Over-expression of MiR-187 Inhibited Cell Proliferation and Metastasis of Glioma Via Down-regulating SMAD1

Objective: MicroRNAs (miRNAs) have been identified to participate in the tumorigenesis and progression of glioma. However, the expression and function of miR-187 have not been fully elucidated in glioma so far. Therefore, the aim of this study was to investigate the role of miR-187 in glioma and to explore the possible underlying mechanism.

Patients And Methods: The expression levels of miR-187 in 67 glioma tissues and 21 normal brain tissues, as well as 4 glioma-derived cell lines were measured using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). MiR-187 was overexpressed or inhibited in U251 or U87MG cells using miR-187 mimics or inhibitor transfection, respectively. Colony formation assay and Cell Counting Kit-8 (CCK-8) assay were employed to detect the proliferation ability of cells. Meanwhile, transwell assay and wound-healing assay were applied to evaluate the invasion and migration capacities of cells. Furthermore, Dual-Luciferase assay and Western blot analysis were used to verify the downstream target gene of miR-187 in glioma.

Results: MiR-187 expression was significantly lower in glioma tissues and cells when compared with normal brain tissues and cell lines. Up-regulation of miR-187 markedly reduced the proliferation, migration and invasion of U251 cells compared with the negative control group. However, down-regulation of miR-187 remarkably accelerated U87MG cell growth and metastasis compared with inhibitor negative control group. Furthermore, SMAD1 was identified as a direct target for miR-187 in glioma, which could be repressed by miR-187. In addition, over-expression of SMAD1 restored the influence of miR-187 mimics in glioma cells.

Conclusions: MiR-187 was lowly expressed in glioma tissues and cell lines. Acting as a tumor suppressor, miR-187 inhibited cell growth, invasion, and migration in glioma via repressing SMAD1 expression. Our findings might provide a novel insight into the biological diagnosis and treatment in glioma.