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MiR-181b suppress glioblastoma multiforme growth through inhibition of SP1-mediated glucose metabolism
Cancer Cell International ( IF 5.8 ) Pub Date : 2020-03-04 , DOI: 10.1186/s12935-020-1149-7
JianXing Yin 1 , ZhuMei Shi 1 , WenJin Wei 2 , Chenfei Lu 1 , Yutian Wei 1 , Wei Yan 1 , Rui Li 1 , JunXia Zhang 1 , YongPing You 1 , XieFeng Wang 1
Affiliation  

Glucose metabolic reprogramming is a significant hallmark of malignant tumors including GBM. Previous studies suggest that microRNAs play key roles in modulating this process in GBM cells. miR-181b acts as a tumor suppressor miRNA in influencing glioma tumorigenesis. Our previous results showed that miR-181b was down-regulated in glioma cells and tissues. The extracellular acidification rate (ECAR), colony formation assay and levels of Glut1 and PKM2 were measured to assess the glucose metabolic and proliferation changes in GBM cells overexpressing miR-181b. Immunoblotting and luciferase reporter assay were performed to confirm the expression and role of SP1 as a direct target of miR-181b. ChIP assay was used to figure out the transcriptional regulation of SP1 on Glut1 and PKM2. In vivo study was examined for the role of miR-181b in GBM cells. MiR-181b overexpression significantly reduced the glucose metabolic and colony formation ability of GBM cells. And, SP1 was confirmed as a direct target of miR-181b while upregulation of SP1 could reverse the influence of overexpression of miR-181b. Furthermore, Glut1 and PKM2 could be regulated by SP1. Finally, miR-181b could inhibit the tumor growth in vivo. Our article demonstrated the inhibitory effect of miR-181b on glucose metabolism and proliferation in GBM by suppressing SP1 expression.

中文翻译:

MiR-181b 通过抑制 SP1 介导的葡萄糖代谢来抑制多形性胶质母细胞瘤的生长

葡萄糖代谢重编程是包括 GBM 在内的恶性肿瘤的重要标志。以前的研究表明,microRNA 在调节 GBM 细胞中的这一过程中起关键作用。miR-181b 作为肿瘤抑制 miRNA 影响神经胶质瘤的发生。我们之前的结果表明 miR-181b 在胶质瘤细胞和组织中下调。测量细胞外酸化率 (ECAR)、集落形成试验以及 Glut1 和 PKM2 的水平,以评估过表达 miR-181b 的 GBM 细胞的葡萄糖代谢和增殖变化。进行免疫印迹和荧光素酶报告基因测定以确认 SP1 作为 miR-181b 的直接靶标的表达和作用。ChIP 测定用于确定 SP1 对 Glut1 和 PKM2 的转录调控。体内研究检查了 miR-181b 在 GBM 细胞中的作用。MiR-181b 过表达显着降低了 GBM 细胞的葡萄糖代谢和集落形成能力。并且,SP1 被证实是 miR-181b 的直接靶标,而 SP1 的上调可以逆转 miR-181b 过表达的影响。此外,Glut1 和 PKM2 可以受 SP1 的调节。最后,miR-181b 可以抑制体内肿瘤的生长。我们的文章通过抑制 SP1 的表达证明了 miR-181b 对 GBM 中葡萄糖代谢和增殖的抑制作用。
更新日期:2020-03-06
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