LncRNA ZFPM2-AS1 Enhances Retinoblastoma Development by Targeting the miR-3612/NT5E Signaling Axis.

Abstract

Background - Retinoblastoma (RB) is an intraocular malignancy usually observed in children. The zinc finger protein, FOG family member 2 (ZFPM2)-antisense RNA 1 (AS1), an anomalous long non-coding RNA, is detected in many cancers. This study aimed to evaluate the role and underlying mechanism of ZFPM2-AS1 in RB. Methods - ZFPM2-AS1, 5'-nucleotidase ecto (NT5E), and microRNA (miR)-3612 expression levels were determined in RB cells and tissues. Multiple experiments, including cell counting kit-8, 5'-bromo-2'-deoxyuridine, transwell, and enzyme-linked immunosorbent assays, were conducted to evaluate their effects on cell proliferation, migration, and apoptosis. Additionally, the ZFPM2-AS1/miR-3612/NT5E axis was validated using luciferase reporter, anti-AGO2 RNA immunoprecipitation, and RNA pull-down assays. Results - Overexpression of ZFPM2-AS1 and NT5E and downregulation of miR-3612 expression levels were observed in RB cells and tissues. Knockdown of ZFPM2-AS1 decreased the proliferation and migration of RB cells, while enhancing their apoptosis. The ZFPM2-AS1/miR-3612/NT5E axis was further supported by the negative correlation between miR-3612 expression levels and ZFPM2-AS1 or NT5E expression levels in RB tissues. Moreover, the miR-3612 inhibitor restored the inhibitory effect on the malignant behavior of RB cells by silencing ZFPM2-AS1. Furthermore, NT5E silencing phenocopied the effect of ZFPM2-AS1 silencing and abolished miR-3612 inhibitor-induced stimulation of the malignant behavior of RB cells. Conclusion - These results suggest that by targeting the miR-3612/NT5E axis, ZFPM2-AS1 stimulates the proliferation and migration of RB cells, while inhibiting their apoptosis. Therefore, ZFPM2-AS1 may be a promising therapeutic target associated with RB development.