ABSTRACT

The involvement of propofol and circular RNAs (circRNAs) in lung cancer progression has been identified. However, the relationship between propofol and circRNAs as well as the underlying molecular mechanisms on lung cancer development remain unclear. Cell viability, migration and invasion were measured by cell counting kit-8 assay, 5-bromo-2-deoxyuridine (BrdU) and transwell assay. Glycolytic metabolism was calculated by measuring the glucose consumption, lactate production and extracellular acidification. Western blot was used to detect the protein of glucose transporter 1 (GLUT1), glycolysis enzymes, and forkhead box M1 (FOXM1). The expression of circRNA transcriptional adaptor 2A (circTADA2A), microRNA (miR)-455-3p and FOXM1 mRNA was detected by quantitative real-time polymerase chain reaction. The interaction between miR-455-3p and circTADA2A or FOXM1 was analyzed using the dual-luciferase reporter assay. Murine xenograft model was established to perform in vivo experiments. We found propofol treatment alleviated lung cancer cell proliferation, migration, invasion and aerobic glycolysis in vitro as well as inhibited tumor growth in vivo. Propofol decreased the level of circTADA2A and exerted anti-tumor effects by regulating circTADA2A. MiR-455-3p directly interacted with circTADA2A and FOXM1 in lung cancer cells, and circTADA2A could regulate FOXM1 expression by binding to miR-455-3p. Subsequently, rescue assay showed that propofol inhibited cell proliferation, migration, invasion and aerobic glycolysis by regulating circTADA2A/miR-455-3p/FOXM1 axis in lung cancer. Collectively, propofol suppressed cell carcinogenesis and aerobic glycolysis by regulating circTADA2A/miR-455-3p/FOXM1 axis in lung cancer, providing an effective clinical implication for propofol to prevent the development of lung cancer.

摘要

丙泊酚和环状 RNA (circRNAs) 在肺癌进展中的参与已被确定。然而，丙泊酚和circRNAs之间的关系以及肺癌发生发展的潜在分子机制仍不清楚。通过细胞计数试剂盒-8 测定、5-溴-2-脱氧尿苷 (BrdU) 和 transwell 测定测量细胞活力、迁移和侵袭。通过测量葡萄糖消耗、乳酸产生和细胞外酸化来计算糖酵解代谢。Western blot检测葡萄糖转运蛋白1（GLUT1）、糖酵解酶和叉头盒M1（FOXM1）蛋白。通过定量实时聚合酶链反应检测circRNA转录接头2A（circTADA2A）、microRNA（miR）-455-3p和FOXM1 mRNA的表达。使用双荧光素酶报告基因检测分析了 miR-455-3p 和 circTADA2A 或 FOXM1 之间的相互作用。建立小鼠异种移植模型以执行 in 体内实验。我们发现丙泊酚治疗在体外减轻了肺癌细胞的增殖、迁移、侵袭和有氧糖酵解，并在体内抑制了肿瘤生长. 丙泊酚通过调节 circTADA2A 降低 circTADA2A 水平并发挥抗肿瘤作用。MiR-455-3p 直接与肺癌细胞中的 circTADA2A 和 FOXM1 相互作用，circTADA2A 可以通过与 miR-455-3p 结合来调节 FOXM1 的表达。随后，救援实验表明丙泊酚通过调节肺癌中的circTADA2A/miR-455-3p/FOXM1轴来抑制细胞增殖、迁移、侵袭和有氧糖酵解。总的来说，丙泊酚通过调节肺癌中的circTADA2A/miR-455-3p/FOXM1轴来抑制细胞癌变和有氧糖酵解，为丙泊酚预防肺癌的发展提供了有效的临床意义。