Circ_0075804 promotes the malignant behaviors of retinoblastoma cells by binding to miR-138-5p to induce PEG10 expression.

Abstract

It has been gradually recognized that circular RNAs (circRNAs) are important modulators in multiple malignancies. Here, we analyzed the function of circ_0075804 and explored its associated mechanism in regulating retinoblastoma (RB) progression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were utilized to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell counting kit-8 (CCK8) assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to verify intermolecular target relations. Xenograft tumor model was used to analyze the role of circ_0075804 in tumor growth in vivo. Circ_0075804 expression was markedly up-regulated in RB tissues and cell lines. Circ_0075804 knockdown restrained the proliferation, migration and invasion whereas promoted the apoptosis of RB cells. Circ_0075804 acted as a molecular sponge for microRNA-138-5p (miR-138-5p), and circ_0075804 silencing-induced effects were partly reversed by miR-138-5p knockdown in RB cells. MiR-138-5p interacted with the 3' untranslated region (3'UTR) of paternally expressed 10 (PEG10). Circ_0075804 positively regulated PEG10 level by sponging miR-138-5p in RB cells. PEG10 overexpression largely overturned miR-138-5p overexpression-mediated effects in RB cells. Circ_0075804 knockdown blocked xenograft tumor growth in vivo. Circ_0075804 promoted RB progression via miR-138-5p-dependent regulation of PEG10, which provided new insight in RB therapy.