microRNA-744 is downregulated in glioblastoma and inhibits the aggressive behaviors by directly targeting NOB1

In recent years, changes in microRNA (miRNA) expression have been detected in almost all human cancer types, including glioblastoma (GBM). Dysregulation of miRNAs may play tumor-suppressing or oncogenic roles in the initiation and progression of GBM, and may be involved in the regulation of multiple pathological behaviors. Therefore, identifying the clinical value and functional role of GBM-related miRNAs may provide effective therapeutic targets for the treatment of patients with this fatal malignancy. Dysregulation of miR-744 has been identified in several human cancer types. However, to the best of our knowledge, little is known concerning the expression pattern and biological roles of miR-744 in GBM. In this study, we found that miR-744 was significantly downregulated in GBM tissues and cell lines. Decreased miR-744 expression was significantly correlated with the Karnofsky Performance Scale (KPS) and World Health Organization (WHO) grade in GBM patients. miR-744 upregulation inhibited the proliferation, colony formation, migration, and invasion, in addition to inducing apoptosis of GBM cells in vitro. Inhibition of miR-744 had the opposite effect on these behaviors in GBM cells. Additionally, miR-744 attenuated the tumor growth of GBM cells in vivo. Furthermore, NIN1/RPN12 binding protein1 homolog (NOB1) was identified as a direct target gene of miR-744 in GBM cells. NOB1 was confirmed to be upregulated in GBM tissues, and this was inversely correlated with upregulation of miR-744 expression. Moreover, NOB1 knockdown exhibited similar inhibitory effects as miR-744 overexpression in GBM cells. Notably, recovered NOB1 expression counteracted the tumor-suppressing roles of miR-744 in the malignant phenotypes of GBM cells. Taken together, these results demonstrate that miR-744 directly targets NOB1 to inhibit the aggressive behaviors of GBM cells. Hence, the miR-744/NOB1 axis may be useful in the identification of novel therapies for GBM patients.