Ma Yunlong, Zhu Bin, Liu Xiaoguang, Liu Zhongjun, Jiang Liang, Wei Feng, Yu Miao, Wu Fengliang, Zhou Hua, Xu Nanfang, Liu Xiao, Yong Lei, Wang Yongqiang, Wang Peng, Liang Chen, He Guanping
Department of Orthopedics, Peking University Third Hospital, Beijing 100191, China.
The Center for Pain Medicine, Peking University Third Hospital, Beijing 100191, China.
Oncotarget. 2017 Aug 11;8(40):68365-68380. doi: 10.18632/oncotarget.20190. eCollection 2017 Sep 15.
The oncogenetic function of inhibitory member of the apoptosis stimulating protein of p53 family (iASPP) in chordoma is unclear and remains to elucidate. The expression of iASPP in chordoma tissues and cells, its correlation to clinicopathological parameters and the effect on the patients' prognosis were evaluated. Cellular proliferation, invasion and cisplatin-response were observed after the iASPP knockdown or overexpression . Co-Immunoprecipitation assay was used to explore the interaction between iASPP and p53. The regulation of miRNA-124 on the expression and apoptotic function of iASPP was explored after transiently transfecting cells with miRNA-124 mimics or inhibitor. Results indicated that iASPP overexpressed in chordoma tissues and cells. Its overexpression was associated with tumor invasion and local recurrence, and was predictive of patients' poor prognosis. Cells with iASPP-silence showed a decreased ability of proliferation and invasion, but an increasing sensitivity to cisplatin. Besides, iASPP could combine with p53 in either endogenous or exogenous detection. Post-transcriptionally, miRNA-124 negatively regulated the expression of iASPP, which further led to the changes of apoptosis-related proteins. Thus, iASPP overexpression is associated with the clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and the sensitivity to cisplatin.
p53家族凋亡刺激蛋白抑制成员(iASPP)在脊索瘤中的致癌功能尚不清楚,有待阐明。本研究评估了iASPP在脊索瘤组织和细胞中的表达、其与临床病理参数的相关性以及对患者预后的影响。在iASPP基因敲低或过表达后,观察细胞增殖、侵袭和顺铂反应情况。采用免疫共沉淀试验探讨iASPP与p53之间的相互作用。在用miRNA-124模拟物或抑制剂瞬时转染细胞后,研究miRNA-124对iASPP表达和凋亡功能的调控作用。结果表明,iASPP在脊索瘤组织和细胞中过表达。其过表达与肿瘤侵袭和局部复发相关,可预测患者预后不良。iASPP沉默的细胞增殖和侵袭能力降低,但对顺铂的敏感性增加。此外,在内源性或外源性检测中,iASPP均可与p53结合。转录后,miRNA-124负向调控iASPP的表达,进而导致凋亡相关蛋白的变化。因此,iASPP过表达与脊柱脊索瘤的临床结局相关,并影响细胞增殖、侵袭以及对顺铂的敏感性。