Qiu Guangting, Tong Wenjie, Jiang Chenghao, Xie Qingsong, Zou Jingfang, Luo Cong, Zhao Jianwei, Zhang Lu, Zhao Jiang
Department 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.
Department of Neurosurgery, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiao Tong University, Shanghai, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820919759. doi: 10.1177/1533033820919759.
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 through long noncoding RNA in the development of gliomas. In this study, we found that, levels of were significantly reduced in glioma tissues and cell lines. The levels were negatively correlated with levels. The cellular proliferation and invasiveness decreased in transfected cell lines. Further the half maximal inhibitory concentration (IC) of chemotherapeutic agent temozolomide was significantly reduced in the presence of . The cotransfection of and reduced activation of phospho-AKT (p-AKT). Expression of is modulated by binding to long noncoding RNA . Deregulation of WT1-AS leads to aberrant expression of 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.
与其他恶性肿瘤相比，原发性脑肿瘤较为罕见，最主要的形式是胶质瘤。通常，暴露于电离辐射以及相关疾病（如神经纤维瘤病和结节性硬化症）的遗传是胶质瘤发生的最常见原因。然而，对驱动胶质瘤发展的分子机制的了解有限。我们探讨了微小RNA（即通过长链非编码RNA）的异常在胶质瘤发展中的作用。在本研究中，我们发现，胶质瘤组织和细胞系中[具体物质]的水平显著降低。[具体物质]水平与[另一具体物质]水平呈负相关。在转染了[具体物质]的细胞系中，细胞增殖和侵袭性降低。此外，在存在[具体物质]的情况下，化疗药物替莫唑胺的半数最大抑制浓度（IC）显著降低。[具体物质]和[另一具体物质]的共转染降低了磷酸化AKT（p-AKT）的激活。[具体物质]的表达通过与长链非编码RNA[具体名称]结合来调节。WT1-AS的失调导致[具体物质]的异常表达，进而导致AKT的过度激活。这种畸形可能导致恶性肿瘤中保护性免疫反应的改变。靶向WT1-AS、miR-494-3p和AKT可能是治疗胶质瘤的新的治疗选择。
