Shen Hao, Xu Ling, You Chunyue, Tang Huaibo, Wu Haitao, Zhang Yong, Xie Mingxiang
Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.
Oncol Lett. 2021 Feb;21(2):156. doi: 10.3892/ol.2020.12417. Epub 2020 Dec 31.
Glioma is the most common brain tumor in adults. microRNAs (miRNAs/miRs) play an essential role in tumor development and progression. The present study aimed to investigate the potential clinical significance and function of miR-665 in glioma. Reverse transcription-quantitative PCR analysis was used to detect the expression of miR-665 in glioma tissues and cells. Survival curves were constructed using the Kaplan-Meier method. Cox regression analysis was performed to investigate the prognostic significance of miR-665. Cell Counting Kit-8 and Transwell assays were used to evaluate the role of miR-665 in glioma. Bioinformatics analysis and Dual-luciferase reporter assays were used to predict the putative direct targets of miR-665. Western blotting was used to evaluate the activity of the Wnt/β-catenin pathway. The relative expression of miR-665 was decreased in glioma tissues and cells and this downregulation was significantly associated with the Karnofsky performance scale score and World Health Organisation grade. Patients with glioma with low miR-665 expression had a shorter overall survival time compared with the high expression group. Besides, overexpression of miR-665 suppressed the proliferation, migration and invasion of glioma cells, while knockdown of miR-665 promoted these cellular behaviors. High mobility group box (HMGB)1 was a direct target of miR-665. It was also demonstrated that miR-665 may suppress glioma progression by targeting HMGB1 and inhibiting the Wnt/β-catenin pathway. Taken together, these data suggested that miR-665 may have a tumor suppressor role in glioma by targeting HMGB1. Therefore, miR-665 may be a novel prognostic biomarker and the miR-665/HMGB1 axis may be a novel therapeutic target for the treatment of glioma.
胶质瘤是成人中最常见的脑肿瘤。微小RNA（miRNA/miR）在肿瘤发生和发展中起重要作用。本研究旨在探讨miR-665在胶质瘤中的潜在临床意义和功能。采用逆转录定量PCR分析检测胶质瘤组织和细胞中miR-665的表达。使用Kaplan-Meier方法构建生存曲线。进行Cox回归分析以研究miR-665的预后意义。使用细胞计数试剂盒-8和Transwell实验评估miR-665在胶质瘤中的作用。采用生物信息学分析和双荧光素酶报告基因实验预测miR-665的假定直接靶点。使用蛋白质免疫印迹法评估Wnt/β-连环蛋白信号通路的活性。miR-665在胶质瘤组织和细胞中的相对表达降低，这种下调与卡氏功能状态评分和世界卫生组织分级显著相关。与高表达组相比，miR-665表达低的胶质瘤患者总生存时间较短。此外，miR-665的过表达抑制了胶质瘤细胞的增殖、迁移和侵袭，而敲低miR-665则促进了这些细胞行为。高迁移率族蛋白B1（HMGB1）是miR-665的直接靶点。还证明miR-665可能通过靶向HMGB1并抑制Wnt/β-连环蛋白信号通路来抑制胶质瘤进展。综上所述，这些数据表明miR-665可能通过靶向HMGB1在胶质瘤中发挥肿瘤抑制作用。因此，miR-665可能是一种新型的预后生物标志物，miR-665/HMGB1轴可能是治疗胶质瘤的新型治疗靶点。
