ArticleMolecular biology of the cell2014
Alternative splicing of human NT5E in cirrhosis and hepatocellular carcinoma produces a negative regulator of ecto-5'-nucleotidase (CD73).
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Article
- Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Article
- Third-Generation CD73 Inhibitors Based on a 4,6-Disubstituted-2-Thiopyridine Scaffold.ChemMedChem · 2025Article
- Influence of CCancers · 2023Article
- The Clinical Significance of CD73 in Cancer.International journal of molecular sciences · 2023Review
- Circulating Ectonucleotidases Signal Impaired Myocardial Perfusion at Rest and Stress.Journal of the American Heart Association · 2023Article
- CD73, a Promising Therapeutic Target of Diclofenac, Promotes Metastasis of Pancreatic Cancer through a Nucleotidase Independent Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma.Frontiers in pharmacology · 2023Article
- Novel microRNAs modulating ecto-5'-nucleotidase expression.Frontiers in immunology · 2023Article
- CD73, a significant protein in liver diseases.Frontiers in medicine · 2023Review
- Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer.Frontiers in immunology · 2023Review
- Article
- RNA splicing: a dual-edged sword for hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2022Review
- An Alternatively Spliced Variant of METTL3 Mediates Tumor Suppression in Hepatocellular Carcinoma.Genes · 2022Article
- Screening of Prognostic Markers for Hepatocellular Carcinoma Patients Based on Multichip Combined Analysis.Computational and mathematical methods in medicine · 2022Article
- Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients.EBioMedicine · 2021Article
- The elegant complexity of mammalian ecto-5'-nucleotidase (CD73).Trends in cell biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ecto-5'-nucleotidase (CD73), encoded by NT5E, is the major enzymatic source of extracellular adenosine. CD73 controls numerous pathophysiological responses and is a potential disease target, but its regulation is poorly understood. We examined NT5E regulation by alternative splicing. Genomic database analysis of human transcripts led us to identify NT5E-2, a novel splice variant that was expressed at low abundance in normal human tissues but was significantly up-regulated in cirrhosis and hepatocellular carcinoma (HCC). NT5E-2 encodes a shorter CD73 isoform we named CD73S. The presence of CD73S protein, which lacks 50 amino acids, was detected in HCC using an isoform-specific antibody. A noncanonical mouse mRNA, similar to human CD73S, was observed, but the corresponding protein was undetectable. The two human isoforms exhibited functional differences, such that ectopic expression of canonical CD73 (CD73L) in human HepG2 cells was associated with decreased expression of the proliferation marker Ki67, whereas CD73S expression did not have an effect on Ki67 expression. CD73S was glycosylated, catalytically inactive, unable to dimerize, and complexed intracellularly with the endoplasmic reticulum chaperone calnexin. Furthermore, CD73S complexed with CD73L and promoted proteasome-dependent CD73L degradation. The findings reveal species-specific CD73 regulation, with potential significance to cancer, fibrosis, and other diseases characterized by changes in CD73 expression and function.
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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.