Emerging evidences indicated that long non-coding RNAs (LncRNAs) regulated the pathogenesis of retinoblastoma (RB). However, up until now, the role of LncRNA Linc-PINT in the regulation of RB progression is still largely unknown. The present study identified LncRNA Linc-PINT as a tumor suppressor to hinder RB development by regulating miR-523-3p/Dickkopf-1 (DKK1) axis. Mechanistically, Linc-PINT was low-expressed, while miR-523-3p was high-expressed in RB cells, compared to the normal retinal epithelial cells (ARPE-19). Further gain- and loss-function experiments verified that both upregulation of Linc-PINT and miR-523-3p downregulation slowed down cell growth, invasion and migration, and promoted cell apoptosis in RB cells, but Linc-PINT ablation and miR-523-3p overexpression promoted malignant phenotypes in RB cells. In addition, the dual-luciferase reporter gene system and RNA pull-down assay validated that Linc-PINT positively regulated DKK1 expressions by sponging miR-523-3p, and Linc-PINT inhibited RB progression by regulating miR-523-3p/DKK1 axis. Functionally, we found that both miR-523-3p overexpression and DKK1 silence abrogated the anti-cancer effects of overexpressed Linc-PINT on RB cells. Finally, Linc-PINT inhibited tumorigenicity of RB cells in xenograft mice models. In general, analysis of the data suggested that Linc-PINT inhibited miR-523-3p to upregulate DKK1, resulting in the inhibition of RB, and we demonstrated that Linc-PINT and miR-523-3p could be utilized as potential diagnostic and therapeutic biomarkers for RB in clinic.

新兴证据表明，长非编码RNA（LncRNA）调控视网膜母细胞瘤（RB）的发病机理。然而，直到现在，LncRNA Linc-PINT在调节RB进程中的作用仍是未知的。本研究通过调节miR-523-3p / Dickkopf-1（DKK1）轴，将LncRNA Linc-PINT鉴定为抑制RB发育的肿瘤抑制因子。从机制上讲，与正常视网膜上皮细胞（ARPE-19）相比，RB细胞中的Linc-PINT表达低，而miR-523-3p的表达较高。进一步的增益和损失功能实验证实，Linc-PINT的上调和miR-523-3p的下调都减慢了RB细胞的细胞生长，侵袭和迁移，并促进了细胞凋亡，但是Linc-PINT消融和miR-523- 3p过表达促进了RB细胞的恶性表型。此外，双荧光素酶报告基因系统和RNA下拉测定法验证了Linc-PINT可以通过刺激miR-523-3p来积极调节DKK1的表达，而Linc-PINT可以通过调节miR-523-3p / DKK1轴来抑制RB的进展。在功能上，我们发现miR-523-3p过表达和DKK1沉默都消除了过表达的Linc-PINT对RB细胞的抗癌作用。最后，Linc-PINT抑制异种移植小鼠模型中RB细胞的致瘤性。通常，对数据的分析表明，Linc-PINT抑制miR-523-3p上调DKK1，从而导致RB的抑制，并且我们证明了Linc-PINT和miR-523-3p可以用作潜在的诊断和治疗方法临床中RB的生物标志物。Linc-PINT通过调节miR-523-3p / DKK1轴来抑制RB的进展。在功能上，我们发现miR-523-3p过表达和DKK1沉默都消除了过表达的Linc-PINT对RB细胞的抗癌作用。最后，Linc-PINT抑制异种移植小鼠模型中RB细胞的致瘤性。通常，对数据的分析表明，Linc-PINT抑制miR-523-3p上调DKK1，从而导致RB的抑制，并且我们证明了Linc-PINT和miR-523-3p可以用作潜在的诊断和治疗方法临床中RB的生物标志物。Linc-PINT通过调节miR-523-3p / DKK1轴来抑制RB的进展。在功能上，我们发现miR-523-3p过表达和DKK1沉默都消除了过表达的Linc-PINT对RB细胞的抗癌作用。最后，Linc-PINT抑制异种移植小鼠模型中RB细胞的致瘤性。通常，对数据的分析表明，Linc-PINT抑制miR-523-3p上调DKK1，从而导致RB的抑制，并且我们证明了Linc-PINT和miR-523-3p可以用作潜在的诊断和治疗方法临床中RB的生物标志物。