regulators of tumor evolution and therapeutic response.Molecular cancer · 2026Review
- PRRC2A-mediated mCell death & disease · 2026Article
- Role of RNA 5‑methylcytosine modification in cancer: Insights from coding and non‑coding RNAs (Review).Molecular medicine reports · 2026Review
- Identification of alpha1-oleate as a potent regulator of adipokine-dependent metabolism, in bladder cancer tissue.Cancer & metabolism · 2026Article
- Metabolic Perspective on Atherosclerosis: Macrophage Reprogramming and Novel Therapeutic Targets.Journal of the American Heart Association · 2026Review
- Targeting HIF-1α promotes ferroptosis and boosts antitumor immunity in MSS colorectal cancer.Redox biology · 2026Article
- Downregulated m⁵C regulator NSUN6 enhances proliferation, migration and affects immune regulation in ovarian cancer.Scientific reports · 2026Article
- H3K18 lactylation promotes glycolysis in bladder cancer via inhibiting GNG7 through regulating PI3K-AKT signaling pathway.World journal of surgical oncology · 2026Article
- Epitranscriptomic control of cancer: the emerging roles of m⁵C and ac⁴C RNA modifications.Cell death discovery · 2026Review
- NSUN2/ALYREF-mediated RNA m5c modification promotes anoikis resistance of prostate cancer through activating autophagy.Oncogene · 2026Article
- The RNA methylation modification as an immunometabolic regulatory hub in pancreatic cancer: from mechanistic insights to clinical translation perspectives.Molecular cancer · 2026Review
153 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs a rate-limiting enzyme of glycolysis, pyruvate kinase muscle isozyme M2 (PKM2) participates in tumor metabolism and growth. The regulatory network of PKM2 in cancer is complex and has not been fully studied in bladder cancer. The 5-methylcytidine (m5C) modification in PKM2 mRNA might participate in the pathogenesis of bladder cancer and need to be further clarified. This study aimed to investigate the biological function and regulatory mechanism of PKM2 in bladder cancer.
methodsThe expression of PKM2 and Aly/REF export factor (ALYREF) was measured by Western blotting, qRT-PCR, and immunohistochemistry. The bioprocesses of bladder cancer cells were demonstrated by a series of experiments in vitro and in vivo. RNA immunoprecipitation, RNA-sequencing, and dual-luciferase reporter assays were conducted to explore the potential regulatory mechanisms of PKM2 in bladder cancer.
resultsIn bladder cancer, we first demonstrated that ALYREF stabilized PKM2 mRNA and bound to its m5C sites in 3'-untranslated regions. Overexpression of ALYREF promoted bladder cancer cell proliferation by PKM2-mediated glycolysis. Furthermore, high expression of PKM2 and ALYREF predicted poor survival in bladder cancer patients. Finally, we found that hypoxia-inducible factor-1alpha (HIF-1α) indirectly up-regulated the expression of PKM2 by activating ALYREF in addition to activating its transcription directly.
conclusionsThe m5C modification in PKM2 mRNA in the HIF-1α/ALYREF/PKM2 axis may promote the glucose metabolism of bladder cancer, providing a new promising therapeutic target for bladder cancer.
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