Circular RNA has_circ_0000034 accelerates retinoblastoma advancement through the miR-361-3p/ADAM19 axis
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Circular RNA has_circ_0000034 accelerates retinoblastoma advancement through the miR‑361‑3p/ADAM19 axis Yanhua Jiang1 · Fan Xiao1 · Lin Wang1 · Ting Wang1 · Linlin Chen1 Received: 14 May 2020 / Accepted: 14 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 (qRTPCR). 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 pulldown 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 miR361-3p 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 RB · circ_0000034 · miR-361-3p · ADAM19
Introduction Retinoblastoma (RB) is a common intraocular malignant tumor in children that originates from the retina embryonic nucleus cells [1]. Based on the preservation of children’s visual function, chemotherapy combined with adjuvant therapy has gradually become the preferred method for RB treatment [2]. However, this treatment method has side effects that can’t achieve the desired effect [3, 4]. Furthermore, some children have reached the advanced of RB at Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03886-5) contains supplementary material, which is available to authorized users. * Linlin Chen [email protected] 1
Department of Ophthalmology, The Fourth People’s Hospital of Shenyang, No. 20 Huanghe South Street, Huanggu District, Shenyang 110031, Liaoning, China
the time of diagnosis, which means that the possibility of eyeball removal is high [5]. Therefore, it is vital t
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