Cancer Management and Research (Dec 2019)
Decreased expression of miR-410-3p correlates with poor prognosis and tumorigenesis in human glioma
Abstract
Chaojia Wang,1 Shulan Huang,2 Shanshan Rao,1 Juntao Hu,1 Yuqiang Zhang,1 Jie Luo,1 Hui Wang1 1Department of Neurology, Taihe Affiliated Hospital, Hubei University of Medicine, Shiyan 442000, People’s Republic of China; 2Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of ChinaCorrespondence: Hui WangDepartment of Neurology, Taihe Hospital Affiliated to Hubei University of Medicine, No. 32 South Renmin Road, Shiyan 442000, People’s Republic of ChinaTel +86 719 880 1712Email [email protected]: Gliomas are the most common type of primary tumors in the central nervous system. This study aimed to investigate the biological role of miR-410-3p in glioma and elucidate the potential molecular mechanisms involved.Methods: The expression levels of miR-410-3p in clinical tissue samples and glioma cell lines were determined using qRT-PCR analysis. The clinical significance of miR-410-3p in glioma was evaluated using Kaplan-Meier survival analysis and Fisher’s exact test. The effects of miR-410-3p on glioma cell proliferation, apoptosis, migration and invasion were investigated using MTT assays, flow cytometry, transwell migration and invasion assays. Besides, corresponding mechanistic studies were carried out.Results: miR-410-3p was significantly down-regulated in glioma tissues. Besides, Kaplan-Meier analysis demonstrated that patients with low miR-410-3p expression had a shorter overall survival. Decreased miR-410-3p expression was associated with larger tumor size, lower Karnofsky performance score (KPS), and higher World Health Organization (WHO) grade. Over-expression of miR-410-3p suppressed cell proliferation, migration, and invasion, and accelerated apoptosis; whereas depletion of miR-410-3p facilitated cell proliferation, migration, and invasion, and inhibited apoptosis. Mechanistic investigations demonstrated that Ras-related protein 1A (RAP1A) was a direct target of miR-410-3p, and that rescue of RAP1A expression reversed miR-410-3p over-expression-induced inhibitory effects on cell proliferation, migration, and invasion. Notably, miR-410-3p over-expression repressed tumor growth in mouse xenograft models.Conclusion: Our findings indicate that miR-410-3p functions as a tumor suppressor in glioma by directly targeting RAP1A. Thus, this study may provide some new insights into gliomagenesis and progression.Keywords: miR-410-3p, RAP1A, poor prognosis, tumorigenesis, glioma
