MicroRNA-1225-5p behaves as a tumor suppressor in human glioblastoma via targeting of IRS1

Abstract

Background: MicroRNAs (miRNAs) play an important role in cancer initiation, progression, and metastasis by directly regulating their target genes. Materials and methods: In this study, we observed that the miR-1225-5p expression level in glioblastoma tissues was significantly lower as compared with that in normal brain tissues, and its low expression was significantly associated with histopathological grade and poor patient prognosis. Results: Through establishing a miR-1225-5p overexpression glioblastoma cell line, we found that ectopic overexpression of miR-1225-5p inhibited the proliferation, migration, and invasion of glioblastoma cells in vitro. Moreover, the growth of a glioblastoma xenograft tumor was attenuated by overexpression of miR-1225-5p. Further integrative studies suggested that the insulin receptor substrate 1 (IRS1) was a direct functional target of miR-1225-5p in glioblastoma, and the mRNA and protein levels of IRS1 in six human glioblastoma cell lines (A172, SW1783, U87, LN-229, SW1088, and T98G) were significantly higher as compared with normal human astrocytes. Conclusion: These results suggest that miR-1225-5p may be a novel candidate for glioblastoma therapy.