Long Noncoding RNA WT1-AS Inhibit Cell Malignancy via miR-494-3p in Glioma

Abstract

Primary brain tumors are a rare occurrence in comparison to other malignancies, the most predominant form being glioma. Commonly, exposure to ionizing radiations and inheritance of associated conditions such a neurofibromatosis and tuberous sclerosis are the most common causes of development of glioma. However, understanding of the molecular mechanisms that drive glioma development is limited. We explore the role of aberration of microRNA namely <i>miR-494-3p</i> through long noncoding RNA <i>WT1-AS</i> in the development of gliomas. In this study, we found that, levels of <i>WT1-AS</i> were significantly reduced in glioma tissues and cell lines. The <i>miR-494-3p</i> levels were negatively correlated with <i>WT1-AS</i> levels. The cellular proliferation and invasiveness decreased in <i>WT1-AS</i> transfected cell lines. Further the half maximal inhibitory concentration (IC₅₀) of chemotherapeutic agent temozolomide was significantly reduced in the presence of <i>WT1-AS</i>. The cotransfection of <i>WT1-AS</i> and <i>miR-494-3p</i> reduced activation of phospho-AKT (p-AKT). Expression of <i>miR-494-3p</i> is modulated by binding to long noncoding RNA <i>WT1-AS</i>. Deregulation of WT1-AS leads to aberrant expression of <i>miR-494-3p</i> leading to hyperactivation of AKT. This malformation may result in altering protective immune responses in malignancies. Targeting of WT1-AS, miR-494-3p, and AKT may be novel therapeutic options in treatment of glioma.