ArticleClinical and translational medicine2024
PYCR1 promotes liver cancer cell growth and metastasis by regulating IRS1 expression through lactylation modification.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Integrating virtual screening and molecular dynamics simulations to identify emodin as a PYCR1 inhibitor modulating docetaxel sensitivity in prostate cancer.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- XPA lactylation is required for UV-induced DNA damage repair.Nucleic acids research · 2026Article
- H3K18 Lactylation Promotes Cell Proliferation in T-Cell Acute Lymphoblastic Leukemia.Journal of cellular biochemistry · 2026Article
- Pyrroline-5-carboxylate reductase 1 interacts with Nudix hydrolase 5 to drive bladder cancer malignant progression via activation of the APOE/JAK2/STAT3 signalling axis.Clinical and translational medicine · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- PYCR1 modulates ferroptosis and malignant phenotypes of clear cell renal cell carcinoma through proline biosynthesis.Molecular biology reports · 2026Article
- PYCR1 promotes glutamine metabolism and the progression of lung adenocarcinoma by regulating the expression of OPLAH.Clinical and experimental medicine · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- Serendipitous discovery of an allosteric inhibitor binding groove in the proline biosynthetic enzyme pyrroline-5-carboxylate reductase 1.The Biochemical journal · 2026Article
- SATB2 Mediates H3K9 Delactylation by Recruiting HDAC3 to Repress LCN2 and Inhibit Lung Tumor Growth and Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-omics analyses related to mitochondria and ageing in triple-negative breast cancer implicate PYCR1 potentiates tumor progression.Cancer cell international · 2026Article
- [Research Progress on the Role and Mechanisms of PYCR1 in Tumorigenesis and Progression].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Protein lactylation in metabolic dysfunction-associated steatotic liver disease: a mechanistic review.Diabetology & metabolic syndrome · 2026Review
- Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance.Gastroenterology report · 2026Review
- lncRNA NEAT1 promotes the proliferation of hemangioma cells by transcriptionally activating β‑catenin via enhancing H3K18 lactylation.Molecular medicine reports · 2026Article
- [ERI3 expression is elevated in hepatocellular carcinoma and correlates with poor patient prognosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Integrated multi-omics analysis of metabolomics and proteomics uncovers dysregulated amino acid metabolism in HCC metastasis.Frontiers in immunology · 2026Article
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
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17 authors.
Funding
Abstract
backgroundLiver cancer (LC) is among the deadliest cancers worldwide, with existing treatments showing limited efficacy. This study aimed to elucidate the role and underlying mechanisms of pyrroline-5-carboxylate reductase 1 (PYCR1) as a potential therapeutic target in LC.
methodsImmunohistochemistry and Western blot were used to analyse the expression of PYCR1 in LC cells and tissues. EdU assays, colony-forming assays, scratch wound healing assays, Transwell assays, nude mouse xenograft models and nude mouse lung metastasis models were used to detect the growth and metastasis abilities of LC cells. Transcriptome sequencing was used to search for downstream target genes regulated by PYCR1, and metabolomics was used to identify the downstream metabolites regulated by PYCR1. ChIP assays were used to analyse the enrichment of H3K18 lactylation in the IRS1 promoter region.
resultsWe found that the expression of PYCR1 was significantly increased in HCC and that this high expression was associated with poor prognosis in HCC patients. Knockout or inhibition of PYCR1 inhibited HCC cell proliferation, migration and invasion both in vivo and in vitro. In addition, we revealed that knocking out or inhibiting PYCR1 could inhibit glycolysis in HCC cells and reduce H3K18 lactylation of the IRS1 histone, thereby inhibiting IRS1 expression.
conclusionsOur findings identify PYCR1 as a pivotal regulator of LC progression that influences tumour cell metabolism and gene expression. By demonstrating the potential of targeting PYCR1 to inhibit LC cell proliferation and metastasis, this study identified PYCR1 as a promising therapeutic target for LC. HIGHLIGHTS: Pyrroline-5-carboxylate reductase 1 (PYCR1) promotes the proliferation and metastasis of liver cancer (LC) cells. The expression of PYCR1 in LC is regulated by DNA methylation. Knocking down or inhibiting PYCR1 inhibits glycolysis as well as the PI3K/AKT/mTOR and MAPK/ERK pathways in LC cells. PYCR1 regulates the transcriptional activity of IRS1 by affecting H3K18 lactylation in its promoter region.
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