Department of Neurosurgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):2870-2879. doi: 10.26355/eurrev_201904_17565.
Previous studies showed that miR-770 expression was deregulated in many tumors. However, the effect of miR-770 function on glioma remains as a mystery. The present study aimed to explore its expression, cellular function and clinic features in glioma.
We analyzed RNA sequencing data to explore abnormally expressed miRNAs in glioma. Glioma tissue specimens and their matched normal tissues were collected to test miR-770 expression using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis. The correlation between miR-770 and the clinicopathological factors and the prognostic value of miR-770 was statistically analyzed. We then investigated alterations in a series of cancer-related phenotypes, including cell viability, apoptosis, colony formation and metastasis capacities. Western blot analysis was performed to examine the expression changes of EMT-related proteins and PI3K/Akt signaling pathway proteins.
We identified a novel glioma-related miRNA miR-770, which was significantly down-regulated in human glioma tissues. The results of RT-PCR further showed that miR-770 expression was significantly down-regulated in both glioma tissues and cell lines. Furthermore, decreased miR-770 expression was significantly associated with advanced WHO grade, KPS score and shorter five-year overall survival. Then, functional assays indicated that overexpression of miR-770 suppressed proliferation, migration, invasion and EMT pathway, and induced the apoptosis of glioma cells in vitro. Moreover, we further illustrated that the up-regulation of miR-770 suppressed the PI3K-AKT signaling pathway.
Our present findings firstly reported the roles and mechanisms associated with miR-770 in glioma progression, highlighting miR-770 as a potential therapeutic target for glioma patients.
先前的研究表明，miR-770 的表达在许多肿瘤中失调。然而，miR-770 功能对神经胶质瘤的影响仍然是一个谜。本研究旨在探讨其在神经胶质瘤中的表达、细胞功能和临床特征。
我们分析了 RNA 测序数据，以探讨神经胶质瘤中异常表达的 miRNA。收集神经胶质瘤组织标本及其配对的正常组织，采用实时定量聚合酶链反应（qRT-PCR）分析检测 miR-770 的表达。统计分析 miR-770 与临床病理因素的相关性及其预后价值。然后，我们研究了一系列与癌症相关表型的改变，包括细胞活力、凋亡、集落形成和转移能力。Western blot 分析用于检测 EMT 相关蛋白和 PI3K/Akt 信号通路蛋白的表达变化。
我们鉴定出一种新型神经胶质瘤相关 miRNA miR-770，其在人神经胶质瘤组织中显著下调。RT-PCR 的结果进一步表明，miR-770 的表达在神经胶质瘤组织和细胞系中均显著下调。此外，miR-770 表达降低与较高的 WHO 分级、KPS 评分和较短的五年总生存期显著相关。然后，功能测定表明，miR-770 的过表达抑制了神经胶质瘤细胞的增殖、迁移、侵袭和 EMT 途径，并诱导其凋亡。此外，我们进一步表明，miR-770 的上调抑制了 PI3K-AKT 信号通路。
本研究首次报道了 miR-770 在神经胶质瘤进展中相关的作用和机制，强调了 miR-770 作为神经胶质瘤患者潜在治疗靶点的重要性。
