ABSTRACT

Circular RNAs (circRNAs) exert a critical effect on tumorigenesis and development. Our research aimed to clarify the function and underlying mechanism of circ_0060937 inNSCLC. The concentrations of circ_0060937, miR-195-5p and high-mobility group box 3 (HMGB3) were monitored via qRT-PCR and western blot assays. Additionally, cell proliferation, apoptosis, migration and invasion were assessed using CCK-8, colony formation, flow cytometry and transwell assays. Glycolysis was evaluated via detecting glucose uptake and lactate product. The association between miR-195-5p and circ_0060937/HMGB3 were validated using dual-luciferase reporter, RNA pull-down and RIP assays. Furthermore,in vivo experiment was performed to analyze tumorigenesis.Circ_0060937 and HMGB3 levels were elevated, whereas miR-195-5p level was dropped in NSCLC. Circ_0060937 down-regulation restrainedNSCLC cell proliferation, migration, invasion and glycolysis, and triggered apoptosis. Knockdown of circ_0060937 restrained NSCLC development via absorbing miR-195-5p. Circ_0060937 silencing inhibited NSCLC progression by mediating HMGB3. Besides, circ_0060937 depletion suppressed tumor growth in vivo.Circ_0060937 knockdown hindered NSCLC development and glycolysis via regulating miR-195-5p/HMGB3 pathway.

摘要

环状 RNA (circRNA) 对肿瘤的发生和发展发挥关键作用。我们的研究旨在阐明circ_0060937在NSCLC中的功能和潜在机制。通过 qRT-PCR 和蛋白质印迹分析监测 circ_0060937、miR-195-5p 和高迁移率组框 3 (HMGB3) 的浓度。此外，使用 CCK-8、集落形成、流式细胞术和 transwell 测定法评估细胞增殖、凋亡、迁移和侵袭。通过检测葡萄糖摄取和乳酸产物来评估糖酵解。使用双荧光素酶报告基因、RNA pull-down 和 RIP 分析验证了 miR-195-5p 和 circ_0060937/HMGB3 之间的关联。此外，在体内 进行实验分析肿瘤发生。Circ_0060937和HMGB3水平升高，而miR-195-5p水平在NSCLC中下降。Circ_0060937 下调抑制 NSCLC 细胞增殖、迁移、侵袭和糖酵解，并引发细胞凋亡。circ_0060937 的敲除通过吸收 miR-195-5p 抑制了 NSCLC 的发展。Circ_0060937 沉默通过介导 HMGB3 抑制 NSCLC 进展。此外，circ_0060937 缺失抑制 了体内肿瘤生长。Circ_0060937 敲低通过调节 miR-195-5p/HMGB3 通路阻碍了 NSCLC 的发展和糖酵解。