Circ_0075804 Regulates the Expression of LASP1 by Targeting miR-1287-5p and Thus Affects the Biological Process of Retinoblastoma

Abstract

Purpose Increasing evidence reveals that circular RNA (circRNA) dysregulation is involved in retinoblastoma (RB) pathogenesis. To further realize the development of RB, we investigated the role and regulatory mechanism of circ_0075804 in RB. Methods Real-time quantitative PCR (RT-qPCR) and western blot were employed for expression analysis. CCK-8 assay, EdU assay, colony formation assay, flow cytometry assay and transwell assay were performed to monitor cell phenotypes. Xenograft models were established to monitor the role of circ_0075804 on tumor growth. Tumor growth was assessed by the expression of Ki67, N-cadherin, MMP2 and MMP9 via IHC assay. The predicted binding sites between miR-1287-5p and circ_0075804 or LIM and SH3 protein 1 (LASP1) were validated by dual-luciferase reporter assay. Results Upregulation of circ_0075804 and LASP1, and downregulation of miR-1287-5p were shown in RB tissues and cells. Circ_0075804 knockdown repressed RB cell growth, invasion and survival, and hindered tumor development in vivo. MiR-1287-5p was targeted by circ_0075804, and its repression largely reversed the functional effects of circ_0075804 knockdown. LASP1 was a functional target of miR-1287-5p. The inhibition of miR-1287-5p upregulation on RB cell proliferation, survival and invasion was reversed by LASP1 overexpression. Moreover, circ_0075804 knockdown weakened LASP1 expression via increasing miR-1287-5p. Conclusion Circ_0075804 promotes LASP1 expression by targeting miR-1287-5p, thus acting as a contributor to RB carcinogenesis. Highlights Circ_0075804 is overexpressed in RB. Circ_0075804 knockdown inhibits RB cell malignant phenotypes and tumor growth in vivo. Circ_0075804 regulates RB cell behaviors by targeting miR-1287-5p. MiR-1287-5p affects RB cell behaviors by binding to LASP1. Circ_0075804 regulates LASP1 expression via targeting miR-1287-5p.