CircDHDDS/miR-361-3p/WNT3A Axis Promotes the Development of Retinoblastoma by Regulating Proliferation, Cell Cycle, Migr
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ORIGINAL PAPER
CircDHDDS/miR‑361‑3p/WNT3A Axis Promotes the Development of Retinoblastoma by Regulating Proliferation, Cell Cycle, Migration, and Invasion of Retinoblastoma Cells Hongjun Wang1 · Mingze Li2 · Haibin Cui3 · Xiangyuan Song2 · Qian Sha2 Received: 3 January 2020 / Revised: 9 August 2020 / Accepted: 13 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Retinoblastoma (RB) is a common intraocular malignant tumor. The growing evidence has reported that circular RNAs (circRNAs) play critical roles in RB development. Therefore, the purpose of the study is to investigate the regulatory mechanism of circDHDDS in RB. The real-time quantitative polymerase chain reaction (RT-qPCR) assay was used to quantify the expression levels of circDHDDS, miR-361-3p, and WNT3A in RB tissues and cells (RPCs, Y-79, and WERI-Rb-1). The proliferation and cell cycle of RB cells were assessed by colony formation assay and flow cytometry assays, respectively. The migration and invasion of RB cells were measured by transwell assay. The protein expression levels of Nectin-3 (CD113), SOX2, Nanog, and WNT3A were measured by Western blot assay. The functional targets of circDHDDS and miR-361-3p were predicted by bioinformatics databases, and the dual-luciferase reporter assay was used to confirm the interaction relationship between miR-361-3p and circDHDDS or WNT3A. The functional role of circDHDDS silencing in vivo was evaluated by xenograft experiment. We found that circDHDDS was overexpressed in RB tissues and cells compared with normal retinas tissues and retinal pigment epithelial cells, correspondingly. Furthermore, silencing of circDHDDS impeded proliferation, migration, invasion, and induced cell cycle arrest in vitro, which were abolished by knockdown of miR-361-3p. The in vivo experiments also suggested that tumor growth was inhibited by knockdown of circDHDDS. Moreover, we also found that miR-361-3p specifically bound to WNT3A, and overexpression of miR-361-3p suppressed RB development by decreasing WNT3A expression. Summarily, circDHDDS, a molecule sponge of miR-361-3p, regulated the expression of WNT3A. Therefore, circDHDDS/miR-361-3p/WNT3A axis stimulated the development of RB by regulation of proliferation, cell cycle program, migration, and invasion of RB cells. Keywords Circular RNA · circDHDDS · miR-361-3p · WNT3A · RB Abbreviations RB Retinoblastoma circRNA Circular RNA RT-qPCR Real-time quantitative polymerase chain reaction
* Qian Sha [email protected] 1
Department of Medical Administration, Shanghai Pudong Hospital, Shanghai, China
2
Department of Ophthalmology, Shanghai Pudong Hospital, Shanghai, China
3
Department of Ophthalmology, Heilongjiang Eye Hospital, Harbin, Heilongjiang, China
Introduction Retinoblastoma (RB), originating from infants’ retinal immature cells, is a rare malignant tumor of the retina [1]. According to the report, mortality of 9% can be reduced by efficient management of RB patients [2], thus early diagnosis and effective therapeutic
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