微小核糖核酸-375藉由調控Derlin-1抑制上泌尿道上皮癌細胞的爬行和侵襲能力

詹鎮豪^1,2,3,4, 徐偉齊 ⁵, 李怡琛 ⁶, 李威明 ^1,2,7, 林慧惠^2,5, 黃阿梅 ^4,5,8, 吳奕儒 ⁹,
吳文正 ^1,2,5, 李經家 ^{1, 2}, 柯宏龍 ^1,2,5*

¹ 高雄醫學大學附設醫院 泌尿部; ² 高雄醫學大學 醫學院泌尿學科; ³ 高雄市立小港醫院 泌尿科;

⁴ 高雄醫學大學 醫學院臨床醫學研究所，⁵ 醫學院醫學研究所，⁶ 醫學院解剖學科;
⁷ 衛生福利部屏東醫院 泌尿科; ⁸ 高雄醫學大學 醫學院生物化學科;
⁹ 高雄醫學大學附設醫院 一般科

miR-375 suppresses upper tract urothelial carcinoma cell migration and invasion
via targeting Derlin-1

Jhen-Hao Jhan ^1,2,3,4, Wei-Chi Hsu ⁵, Yi-Chen Lee ⁶, Wei-Ming Li ^1,2,7, Hui-Hui Lin ^2,5, A-Mei Huang ^4,5,8, Yi-Ru Wu ⁹, Wen-Jeng Wu ^1,2,5, Ching-Chia Li ^{1, 2}, Hung-Lung Ke ^1,2,5*

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

Purpose:

Derlin-1 protein encoded by the DERL1 gene is located in the membrane of the endoplasmic reticulum (ER) and is responsible for unfolded protein response. Overexpression of Derlin-1 are associated with many human malignancies, so Derlin-1 have recently drawn lots of attention in the pathogenesis of cancer. In this study, we aimed to explore its role and molecular mechanism in upper tract urothelial carcinoma (UTUC).

Materials and methods:

The expression of the Derlin-1 in human UTUC specimens was examined by immunohistochemistry. We further investigated the functions and underlying mechanisms of Derlin-1 in epithelial-mesenchymal transition (EMT) by western blot, proliferation assay, wound healing assay and ECMatrix cell invasion assay in vitro.

Results:

The overexpression of Derlin-1 was significantly associated with stage, distant metastasis, recurrence and poor prognosis in patients with UTUC. Overexpression of Derlin-1 markedly promoted UTUC cell migration and invasion in vitro, and we further revealed that miR-375 negatively regulated EMT by directly targeting Derlin-1.

Conclusions:

Taken together, miR-375 may suppress UTUC cell motility and invasion via targeting Derlin1 through EMT, suggesting that Derlin-1 may serve as a potential therapeutic target and useful predictor of prognosis for patients with UTUC.