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LncRNA SNHG3/miRNA-151a-3p/RAB22A 轴调控骨肉瘤的侵袭和迁移。

LncRNA SNHG3/miRNA-151a-3p/RAB22A axis regulates invasion and migration of osteosarcoma.

机构信息

Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China.

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.

出版信息

Biomed Pharmacother. 2019 Apr;112:108695. doi: 10.1016/j.biopha.2019.108695. Epub 2019 Feb 20.

Abstract

To elucidate the potential function of lncRNA SNHG3 in the development of osteosarcoma. Quantitative real-time polymerase chain reaction was conducted for detection of SNHG3, miRNA-151a-3p and RAB22 A in osteosarcoma tissues and cells. Receiver operating characteristic curve was introduced to analyze the diagnostic potential of SNHG3 in osteosarcoma. Correlation between SNHG3 expression and the overall survival of osteosarcoma patients was evaluated using Kaplan-Meier method. Invasive and migratory potentials of osteosarcoma cells were examined by Transwell assay. Furthermore, dual-luciferase reporter gene assay, RNA-pull down and RIP assay were used to verify the binding of SNHG3/RAB22 A to miRNA-151a-3p. The function of SNHG3/miRNA-151a-3p/RAB22 A axis in osteosarcoma was finally confirmed by rescue experiments. SNHG3 and RAB22 A were highly expressed in osteosarcoma patients, while miRNA-151a-3p was lowly expressed. The overall survival of osteosarcoma patients with high expression of SNHG3 was shorter than those with low expression. SNHG3 overexpression markedly promoted invasive and migratory potentials of osteosarcoma cells. Through dual-luciferase reporter gene assay, both SNHG3 and RAB22 A could bind to miRNA-151a-3p. RAB22 A expression was positively regulated by SNHG3, but negatively regulated by miRNA-151a-3p. Finally, rescue experiments confirmed that RAB22 A overexpression could reverse the promotive effects of miRNA-151a-3p knockdown on invasive and migratory potentials of osteosarcoma cells. SNHG3 is highly expressed in osteosarcoma, and promotes the invasive and migratory potentials of osteosarcoma cells by absorbing miRNA-151a-3p to upregulate RAB22 A expression.

摘要

为了阐明 lncRNA SNHG3 在骨肉瘤发展中的潜在功能。采用定量实时聚合酶链反应检测骨肉瘤组织和细胞中的 SNHG3、miRNA-151a-3p 和 RAB22A。引入受试者工作特征曲线分析 SNHG3 在骨肉瘤中的诊断潜力。采用 Kaplan-Meier 法评估 SNHG3 表达与骨肉瘤患者总生存率的相关性。通过 Transwell 测定法检测骨肉瘤细胞的侵袭和迁移能力。此外,还使用双荧光素酶报告基因检测、RNA 下拉和 RIP 测定来验证 SNHG3/RAB22A 与 miRNA-151a-3p 的结合。最后通过挽救实验证实 SNHG3/miRNA-151a-3p/RAB22A 轴在骨肉瘤中的作用。SNHG3 和 RAB22A 在骨肉瘤患者中高表达,而 miRNA-151a-3p 低表达。SNHG3 高表达的骨肉瘤患者的总生存率短于 SNHG3 低表达的患者。SNHG3 过表达显著促进骨肉瘤细胞的侵袭和迁移能力。通过双荧光素酶报告基因检测,SNHG3 和 RAB22A 均可与 miRNA-151a-3p 结合。RAB22A 的表达受 SNHG3 的正向调节,受 miRNA-151a-3p 的负向调节。最后,挽救实验证实 RAB22A 过表达可以逆转 miRNA-151a-3p 敲低对骨肉瘤细胞侵袭和迁移能力的促进作用。SNHG3 在骨肉瘤中高表达,通过吸收 miRNA-151a-3p 来上调 RAB22A 表达,促进骨肉瘤细胞的侵袭和迁移能力。

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