MicroRNA-375-3p Suppresses Upper Tract Urothelial Carcinoma Cell Migration and Invasion via Targeting Derlin-1

Jhen-Hao Jhan; Wei-Chi Hsu; Yi-Chen Lee; Wei-Ming Li; A-Mei Huang; Hui-Hui Lin; Chien-Sheng Wang; Yi-Ru Wu; Ching-Chia Li; Wen-Jeng Wu; Hung-Lung Ke

doi:10.3390/cancers14040880

MicroRNA-375-3p Suppresses Upper Tract Urothelial Carcinoma Cell Migration and Invasion via Targeting Derlin-1

Cancers (Basel). 2022 Feb 10;14(4):880. doi: 10.3390/cancers14040880.

Authors

Jhen-Hao Jhan^{1

2

3

4}, Wei-Chi Hsu^{1

5}, Yi-Chen Lee⁶, Wei-Ming Li^{1

2

7}, A-Mei Huang^{4

5

8}, Hui-Hui Lin^{1

2}, Chien-Sheng Wang^{2

4}, Yi-Ru Wu⁹, Ching-Chia Li^{1

2}, Wen-Jeng Wu^{1

2

5}, Hung-Lung Ke^{1

2

5

10}

Affiliations

¹ Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
² Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
³ Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 81267, Taiwan.
⁴ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁵ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁶ Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁷ Department of Urology, Ministry of Health and Welfare, Pingtung Hospital, Pingtung 90054, Taiwan.
⁸ Department of Biochemistry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁹ General Division, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
¹⁰ Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan.

Abstract

Little is known regarding the molecular characterization of upper tract urothelial carcinoma (UTUC). Novel therapeutic targets and prognostic predictors are imminent. In the present study, we aim to examine the oncogenic function and molecular mechanism of Derlin-1 in UTUC. Derlin-1 overexpression is significantly associated with poor prognosis in patients with UTUC. In vitro, knockdown or over-expression of Derlin-1 markedly regulated UTUC cell invasion and migration. We further discovered miR-375-3p suppresses cell invasion and migration by inversely regulating Derlin-1 and blocking EMT in UTUC cells. Taking this together, miR-375-3p functions as a tumor suppressive microRNA by directly targeting Derlin-1 and blocking epithelial-mesenchymal transition (EMT) in UTUC.

Keywords: Derlin-1; biomarkers; epithelial–mesenchymal transition (EMT); miR-375-3p; precision oncology; prognostic factor; upper tract urothelial carcinoma (UTUC).

Abstract

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