lncRNA ZFPM2-AS1 promotes retinoblastoma progression by targeting microRNA miR-511-3p/paired box protein 6 (PAX6) axis

Long non-coding RNAs (lncRNAs) have been shown to play crucial roles in retinoblastoma progression. In this study, we aimed to investigate the mechanism of lncRNA ZFPM2-AS1 (ZFPM2-AS1) in retinoblastoma progression. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting assays were performed to determine the expression of lncRNA, microRNA (miRNA), mRNA, and protein. The changes in cell proliferation, apoptosis, and cell migration were assessed by functional experiments. The interaction between ZFPM2-AS1, miR-511-3p, and paired box protein 6 (PAX6) was confirmed by a luciferase assay. Our study found that ZFPM2-AS1 and PAX6 were upregulated, whereas miR-511-3p was downregulated in retinoblastoma. ZFPM2-AS1 inhibition decreased the viability and migration of retinoblastoma cells. We also found that ZFPM2-AS1 targets miR-511-3p to upregulate PAX6 in Y79 and SO-RB50 cells. Moreover, we demonstrated that inhibiting miR-511-3p reversed the negative effects of silencing ZFPM2-AS1 and PAX6 on retinoblastoma cell viability and migration. In conclusion, retinoblastoma development is regulated by the ZFPM2-AS1/511-3p/PAX6 axis.

长链非编码RNA（long non-coding RNAs，lncRNAs）已被证实可在视网膜母细胞瘤的进展过程中发挥关键调控作用。本研究旨在探究长链非编码RNA ZFPM2-AS1（ZFPM2-AS1）在视网膜母细胞瘤进展中的作用机制。本研究采用定量逆转录聚合酶链反应（quantitative reverse transcriptase polymerase chain reaction，qRT-PCR）与蛋白质印迹法（Western blotting）实验，检测lncRNA、微小RNA（microRNA，miRNA）、信使RNA（messenger RNA，mRNA）及蛋白的表达水平；通过功能实验评估细胞增殖、凋亡与细胞迁移能力的变化。利用荧光素酶报告实验验证ZFPM2-AS1、miR-511-3p与配对盒蛋白6（paired box protein 6，PAX6）之间的相互作用。本研究结果显示，在视网膜母细胞瘤中，ZFPM2-AS1与PAX6呈高表达状态，而miR-511-3p呈低表达状态。抑制ZFPM2-AS1可降低视网膜母细胞瘤细胞的存活率与迁移能力。本研究还证实，在Y79与SO-RB50细胞系中，ZFPM2-AS1通过靶向调控miR-511-3p，进而上调PAX6的表达。此外，本研究证实，抑制miR-511-3p可逆转敲低ZFPM2-AS1或PAX6对视网膜母细胞瘤细胞存活率与迁移能力产生的负面效应。综上，ZFPM2-AS1/miR-511-3p/PAX6调控轴可参与调控视网膜母细胞瘤的发生发展。