Glioma is the most common highly malignant primary brain tumor. MicroRNA-519d-3p exerts important effects in several tumors, but its functional role in glioma remained poorly understood. In this study, we found miR-519d-3p expression was significantly decreased in glioma tissues and cell lines. Moreover, the in vitro experiments showed that overexpression of miR-519d-3p suppressed cell proliferation and induced cell cycle G0/G1 phase arrest using MTT and flow cytometry assays in glioma cell lines, U87 and U251. Mechanistically, Cyclin D1 (CCND1) was predicted and confirmed as the direct target genes of miR-519d-3p using luciferase report assay. In addition, knockdown of CCND1 imitated the suppressive effects of miR-519d-3p on cell proliferation and cell cycle progression. Furthermore, restoration of CCND1 reversed the effects of miR-519d-3p overexpression in glioma cells. Taken together, these data demonstrate that suppression of CCND1 by miR-519d-3p might be a therapeutic target for glioma.Abbreviations miR-519d-3p: microRNA-519d-3p; CCND1: Cyclin D1; ATCC: American Type Culture Collection; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PI: propidium iodide; WT: wild type; MUT: mutant type; SD: standard deviation.

中文翻译：

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MicroRNA-519d-3p通过靶向CCND1抑制神经胶质瘤中的细胞增殖和细胞周期G1 / S过渡。

胶质瘤是最常见的高度恶性原发性脑肿瘤。MicroRNA-519d-3p在几种肿瘤中发挥重要作用，但其在神经胶质瘤中的功能作用仍知之甚少。在这项研究中，我们发现神经胶质瘤组织和细胞系中miR-519d-3p表达显着降低。此外，体外实验表明，在胶质瘤细胞系U87和U251中使用MTT和流式细胞仪检测，miR-519d-3p的过表达抑制细胞增殖并诱导细胞周期G0 / G1期阻滞。从机理上讲，使用荧光素酶报告测定法预测并确认了Cyclin D1（CCND1）是miR-519d-3p的直接靶基因。另外，敲低CCND1模仿了miR-519d-3p对细胞增殖和细胞周期进程的抑制作用。此外，CCND1的恢复逆转了神经胶质瘤细胞中miR-519d-3p过表达的作用。综上所述，这些数据表明miR-519d-3p对CCND1的抑制可能是神经胶质瘤的治疗靶标。CCND1：Cyclin D1；ATCC：美国典型文化收藏；MTT：3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑；PI：碘化丙啶；WT：野生型；MUT：突变型；SD：标准偏差。