Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells
Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells
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DOI：
10.1007/s11060-017-2457-1
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发表时间：
2017-06-01
影响因子：
3.9
通讯作者：
Toda, Masahiro
中科院分区：
文献类型：
--
作者：
Kikuchi, Ryogo;Sampetrean, Oltea;Toda, Masahiro
DEP domain containing 1（DEPDC 1）是一种在癌细胞中表达的新型癌抗原，具有致瘤活性和高免疫原性。虽然DEPDC 1已被预测为用于癌症疫苗的开发的有用抗原，但其在胶质瘤中的病理生理作用尚未被研究。本研究分析DEPDC 1在恶性胶质瘤中的表达及功能。通过Western印迹和定量聚合酶链反应（PCR）评估神经胶质瘤细胞系、神经胶质瘤组织和脑肿瘤起始细胞（BTIC）中DEPDC 1的表达。研究了DEPDC 1下调对胶质瘤细胞生长和核因子κ B（NF κ B）信号转导的影响。使用人神经胶质瘤细胞和诱导的小鼠脑肿瘤干细胞（imBTSC）在小鼠神经胶质瘤模型中评估总存活率，以确定体内DEPDC 1抑制的效果。DEPDC 1在胶质瘤细胞系、组织和BTIC中表达增加。通过小干扰RNA（siRNA）抑制内源性DEPDC 1表达可抑制胶质瘤细胞活力并通过NF κ B信号转导诱导凋亡。在使用人胶质瘤细胞和imBTSC的小鼠胶质瘤模型中，DEPDC 1表达的下调延长了总生存期。这些结果表明，DEPDC 1代表用于治疗胶质瘤的靶分子。
DEP domain containing 1 (DEPDC1) is a novel oncoantigen expressed in cancer cells, which presents oncogenic activity and high immunogenicity. Although DEPDC1 has been predicted to be a useful antigen for the development of a cancer vaccine, its pathophysiological roles in glioma have not been investigated. Here, we analyzed the expression and function of DEPDC1 in malignant glioma. DEPDC1 expression in glioma cell lines, glioma tissues, and brain tumor initiating cells (BTICs) was assessed by western blot and quantitative polymerase chain reaction (PCR). The effect of DEPDC1 downregulation on cell growth and nuclear factor kappa B (NF kappa B) signaling in glioma cells was investigated. Overall survival was assessed in mouse glioma models using human glioma cells and induced mouse brain tumor stem cells (imBTSCs) to determine the effect of DEPDC1 suppression in vivo. DEPDC1 expression was increased in glioma cell lines, tissues, and BTICs. Suppression of endogenous DEPDC1 expression by small interfering RNA (siRNA) inhibited glioma cell viability and induced apoptosis through NF kappa B signaling. In mouse glioma models using human glioma cells and imBTSCs, downregulation of DEPDC1 expression prolonged overall survival. These results suggest that DEPDC1 represents a target molecule for the treatment of glioma.