ArticleJournal of translational medicine2024
PTBP1 crotonylation promotes colorectal cancer progression through alternative splicing-mediated upregulation of the PKM2 gene.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- RBMX promotes colorectal liver metastasis by stabilizing MTHFD2 mRNA to regulate redox homeostasis.Cellular and molecular life sciences : CMLS · 2026Article
- Multivariable genome-wide analysis elucidates the shared genetic architecture, immunosenescence features, and gut-origin therapeutic targets of ulcerative colitis-associated multisystem inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- hnRNPA1-SF3B3 interaction drives radioresistance in oral squamous cell carcinoma by modulating MARF1 alternative splicing isoforms.Journal of experimental & clinical cancer research : CR · 2026Article
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- Harnessing Ribonucleoprotein Granule Biology for Cancer Therapy: The Central Role of Protein Modifications.Research (Washington, D.C.) · 2026Review
- A putative prognostic model for lung adenocarcinoma based on crotonylation-related genes by bioinformatics and experimental verification.Frontiers in cell and developmental biology · 2026Article
- Blocking Lysine Crotonylation and Aerobic Glycolysis as Targeting Strategy Against mpox Virus Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypoxic Reprogramming of ACOX1-Driven HSP90AB1 Crotonylation Stabilizes Thioredoxin to Orchestrate Redox Homeostasis in Oral Squamous Cell Carcinoma.Research (Washington, D.C.) · 2026Article
- Protein crotonylation in cancer: mechanisms, functions, and therapeutic potential.Cell biology and toxicology · 2025Review
- APDCA: An accurate and effective method for predicting associations between RBPs and AS-events during epithelial-mesenchymal transition.PLoS computational biology · 2025Article
- Glucose Metabolic Reprogramming in Colorectal Cancer: From Mechanisms to Targeted Therapy Approaches.Cancer medicine · 2025Review
- Exploring the Link Between Noncoding RNAs and Glycolysis in Colorectal Cancer.Journal of cellular and molecular medicine · 2025Review
- Targeting Glycolysis for Treatment of Breast Cancer Resistance: Current Progress and Future Prospects.International journal of biological sciences · 2025Review
- Alternative splicing factor RAB3IP as a novel risk signature to predict the prognosis of colorectal cancer.Journal of Cancer · 2025Article
- Fungi-Kcr: a language model for predicting lysine crotonylation in pathogenic fungal proteins.Frontiers in cellular and infection microbiology · 2025Article
- PKM2-driven metabolic reprogramming in digestive system tumors: mechanisms, therapeutic advances, and clinical challenges.Frontiers in immunology · 2025Review
- Splicing factor PTBP1 promotes hepatocarcinogenesis via oncogenic splice-switching of MAPT.Oncology research · 2025Article
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13 authors.
Funding
Abstract
backgroundAerobic glycolysis is a tumor cell phenotype and a hallmark in cancer research. The alternative splicing of the pyruvate kinase M (PKM) gene regulates the expressions of PKM1/2 isoforms and the aerobic glycolysis of tumors. Polypyrimidine tract binding protein (PTBP1) is critical in this process; however, its impact and underlying mechanisms in colorectal cancer (CRC) remain unclear. This study aimed to investigate the role of PTBP1 crotonylation in CRC progression.
methodsThe crotonylation levels of PTBP1 in human CRC tissues and cell lines were analyzed using crotonylation proteomics and immunoprecipitation. The main crotonylation sites were identified by immunoprecipitation and immunofluorescent staining. The glycolytic capacities of CRC cells were evaluated by measuring the glucose uptake, lactate production, extracellular acidification rate, and glycolytic proton efflux rate. The role and mechanism of PTBP1 crotonylation in PKM alternative splicing were determined by Western blot, quantitative real-time PCR (RT-qPCR), RNA immunoprecipitation, and immunoprecipitation. The effects of PTBP1 crotonylation on the behaviors of CRC cells and CRC progression were assessed using CCK-8, colony formation, cell invasion, wound healing assays, xenograft model construction, and immunohistochemistry.
resultsThe crotonylation level of PTBP1 was elevated in human CRC tissues compared to peritumor tissues. In CRC tissues and cells, PTBP1 was mainly crotonylated at K266 (PTBP1 K266-Cr), and lysine acetyltransferase 2B (KAT2B) acted as the crotonyltranferase. PTBP1 K266-Cr promoted glycolysis and lactic acid production, increasing the PKM2/PKM1 ratio in CRC tissues and cells. Mechanistically, PTBP1 K266-Cr enhanced the interaction of PTBP1 with heterogeneous nuclear ribonucleoprotein A1 and A2 (hnRNPA1/2), thus affecting the PKM alternative splicing. PTBP1 K266-Cr facilitated CRC cell proliferation, migration, and metastasis in vitro and in vivo. Pathologically, a high level of PTBP1 K266-Cr was associated with poor prognosis in CRC patients.
conclusionsCrotonylation of PTBP1 coordinates tumor cell glycolysis and promotes CRC progression by regulating PKM alternative splicing and increasing PKM2 expression.
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