Yang Huan-Li, Gao Ya-Mei, Zhao Jin-An
Disinfection Supply Room, Weinan Central Hospital, Weinan, Shaanxi 714000, P.R. China.
Nursing Department, Weinan Central Hospital, Weinan, Shaanxi 714000, P.R. China.
Mol Med Rep. 2017 Sep;16(3):3634-3640. doi: 10.3892/mmr.2017.6951. Epub 2017 Jul 12.
miR‑140‑5p has been reported to be a tumor suppressor in several types of human cancer, however, little is known about its expression and function in human gliomas. The present study aimed to detect the expression of miR‑140‑5p in human glioma tissues and cell lines, and to investigate the effect of miR‑140‑5p on glioma cell growth, invasion and adhesion using in vitro gain‑of‑function and loss‑of‑function experiments. Furthermore, the hypothesis that Jagged1 (JAG1) may be a target gene of miR‑140‑5p was tested. Reverse transcription‑quantitative polymerase chain reaction analysis revealed that miR‑140‑5p was significantly downregulated in human glioma tissues and cell lines compared with normal tissues, and that its expression was correlated with the grade of gliomas. Transfection of a miR‑140‑5p mimic into SW1783 glioma cells promoted cell growth, invasion and adhesion, as determined by MTT, Transwell and cell adhesion assays respectively. By contrast, transfection of a miR‑140‑5p inhibitor had the opposite effect. A dual‑luciferase reporter assay confirmed that JAG1 was a target gene of miR‑140‑5p, and miR‑140‑5p inhibited JAG1 expression both at the mRNA and protein level. In addition, JAG1 overexpression reversed the effect of miR‑140‑5p on glioma cell growth, invasion and adhesion. In conclusion, the present study is the first to reveal that miR‑140‑5p acts as a tumor suppressor in human gliomas. JAG1 was demonstrated to be a novel target of miR‑140‑5p, and miR‑140‑5p exerted its inhibitory effect on human glioma growth and invasion, partly by suppressing JAG1. The present study may provide useful information toward novel targets for the treatment of gliomas.
据报道，miR-140-5p在几种人类癌症中是一种肿瘤抑制因子，然而，其在人类胶质瘤中的表达和功能却鲜为人知。本研究旨在检测miR-140-5p在人类胶质瘤组织和细胞系中的表达，并通过体外功能获得和功能丧失实验，研究miR-140-5p对胶质瘤细胞生长、侵袭和黏附的影响。此外，还验证了锯齿状蛋白1（JAG1）可能是miR-140-5p的靶基因这一假设。逆转录-定量聚合酶链反应分析显示，与正常组织相比，miR-140-5p在人类胶质瘤组织和细胞系中显著下调，且其表达与胶质瘤分级相关。分别通过MTT、Transwell和细胞黏附实验测定，将miR-140-5p模拟物转染到SW1783胶质瘤细胞中可促进细胞生长、侵袭和黏附。相比之下，转染miR-140-5p抑制剂则产生相反的效果。双荧光素酶报告基因实验证实JAG1是miR-140-5p的靶基因，且miR-140-5p在mRNA和蛋白质水平均抑制JAG1表达。此外，JAG1过表达可逆转miR-140-5p对胶质瘤细胞生长、侵袭和黏附的影响。总之，本研究首次揭示miR-140-5p在人类胶质瘤中作为肿瘤抑制因子发挥作用。JAG1被证明是miR-140-5p的一个新靶点，miR-140-5p对人类胶质瘤生长和侵袭的抑制作用部分是通过抑制JAG1实现的。本研究可能为胶质瘤治疗的新靶点提供有用信息。
