ArticleJournal of translational medicine2019
PYCR1 interference inhibits cell growth and survival via c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathway in hepatocellular cancer.
Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- Study on the effects and mechanisms of M2 macrophages on PYCR1-promoted biological behavior of hepatocellular carcinoma cells.Scientific reports · 2026Article
- PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism.Molecular oncology · 2026Article
- The key enzyme PYCR1 in proline metabolism: a dual driver of cancer progression and fibrotic remodeling.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Screening a knowledge-based library of low molecular weight compounds against the proline biosynthetic enzyme 1-pyrroline-5-carboxylate 1 (PYCR1).Protein science : a publication of the Protein Society · 2024Article
- Comprehensive proteogenomic characterization of rare kidney tumors.Cell reports. Medicine · 2024Article
- Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions.MedComm · 2024Review
- Novel Fragment Inhibitors of PYCR1 from Docking-Guided X-ray Crystallography.Journal of chemical information and modeling · 2024Article
- LINC01123 acts as an oncogenic driver in lung adenocarcinoma by regulating the miR-4766-5p/PYCR1 axis.Histology and histopathology · 2023Article
- Integrated analysis of the roles of oxidative stress related genes and prognostic value in clear cell renal cell carcinoma.Journal of cancer research and clinical oncology · 2023Article
- IGF1R-phosphorylated PYCR1 facilitates ELK4 transcriptional activity and sustains tumor growth under hypoxia.Nature communications · 2023Article
- Associations between prenatal organophosphate pesticide exposure and placental gene networks.Environmental research · 2023Article
- Targeting PYCR2 inhibits intraperitoneal metastatic tumors of mouse colorectal cancer in a proline-independent approach.Cancer science · 2023Article
- Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?Frontiers in oncology · 2023Review
- Low-dose radiation exaggerates HFD-induced metabolic dysfunction by gut microbiota through PA-PYCR1 axis.Communications biology · 2022Article
- Review
- Shikonin induces apoptosis and autophagy via downregulation of pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cells.Bioengineered · 2022Article
- Pyrroline-5-Carboxylate Reductase 1: a novel target for sensitizing multiple myeloma cells to bortezomib by inhibition of PRAS40-mediated protein synthesis.Journal of experimental & clinical cancer research : CR · 2022Article
- Survival and clinicopathological significance of PYCR1 expression in cancer: A meta-analysis.Frontiers in oncology · 2022Article
- PYCR1: A Potential Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.Journal of Cancer · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver cancer is the second leading causes of cancer-related death globally. Pyrroline-5-carboxylate reductase 1 (PYCR1) plays a critical role in metabolic profiles of tumors. Therefore, it is necessary to explore the mechanisms of PYCR1 on cell growth and survival in hepatocellular carcinoma (HCC).
methodsProtein and mRNA expression levels of PYCR1 in 140 pairs of tumor and adjacent normal liver tissues of HCC patients were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Expressions of PYCR1 were inhibited in BEL-7404 cells and SMMC-7721 cells using gene interference technology. The cell proliferation was detected by Celigo and MTT assay. The colony formation assay was also performed. The cell apoptosis was measured by flow cytometric assay. The effect of PYCR1 interference on tumor growth was observed by xenograft nude mice assay in vivo. The downstream pathway of PYCR1 interference was searched by microarray and bioinformatics analysis, and validated by qRT-PCR and western blot.
resultsPYCR1 levels were significantly up-regulated in HCC tumor tissues than adjacent normal liver tissues in both protein and mRNA levels (P < 0.01). In vitro, the cell proliferation was significantly slower in shPYCR1 group than shCtrl group in BEL-7404 and SMMC-7721 cells (P < 0.001). The colony number was significantly smaller after PYCR1 interference (P < 0.01). The percentage of apoptosis cells significantly increased in shPYCR1 group (P < 0.01). In vivo, PYCR1 interference could obviously suppress tumor growth in xenograft nude mice. The volume and weight of tumors were significantly smaller via PYCR1 interference. The c-Jun N-terminal kinase (JNK) signaling pathway significantly altered, and insulin receptor substrate 1 (IRS1) were significantly down-regulated by PYCR1 interference in both mRNA and protein levels (P < 0.001).
conclusionPYCR1 interference could inhibit cell proliferation and promote cell apoptosis in HCC through regluting JNK/IRS1 pathway. Our study will provide a drug target for HCC therapy and a potential biomarker for its diagnosis or prognosis.
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