Feng Tianda, Liu Yunhui, Li Chao, Li Zhen, Cai Heng
1 Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
2 Department of Neurosurgery, Guangxing Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Tumour Biol. 2017 Jul;39(7):1010428317716248. doi: 10.1177/1010428317716248.
Astrocytic tumors are the most common neuroepithelial neoplasms with high relapse rate after surgery. Understanding the molecular mechanisms for astrocytic tumorigenesis and progression will lead to early diagnosis and effective treatment of astrocytic tumors. The DEK mRNA and protein expression in normal brain tissues and astrocytic tumors was quantified. To investigate DEK functions in tumor cells, DEK gene was silenced with siRNA in U251 glioblastoma cells. Cell proliferation, cell cycle and apoptosis were then measured. The expression and activity of key genes that regulate cell proliferation and apoptosis were also measured. We identified DEK as a high expressed gene in astrocytic tumor tissues. DEK expression level was positively correlated with the pathological grade of astrocytic tumors. Gene silencing of DEK in U251 glioblastomas inhibited cell proliferation and blocked cells at G0/G1 phase of cell cycle. DEK depletion also induced cell apoptosis, with up-regulated expression of P53 and P21 and down-regulated expression of Bcl-2 and C-myc. The Caspase-3 activity in U251 cells was also significantly increased after knockdown. Our results provided evidences that DEK regulates proliferation and apoptosis of glioblastomas. DEK gene silencing may induce apoptosis through P53-dependent pathway. Our data indicated DEK plays multiple roles to facilitate tumor growth and maintenance. It can be used as a potential target for astrocytic tumor diagnosis and gene therapy.
星形细胞瘤是最常见的神经上皮肿瘤，术后复发率高。了解星形细胞瘤发生和进展的分子机制将有助于星形细胞瘤的早期诊断和有效治疗。对正常脑组织和星形细胞瘤中DEK mRNA和蛋白表达进行了定量分析。为了研究DEK在肿瘤细胞中的功能，在U251胶质母细胞瘤细胞中用小干扰RNA使DEK基因沉默。然后检测细胞增殖、细胞周期和凋亡情况。还检测了调节细胞增殖和凋亡的关键基因的表达和活性。我们发现DEK是星形细胞瘤组织中高表达的基因。DEK表达水平与星形细胞瘤的病理分级呈正相关。在U251胶质母细胞瘤中沉默DEK基因可抑制细胞增殖，并使细胞阻滞在细胞周期的G0/G1期。DEK缺失还诱导细胞凋亡，P53和P21表达上调，Bcl-2和C-myc表达下调。敲低后U251细胞中Caspase-3活性也显著增加。我们的结果表明DEK调节胶质母细胞瘤的增殖和凋亡。DEK基因沉默可能通过P53依赖途径诱导凋亡。我们的数据表明DEK在促进肿瘤生长和维持方面发挥多种作用。它可作为星形细胞瘤诊断和基因治疗的潜在靶点。
