Circular RNA has_circ_0000034 accelerates retinoblastoma advancement through the miR-361-3p/ADAM19 axis

Abstract

Retinoblastoma (RB) is an intraocular malignancy that mainly occurs in infants and young children under 5 years of age. Circular RNA hsa_circ_0000034 (circ_0000034) was reported to be upregulated in RB tissues. Nevertheless, the function and mechanism of circ_0000034 in RB are unclear. Expression of circ_0000034, microRNA-361-3p (miR-361-3p), and a disintegrin and metalloproteinase 19 (ADAM19) was examined via quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, migration, invasion, and apoptosis were determined though Cell Counting Kit-8 (CCK-8), transwell, or flow cytometry assays. Caspase-3 activity was detected using a caspase-3 activity assay kit. Some protein levels were examined using Western blot analysis. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay were performed to verify the relationship between circ_0000034 or ADAM19 and miR-361-3p. The function of circ_0000034 in vivo was confirmed via animal experiment. We verified that circ_0000034 expression was elevated in RB tissues and cells. Circ_0000034 silencing reduced RB growth in vivo, repressed viability, migration, invasion, and EMT, and induced apoptosis of RB cells in vitro. Circ_0000034 acted as a sponge for miR-361-3p, which targeted ADAM19 in RB cells. Furthermore, the inhibition of miR-361-3p restored circ_0000034 knockdown-mediated impacts on viability, migration, invasion, apoptosis, and EMT of RB cells. Moreover, ADAM19 overexpression abolished the influence of miR-361-3p mimic on viability, migration, invasion, apoptosis, and EMT of RB cells. Circ_0000034 expedited RB progression through upregulating ADAM19 via sponging miR-361-3p, which indicated that circ_0000034 might a target for RB therapy.

Keywords: ADAM19; RB; circ_0000034; miR-361-3p.