Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, China.
Department of Pathology, Xiangya Medical School of Central South University & Xiangya Hospital Central South University, Changsha, China.
CNS Neurosci Ther. 2020 Mar;26(3):319-331. doi: 10.1111/cns.13273. Epub 2019 Dec 23.
Accumulating evidence has highlighted the correlation between microRNAs (miRNAs) and the progression of glioma. However, the role of miR cluster MC-let-7a-1 ~ let-7d in glioma remains elusive. Thus, the current study aimed to investigate the effect of miR cluster MC-let-7a-1 ~ let-7d on glioma progression.
Microarray data analysis provided data indicating the involvement of miR cluster MC-let-7a-1 ~ let-7d in glioma via STAT3. The expression of let-7a-1, let-7d, let-7f-1, and miR cluster MC-let-7a-1 ~ let-7d was diminished in the glioma tissues and the cell lines. Additionally, our results revealed that STAT3 was a target gene of let-7d, let-7a-1, and let-7f-1, which was further verified by the dual-luciferase reporter gene assay. Moreover, STAT3 expression was negatively mediated by let-7a-1, let-7d, and let-7f-1. Up-regulated miR cluster MC-let-7a-1 ~ let-7d or silenced STAT3 suppressed cell proliferation but accelerated cell apoptosis and autophagy. Moreover, restrained tumor growth was identified in the nude mice treated with miR cluster MC-let-7a-1 ~ let-7d mimics or STAT3 siRNA.
Taken together, the miR cluster MC-let-7a-1 ~ let-7d promotes glioma cell autophagy and apoptosis by repressing STAT3. The current study highlights the potential of the miR cluster MC-let-7a-1 ~ let-7d as biomarkers and promising treatment strategies for glioma.
越来越多的证据强调了 microRNAs(miRNAs)与神经胶质瘤进展之间的相关性。然而,miR 簇 MC-let-7a-1let-7d 在神经胶质瘤中的作用仍不清楚。因此,本研究旨在探讨 miR 簇 MC-let-7a-1let-7d 对神经胶质瘤进展的影响。
通过 STAT3 对 miR 簇 MC-let-7a-1let-7d 在神经胶质瘤中的作用进行了微阵列数据分析。在神经胶质瘤组织和细胞系中,let-7a-1、let-7d、let-7f-1 和 miR 簇 MC-let-7a-1let-7d 的表达减少。此外,我们的研究结果表明 STAT3 是 let-7d、let-7a-1 和 let-7f-1 的靶基因,这进一步通过双荧光素酶报告基因检测得到证实。此外,let-7a-1、let-7d 和 let-7f-1 负调控 STAT3 的表达。上调的 miR 簇 MC-let-7a-1let-7d 或沉默 STAT3 抑制细胞增殖,加速细胞凋亡和自噬。此外,在裸鼠中,用 miR 簇 MC-let-7a-1let-7d 模拟物或 STAT3 siRNA 处理可抑制肿瘤生长。
综上所述,miR 簇 MC-let-7a-1let-7d 通过抑制 STAT3 促进神经胶质瘤细胞自噬和凋亡。本研究强调了 miR 簇 MC-let-7a-1let-7d 作为神经胶质瘤生物标志物和有前途的治疗策略的潜力。