miR-4530 inhibits the malignant biological behaviors of human glioma cells by directly targeting RTEL1
miR-4530 inhibits the malignant biological behaviors of human glioma cells by directly targeting RTEL1
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miR-4530直接靶向RTEL1抑制人胶质瘤细胞的恶性生物学行为
DOI：
10.1093/abbs/gmaa126
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发表时间：
2020
影响因子：
3.7
通讯作者：
Ke Gao
中科院分区：
文献类型：
--
作者：
Tuo Wang;Yan Zhang;Bo Cui;Maode Wang;Ya Li;Ke Gao
脑胶质瘤是最常见的原发性脑肿瘤，具有较高的发病率和死亡率。microRNA（miRNAs）的异常表达参与胶质瘤的进展。本研究旨在阐明miR-4530在胶质瘤发病机制中的作用。检测miR-4530在人脑胶质瘤临床组织和细胞系（包括U251和T98 G）中的表达。利用在线工具预测miR-4530的靶基因RTEL 1，并通过荧光素酶报告基因分析进行验证。慢病毒感染、质粒转染和miRNA模拟物用于操纵基因表达。使用CCK-8方法测定细胞增殖，并使用transwell实验测定迁移和侵袭测定。结晶紫染色法检测细胞集落形成，膜联蛋白V/PI染色法检测细胞凋亡。在使用U251细胞异种移植的裸鼠中评估miR-4530的抗肿瘤作用。我们的研究结果显示miR-4530在人脑胶质瘤组织和细胞系中显著下调。miR-4530过表达可抑制U251和T98 G细胞的恶性行为，包括增殖减少，集落形成、迁移和侵袭减少，凋亡增加。进一步的机制研究表明，RTEL 1是miR-4530在胶质瘤中的直接功能靶点，其过表达显著逆转了miR-4530模拟物抑制这些恶性行为的作用。此外，miR-4530过表达抑制裸鼠移植瘤U251胶质瘤的生长。因此，miR-4530作为一种抑癌基因，能够抑制人脑胶质瘤细胞的恶性生物学行为，其机制与直接靶向RTEL 1有关。miR-4530/RTEL 1轴是胶质瘤的潜在治疗靶点。
Human glioma is the most common primary brain tumor and is associated with high morbidity and mortality. Aberrant expressions of microRNAs (miRNAs) are involved in glioma progression. In the present study, we aimed to elucidate the roles of miR-4530 in the pathogenesis of gliomas. miR-4530 expression was examined in human glioma clinical tissues and cell lines including U251 and T98G. The target gene of miR-4530,RTEL1, was predicted with online tools and validated by luciferase reporter assay. Lentivirus infection, transfection of plasmids, and miRNA mimics were used to manipulate gene expression. Cell proliferation was determined using the CCK-8 method, and migration and invasion assays were determined with transwell experiments. Colony formation was measured by crystal violet staining, while apoptosis was determined by Annexin V/PI staining. The anti-tumor effects of miR-4530 were evaluated in nude mice xenografted using U251 cells. Our results showed that miR-4530 was significantly down-regulated in human glioma tissues and cell lines. miR-4530 over-expression inhibited the malignant behaviors of U251 and T98G cells, including reduced proliferation, diminished colony formation, migration and invasion, and increased apoptosis. Further mechanistic investigations revealed thatRTEL1is a direct functional target of miR-4530 in gliomas, and its over-expression remarkably reverses the effects of miR-4530 mimics on inhibiting these malignant behaviors. In addition, miR-4530 over-expression inhibited the growth of xenografted U251 glioma in nude mice. Therefore,miR-4530acts as a tumor-suppressor gene and inhibits the malignant biological behaviors of human glioma cells, which is associated with directly targetingRTEL1. The miR-4530/RTEL1 axis is a potential therapeutic target for gliomas.