Department of Neurosurgery, Cancer Hospital, Harbin Medical University, Harbin, China.
Department of Ultrasound, Cancer Hospital, Harbin Medical University, Harbin, China.
Neoplasma. 2019 May 23;66(3):350-356. doi: 10.4149/neo_2018_180714N484. Epub 2019 Feb 14.
The aberrant expression of microRNA-375 (miR-375) has been proved to be associated with carcinogenesis. However, the role of miR-375 in glioblastoma (GBM) remains unknown. The aim of this study was to investigate biological functions and its molecular mechanisms of miR-375 in GBM cells. In this study, real-time PCR results showed that the level of miR-375 expression in GBM tissues and GBM cell lines (U87 and U251) was decreased. Using MTT assay, Transwell migration and invasion assay, we demonstrated that miR-375 overexpression significantly suppress cell proliferation, cell migration and cell invasion capacity in U87 and U251 cells. However, downregulation of miR-375 had reverse effects on cell proliferation, migration and invasion. Targeting association analysis, dual luciferase assay, RT-PCR and western blot analysis results confirmed that miR-375 could target the 3'UTR of Wnt5a mRNA and regulated its protein expression. Further studies also find overexpression of Wnt5a could significantly reverse miR-375-mediated proliferation, migration and invasion on U87 and U251 cells. Therefore, we concluded that miR-375 inhibited the proliferation and invasion of GBM by regulating Wnt5a and might be a possible therapeutic agent for GBM.
miR-375 的异常表达已被证明与癌症发生有关。然而，miR-375 在胶质母细胞瘤（GBM）中的作用尚不清楚。本研究旨在探讨 miR-375 在 GBM 细胞中的生物学功能及其分子机制。
在这项研究中，实时 PCR 结果表明，miR-375 在 GBM 组织和 GBM 细胞系（U87 和 U251）中的表达水平降低。通过 MTT 测定、Transwell 迁移和侵袭实验，我们证明 miR-375 过表达可显著抑制 U87 和 U251 细胞的增殖、迁移和侵袭能力。然而，miR-375 的下调则对细胞增殖、迁移和侵袭具有相反的作用。
靶基因关联分析、双荧光素酶报告基因实验、RT-PCR 和 Western blot 分析结果证实，miR-375 可靶向 Wnt5a mRNA 的 3'UTR 并调节其蛋白表达。进一步的研究还发现，Wnt5a 的过表达可显著逆转 miR-375 介导的 U87 和 U251 细胞增殖、迁移和侵袭。
因此，我们得出结论，miR-375 通过调节 Wnt5a 抑制 GBM 的增殖和侵袭，可能成为 GBM 的一种潜在治疗药物。
