Department of General Surgery, Children's Hospital Affiliated to Soochow University, Suzhou, China.
Department of General Surgery, Anhui Provincial Children's Hospital, Hefei, China.
Neurochem Res. 2024 Nov;49(11):3060-3068. doi: 10.1007/s11064-024-04225-6. Epub 2024 Aug 7.
Circular RNAs (circRNAs) are involved in the neuroblastoma (NB) development. Objectie: The study aimed to determine the biological behaviors of circ_0001361 and explore its underlying mechanism in NB.
The circ_0001361, miR-490-5p, and IGF2 levels were measured using quantitative real-time polymerase chain reaction. Cellular processes were analyzed using MTT assay or fluorescence-activated cell sorting (FACS). Phosphorylated (p)-PI3K, p-AKT, Bax, and caspase-3 were tested by western blot. Dual-luciferase reporter analysis together with RNA pull-down analysis were utilized to evaluate the correlation of miR-490-5p and circ_0001361 or IGF2.
The results in this study illustrated that an elevation of circ_0001361 levels was observed in NB. Depletion of circ_0001361 suppressed the viability but facilitated apoptosis of NB cells. Circ_0001361 sponged miR-490-5p, which targeted to regulate IGF2. Inhibition of miR-490-5p rescued the effect induced by circ_0001361 knockdown, while deletion of IGF2 rescued the effect induced by the miR-490-5p inhibitor.
In summary, a loss of circ_0001361 inhibited NB progression via targeting the miR-490-5p/IGF2 axis, suggesting that circ_0001361 may be a novel therapeutical target of NB.
环状 RNA(circRNAs)参与神经母细胞瘤(NB)的发展。目的:本研究旨在确定 circ_0001361 的生物学行为,并探讨其在 NB 中的潜在机制。
采用实时定量聚合酶链反应检测 circ_0001361、miR-490-5p 和 IGF2 的水平。采用 MTT 检测或荧光激活细胞分选(FACS)分析细胞过程。采用 Western blot 检测磷酸化(p)-PI3K、p-AKT、Bax 和 caspase-3。利用双荧光素酶报告分析和 RNA 下拉分析评估 miR-490-5p 与 circ_0001361 或 IGF2 的相关性。
本研究结果表明,NB 中 circ_0001361 水平升高。circ_0001361 耗竭抑制 NB 细胞的活力,但促进其凋亡。circ_0001361 吸附 miR-490-5p,靶向调节 IGF2。抑制 miR-490-5p 可挽救 circ_0001361 敲低引起的作用,而 IGF2 缺失可挽救 miR-490-5p 抑制剂引起的作用。
总之,circ_0001361 的缺失通过靶向 miR-490-5p/IGF2 轴抑制 NB 进展,提示 circ_0001361 可能是 NB 的一种新的治疗靶点。