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

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.HighlightsCirc_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.