MicroRNA-140 represses Glioma growth and metastasis by directly targeting ADAM9

Abstract

Glioma is the most frequent primary malignant tumor of the human brain. Recently, great progress has been made in the combined therapy of glioma. However, the clinical effects of these treatments and prognosis for patients with glioma remains poor. MicroRNAs (miRNAs) have been demonstrated to play important roles in the initiation and progression of various types of human cancers, also including glioma. The present study investigated the expression patterns of microRNA-140 (miR-140) in glioma, and the roles of MIR-140 in glioma cell proliferation, migration and invasion. The results showed that MIR-140 was significantly downreuglated in glioma tissues and cell lines, and low expression levels of MIR-140 were correlated with World Health Organization (WHO) grade and Karnofsky performance score (KPS) of glioma patients. Restoration of MIR-140 obviously suppressed glioma cell proliferation, migration and invasion. In addition, a disintegrin and metalloproteinase 9 (ADAM9) was identified as a novel direct target gene of MIR-140 in glioma. Furthermore, knockdown of ADAM9 simulated the tumor suppressor functions of MIR-140, while overexpression of ADAM9 abrogated these suppressive effects induced by MIR-140 in glioma cells. In conclusion, the present study demonstrated the expression and clinical roles of MIR-140 in glioma and suggested that MIR-140 inhibited proliferation, migration and invasion of glioma cells, partially at least via suppressing ADAM9 expression. Therefore, MIR-140 may be a novel candidate target for the development of therapeutic strategies for patients with glioma.