FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma

Abstract

Glioblastoma is the most common primary malignancy of the adult central nervous system (CNS) and is associated with an exceptionally poor prognosis. Elucidation of the pathogenesis and molecular changes will help us to further understand the pathogenesis and progression of the disease and offer new therapeutic targets. FUS1 (TUSC2, tumor suppressor candidate 2) is a tumor-suppressor gene located on human chromosome 3p21. Restoration of FUS1 function in human non-small cell lung cancer (NSCLC) cells was found to significantly inhibit tumor cell growth and modulate the chemosensitivity of lung cancer cells. Yet, its role in human glioblastoma has rarely been addressed. In the present study, we demonstrated that low expression of FUS1 was detected in high-grade human glioma, implying that FUS1 expression is negatively associated with progression of the disease. Subsequent studies confirmed that FUS1 overexpression inhibited the proliferation, migration and invasion of human glioblastoma cells. In addition, we found that FUS1 overexpression significantly upregulated miR-197 expression in the glioblastoma cells. We also revealed that miR-197 suppressed the proliferation, migration and invasion of the cells as well as the silencing of miR-197 attenuated the biological functions of FUS1. Using human glioblastoma tissue samples, we demonstrated that miR-197 is negatively associated with metastasis. All the results demonstrated that FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma and implied that restoration of FUS1 and miR-197 could be new therapeutic strategies for glioblastoma.