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Knockdown of circ0082374 inhibits cell viability, migration, invasion and glycolysis in glioma cells by miR-326/SIRT1.
Brain Research ( IF 2.9 ) Pub Date : 2020-09-04 , DOI: 10.1016/j.brainres.2020.147108
Bin Wang 1 , Bing Li 2 , Tongguo Si 3
Affiliation  

Circular RNAs (circRNAs) play important roles in the development and treatment of glioma. However, the role and mechanism of circRNA carboxypeptidase A4 (circ0082374) in glioma are largely unknown. Forty-two glioma patients and 28 normal patients were recruited. Glioma cell lines A172 and U251 were used for functional assays. The expression levels of circ0082374, microRNA-326 (miR-326) and sirtuin 1 (SIRT1) were examined via quantitative real-time polymerase chain reaction or western blot. Cell viability, migration, invasion and glycolysis were measured via cell counting kit-8, trans-well, oxygen consumption rate and western blot, respectively. The target correlation of circ0082374/miR-326 or miR-326/SIRT1 was explored via dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. The role of circ0082374 in vivo was investigated via xenograft model. We found circ0082374 expression was elevated in glioma tissues and cells. Knockdown of circ0082374 suppressed the viability, migration, invasion and glycolysis in glioma cells. miR-326 was a target of circ0082374 and miR-326 knockdown attenuated the inhibitive role of circ0082374 silence in glioma progression. SIRT1 was a target of miR-326 and circ0082374 could promote SIRT1 expression by sponging miR-326. Silence of SIRT1 reversed the promoting effect of circ0082374 on glioma progression. Knockdown of circ0082374 reduced xenograft tumor growth by miR-326/SIRT1 in vivo. Collectively, silence of circ0082374 repressed the viability, migration, invasion and glycolysis in glioma cells by regulating miR-326 and SIRT1 in a ceRNA mechanism, providing a new mechanism for the pathogenesis of glioma.



中文翻译:

通过 miR-326/SIRT1 敲低 circ0082374 抑制胶质瘤细胞中的细胞活力、迁移、侵袭和糖酵解。

环状RNA(circRNA)在胶质瘤的发生和治疗中发挥着重要作用。然而,circRNA羧肽酶A4(circ0082374)在胶质瘤中的作用和机制在很大程度上是未知的。招募了 42 名胶质瘤患者和 28 名正常患者。神经胶质瘤细胞系 A172 和 U251 用于功能测定。通过定量实时聚合酶链反应或蛋白质印迹检测 circ0082374、microRNA-326 (miR-326) 和 Sirtuin 1 (SIRT1) 的表达水平。分别通过细胞计数试剂盒 8、trans-well、耗氧率和蛋白质印迹测量细胞活力、迁移、侵袭和糖酵解。通过双荧光素酶报告基因、RNA 免疫沉淀和下拉分析探索了 circ0082374/miR-326 或 miR-326/SIRT1 的靶标相关性。circ0082374的作用通过异种移植模型研究体内。我们发现 circ0082374 在神经胶质瘤组织和细胞中表达升高。circ0082374 的敲低抑制了胶质瘤细胞的活力、迁移、侵袭和糖酵解。miR-326 是 circ0082374 的靶标,miR-326 敲低减弱了 circ0082374 沉默在胶质瘤进展中的抑制作用。SIRT1 是 miR-326 的靶标,circ0082374 可以通过海绵 miR-326 促进 SIRT1 表达。SIRT1 的沉默逆转了 circ0082374 对胶质瘤进展的促进作用。在体内miR-326/SIRT1 敲除 circ0082374 可减少异种移植肿瘤的生长. 总的来说,circ0082374的沉默通过在ceRNA机制中调节miR-326和SIRT1来抑制胶质瘤细胞的活力、迁移、侵袭和糖酵解,为胶质瘤的发病机制提供了新的机制。

更新日期:2020-09-10
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