微小核糖核酸-214藉由調控CSF-1影響上泌尿道上皮癌的能力
徐偉齊¹、黃阿梅^{1, 2, 3}、李威明^{1, 4, 5, 6}、李怡琛⁷、張玲麗^{1, 8}、林慧惠¹、吳文正^{1, 4, 5}、李經家^{4, 5}、
連培因⁹、柯宏龍^{1, 4, 5}*
高雄醫學大學 醫學院醫學研究所 ¹，臨床醫學研究所 ²，醫學院醫學研究所 生物化學科 ³ ; 高雄醫學大學附設醫院 泌尿科 ⁴ ; 高雄醫學大學 醫學院醫學研究所 泌尿學科 ⁵ ; 衛生福利部屏東醫院泌尿科 ⁶ ; 高雄醫學大學 醫學院醫學研究所 解剖學科 ⁷，微生物與免疫學科 ⁸；

高雄醫學大學附設醫院 病理科 ⁹

MicroRNA-214 in upper tract urothelial carcinoma and its effect on tumor cell behaviour by targeting CSF-1
Wei-Chi Hsu ¹, A-Mei Huang ^{1, 2, 3}, Wei-Ming Li ^{1, 4, 5, 6} , Yi-Chen Lee ⁷, Lin-Li Chang ^{1, 8}, Hui-Hui Lin ¹, Wen-Jeng Wu ^{1, 4, 5}, Ching-Chia Li ^{4, 5}, Peir-In Liang ⁹, Hung-Lung Ke ^{1, 4, 5} *

¹ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ² Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ³ Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ⁴ Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. ⁵ Department of Urology, 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 Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ⁸ Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ⁹ Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

 

Purpose: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different feature between Eastern and Western countries. Colony-stimulating factor-1 (CSF-1) is a homodimeric glycoprotein that is involved in multiple biological functions and also be reported that is aberrantly expressed in several human cancers. MiR-214 governs both tumorigenic and tumor suppressive functions. We aimed to elucidate the molecular mechanism underlying the regulation of CSF-1 by miR-214 in UTUC.
Materials and methods: CSF-1 expression was evaluated by immunohistochemistry and miR-214 expression was analyzed by real-time qPCR in patients with UTUC. We demonstrated that the regulatory relationship between CSF-1 and miR-214 by ELISA and dual luciferase reporter assay. The role of the miR-214/CSF-1 pathway in proliferation, motility and invasion was analyzed in vitro.

Results: CSF-1 expression was observed to be higher in UTUC than paired tumor adjacent normal tissues. High CSF-1 expression was correlated with poor disease-free survival (P = 0.008) and cancer-specific survival (P = 0.001). A reverse correlation between CSF-1 and miR-214 was found in UTUC tissues. MiR-214 inhibited CSF-1 mRNA and protein expression by directly targeting its 3'-UTR. Using nuclear and cytoplasmic extraction, miR-214 mainly reduced nuclear CSF-1 expression in UTUC cells. The functional studies indicated that overexpression miR-214 or knock-down CSF-1 repressed tumor cell proliferation, migration and invasion. Notably, miR-214 reduced phospho-AKT^ser473 activity in vitro.

Conclusion: These findings suggest that miR-214 may suppress UTUC cell proliferation, motility and invasion by targeting CSF-1.