Jian Yan, Xu Chun-Hua, Li You-Ping, Tang Bin, Xie She-Hao, Zeng Er-Ming
Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R China.
Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R China
Biosci Rep. 2019 Aug 13;39(8). doi: 10.1042/BSR20182226. Print 2019 Aug 30.
microRNAs (miRNAs) have been found to affect various cancers, and expression of numerous miRNAs is revealed in glioma. However, the role of microRNA-30b-3p (miR-30b-3p) in glioma remains elusive. Therefore, the present study aims to explore the specific mechanism by which miR-30b-3p influence the development of glioma in relation to the AKT signaling pathway. First, glioma cell lines were collected with miR-30b-3p and reversion-inducing cysteine-rich protein with kazal motifs (RECK) expression measured. The functional role of miR-30b-3p and RECK in glioma was determined via gain- and loss-of-function approaches. Subsequently, the expression of invasion- and migration-related factors (MMP-2 and MMP-9) and the AKT signaling pathway-related factors (AKT, p-AKT and PI3K-p85) was detected. Moreover, experiments were also conducted to investigate how miR-30b-3p influences tumorigenesis. The results showed that miR-30b-3p was up-regulated and RECK was down-regulated in glioma. RECK was a target gene of miR-30b-3p. Decreased miR-30b-3p and overexpressed RECK led to decreased expression of MMP-2, MMP-9 and p-AKT. Overexpressed RECK and LY294002 could decrease p-AKT and PI3K-p85 expression accompanied with unchanged expression of total protein of AKT. Additionally, proliferation, migration and invasion of glioma cells and tumor formation in nude mice were repressed owing to reduced expression of miR-30b-3p or elevated expression of RECK. In summary, miR-30b-3p inhibition suppresses metastasis of glioma cells by inactivating the AKT signaling pathway via RECK up-regulation, providing a new target for glioma treatment.
微小RNA(miRNA)已被发现会影响多种癌症,并且在胶质瘤中发现了众多miRNA的表达。然而,微小RNA - 30b - 3p(miR - 30b - 3p)在胶质瘤中的作用仍不清楚。因此,本研究旨在探讨miR - 30b - 3p影响胶质瘤发展与AKT信号通路相关的具体机制。首先,收集胶质瘤细胞系并检测miR - 30b - 3p和含kazal基序的逆转诱导富含半胱氨酸蛋白(RECK)的表达。通过功能获得和功能缺失方法确定miR - 30b - 3p和RECK在胶质瘤中的功能作用。随后,检测侵袭和迁移相关因子(基质金属蛋白酶 - 2和基质金属蛋白酶 - 9)以及AKT信号通路相关因子(AKT、磷酸化AKT和磷脂酰肌醇 - 3激酶p85)的表达。此外,还进行了实验以研究miR - 30b - 3p如何影响肿瘤发生。结果表明,miR - 30b - 3p在胶质瘤中上调而RECK下调。RECK是miR - 30b - 3p的靶基因。miR - 30b - 3p降低和RECK过表达导致基质金属蛋白酶 - 2、基质金属蛋白酶 - 9和磷酸化AKT表达降低。RECK过表达和LY294002可降低磷酸化AKT和磷脂酰肌醇 - 3激酶p-85表达,而AKT总蛋白表达不变。此外,由于miR - 30b - 3p表达降低或RECK表达升高,胶质瘤细胞的增殖、迁移和侵袭以及裸鼠体内肿瘤形成受到抑制。总之,抑制miR - 30b - 3p通过上调RECK使AKT信号通路失活,从而抑制胶质瘤细胞转移,为胶质瘤治疗提供了新靶点。