دورية أكاديمية

Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer

التفاصيل البيبلوغرافية
العنوان: Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer
المؤلفون: Di Matteo, A, Belloni, E, Pradella, D, Chiaravalli, AM, Pini, GM, Bugatti, M, Alfieri, R, Barzan, C, Franganillo Tena, E, Bione, S, Terenzani, E, Sessa, F, Wyatt, CDR, Vermi, W, Ghigna, C
المصدر: International Journal of Molecular Sciences , 24 (9) , Article 8102. (2023)
سنة النشر: 2023
المجموعة: University College London: UCL Discovery
مصطلحات موضوعية: RNA binding proteins, alternative splicing, angiogenesis, cancer biomarkers, gastric cancer, tumor vasculature, Up-Regulation, Endothelial Cells, Stomach Neoplasms, Neovascularization, Pathologic, Humans, Male, Female, Adult, Middle Aged, Aged, 80 and over, Biomarkers, Prognosis, Cells, Cultured, Animals, Mice
الوصف: Angiogenesis is crucial for cancer progression. While several anti-angiogenic drugs are in use for cancer treatment, their clinical benefits are unsatisfactory. Thus, a deeper understanding of the mechanisms sustaining cancer vessel growth is fundamental to identify novel biomarkers and therapeutic targets. Alternative splicing (AS) is an essential modifier of human proteome diversity. Nevertheless, AS contribution to tumor vasculature development is poorly known. The Neuro-Oncological Ventral Antigen 2 (NOVA2) is a critical AS regulator of angiogenesis and vascular development. NOVA2 is upregulated in tumor endothelial cells (ECs) of different cancers, thus representing a potential driver of tumor blood vessel aberrancies. Here, we identified novel AS transcripts generated upon NOVA2 upregulation in ECs, suggesting a pervasive role of NOVA2 in vascular biology. In addition, we report that NOVA2 is also upregulated in ECs of gastric cancer (GC), and its expression correlates with poor overall survival of GC patients. Finally, we found that the AS of the Rap Guanine Nucleotide Exchange Factor 6 (RapGEF6), a newly identified NOVA2 target, is altered in GC patients and associated with NOVA2 expression, tumor angiogenesis, and poor patient outcome. Our findings provide a better understanding of GC biology and suggest that AS might be exploited to identify novel biomarkers and therapeutics for anti-angiogenic GC treatments.
نوع الوثيقة: article in journal/newspaper
وصف الملف: text
اللغة: English
العلاقة: https://discovery.ucl.ac.uk/id/eprint/10179580/1/ijms-24-08102.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10179580Test/
الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10179580/1/ijms-24-08102.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10179580Test/
حقوق: open
رقم الانضمام: edsbas.94BBBF77
قاعدة البيانات: BASE