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MicroRNA-299-3p inhibits cell proliferation, motility, invasion and angiogenesis via VEGFA in upper tract urothelial carcinoma.

التفاصيل البيبلوغرافية
العنوان: MicroRNA-299-3p inhibits cell proliferation, motility, invasion and angiogenesis via VEGFA in upper tract urothelial carcinoma.
المؤلفون: Wang CS; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Lee YC; Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Jhan JH; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.; Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan., Li WM; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan.; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Chang LL; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Huang AM; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Lin HH; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Wu YR; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Hsu WC; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Ke HL; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
المصدر: The journal of gene medicine [J Gene Med] 2024 Jan; Vol. 26 (1), pp. e3616. Date of Electronic Publication: 2023 Dec 04.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Country of Publication: England NLM ID: 9815764 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-2254 (Electronic) Linking ISSN: 1099498X NLM ISO Abbreviation: J Gene Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Chichester, UK : John Wiley & Sons,
مواضيع طبية MeSH: Carcinoma, Transitional Cell*/genetics , MicroRNAs*/genetics , Urinary Bladder Neoplasms*/genetics, Humans ; Angiogenesis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism
مستخلص: Background: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different features between Eastern and Western countries. Vascular endothelial growth factor-A (VEGFA) was originally identified as a secreted signaling protein and regulator of vascular development and cancer progression. In this study, we aimed to elucidate the molecular mechanisms underlying the regulation of VEGFA by microRNA in UTUC.
Methods: VEGFA expression was evaluated by immunohistochemistry in 140 human UTUC tissue samples. Next, we assessed the regulatory relationship between VEGFA and miR-299-3p by real-time PCR, western blotting, ELISA and dual-luciferase reporter assays using two UTUC cell lines. The role of miR-299-3p/VEGFA in cell proliferation, motility, invasion, and tube formation was analyzed in vitro.
Results: High VEGFA expression was significantly associated with tumor stage, grade, distant metastasis and cancer-related death and correlated with poor progression-free and cancer-specific survival. VEGFA knockdown repressed proliferation, migration, invasion and angiogenesis in UTUC cell lines. miR-299-3p significantly reduced VEGFA protein expression and miR-299-3p overexpression inhibited VEGFA mRNA and protein expression by directly targeting its 3'-UTR. Functional studies indicated that VEGFA overexpression reversed the miR-299-3p-mediated suppression of tumor cell proliferation, migration, invasion and angiogenesis. In addition, miR-299-3p/VEGFA suppressed cellular functions in UTUC by modulating the expression of P18 and cyclin E2.
Conclusions: Our findings suggest that miR-299-3p possibly suppresses UTUC cell proliferation, motility, invasion and angiogenesis via VEGFA. VEGFA may act as a prognostic predictor, and both VEGFA and miR-299-3p could be potential therapeutic targets for UTUC.
(© 2023 John Wiley & Sons Ltd.)
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معلومات مُعتمدة: KMUH111-1M46 Kaohsiung Medical University Chung-Ho Memorial Hospital; 109-2314-B-037-105-MY3 National Science and Technology Council; 111-2811-B-037-021 National Science and Technology Council
فهرسة مساهمة: Keywords: VEGFA; miR-299-3p; prognosis; upper tract urothelial carcinoma
المشرفين على المادة: 0 (MicroRNAs)
0 (MIRN299 microRNA, human)
0 (Vascular Endothelial Growth Factor A)
0 (VEGFA protein, human)
تواريخ الأحداث: Date Created: 20231205 Date Completed: 20240205 Latest Revision: 20240205
رمز التحديث: 20240205
DOI: 10.1002/jgm.3616
PMID: 38049938
قاعدة البيانات: MEDLINE
الوصف
تدمد:1521-2254
DOI:10.1002/jgm.3616