微小核糖核酸-299-3p藉由調控VEGFA影響上泌尿道上皮癌細胞的增生爬行

和侵襲能力
王建勝1, 2、徐偉齊3、李怡琛4, 5、李威明2, 3, 4, 6、張玲麗4, 7、黃阿梅1, 8、林慧惠2、吳文正2, 3, 4
李經家2, 3、柯宏龍2, 3, 4, 9*
高雄醫學大學 臨床醫學研究所 1 ; 高雄醫學大學附設醫院 泌尿科 2 ; 高雄醫學大學 醫學系
泌尿學科 3 醫學研究所 4,解剖學科 5 ; 衛生福利部屏東醫院泌尿科 6 ;
高雄醫學大學 微生物與免疫學科 7;生物化學科 8 ; 高雄市立大同醫院 泌尿科 9

MiR-299-3p Inhibits Cell Proliferation, Motility and Invasion through VEGFA in Upper Tract Urothelial Carcinoma
Chien-Sheng Wang 1, 2, Wei-Chi Hsu 3, Yi-Chen Lee 4, 5, Wei-Ming Li 2, 3, 4, 6, Lin-Li Chang 4, 7,
A-Mei Huang 1, 8, Hui-Hui Lin 2, Wen-Jeng Wu 2, 3, 4, Ching-Chia Li 2, 3, Hung-Lung Ke 2, 3, 4, 9 *

1 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 3 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 5 Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 6 Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan. 7 Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 8 Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 9 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

 

Purpose: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different feature between Eastern and Western countries. Vascular endothelial growth factor-A (VEGFA) was originally shown to be secreted signaling protein as well as a regulator of vascular development and cancer progression. MiR-299-3p governs tumor suppressive functions in several tumors. We aimed to elucidate the molecular mechanism underlying the regulation of VEGFA by miR-299-3p in UTUC.
Materials and methods: VEGFA expression was evaluated by immunohistochemistry in one hundred and forty human UTUC tissues. We demonstrated that the regulatory relationship between VEGFA and miR-299-3p by real-time PCR, western blot and dual luciferase reporter assay. The role of the miR-299-3p/VEGFA pathway in proliferation, motility and invasion was analyzed in vitro.

Results: VEGFA high expression is significantly associated to stage (P= 0.005), grade (P= 0.004), distant metastasis (P= 0.003), and cancer death (P= 0.001). High VEGFA expression was correlated with poor progression-free survival (P= 0.001) and cancer-specific survival (P< 0.001). Knock-down VEGFA repressed UTUC cell proliferation, migration and invasion. MiR-299-3p overexpression inhibited VEGFA protein expression by directly targeting its 3'-UTR. The functional studies indicated that VEGFA overexpression reversed the miR-299-3p reduced tumor cell proliferation, migration and invasion.

Conclusion: These findings suggest that miR-299-3p may suppress UTUC cell proliferation, motility and invasion by targeting VEGFA.

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    台灣泌尿科醫學會
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    2022-06-07 09:52:18
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