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Long Noncoding RNA WT1-AS Inhibit Cell Malignancy via miR-494-3p in Glioma
Guangting Qiu1, Wenjie Tong2, Chenghao Jiang1
1Department of Neurosurgery, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
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 miR-494-3p through long noncoding RNA WT1-AS in the development of gliomas. In this study, we found that, levels of WT1-AS were significantly reduced in glioma tissues and cell lines. The miR-494-3p levels were negatively correlated with WT1-AS levels. The cellular proliferation and invasiveness decreased in WT1-AS transfected cell lines. Further the half maximal inhibitory concentration (IC50) of chemotherapeutic agent temozolomide was significantly reduced in the presence of WT1-AS. The cotransfection of WT1-AS and miR-494-3p reduced activation of phospho-AKT (p-AKT). Expression of miR-494-3p is modulated by binding to long noncoding RNA WT1-AS. Deregulation of WT1-AS leads to aberrant expression of miR-494-3p 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.
Insights
Long noncoding RNA WT1-AS and microRNA miR-494-3p play key roles in glioma development. Targeting these molecules and AKT may offer new therapeutic strategies for glioma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gliomas are the most common primary brain tumors, but their molecular drivers are not fully understood.
- MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- Aberrant gene expression is a hallmark of glioma, necessitating research into novel molecular pathways.
Purpose of the Study:
- To investigate the role of the lncRNA WT1-AS and its interaction with miR-494-3p in glioma pathogenesis.
- To explore the potential of targeting WT1-AS, miR-494-3p, and AKT as therapeutic strategies for glioma.
Main Methods:
- Quantitative analysis of WT1-AS and miR-494-3p expression in glioma tissues and cell lines.
- In vitro studies involving transfection of WT1-AS and miR-494-3p in glioma cells.
- Assessment of cellular proliferation, invasiveness, and response to temozolomide.
- Western blot analysis to evaluate AKT phosphorylation levels.
Main Results:
- WT1-AS expression was significantly reduced in glioma tissues and cell lines.
- miR-494-3p levels were inversely correlated with WT1-AS levels.
- WT1-AS transfection reduced glioma cell proliferation and invasiveness and enhanced temozolomide sensitivity.
- Cotransfection of WT1-AS and miR-494-3p decreased phospho-AKT (p-AKT) activation.
Conclusions:
- WT1-AS regulates miR-494-3p expression, and their deregulation contributes to glioma development via AKT hyperactivation.
- Targeting the WT1-AS/miR-494-3p/AKT axis presents a promising therapeutic avenue for glioma treatment.
- Further research into this pathway could uncover novel strategies to improve glioma patient outcomes.
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