Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.
Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.
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蛋白酶体激活剂 PA28 α 的过度表达可作为口腔鳞状细胞癌的预后因素
DOI：
10.1186/s13046-016-0309-z
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发表时间：
2016-02-19
期刊：
影响因子：
--
通讯作者：
Chen Q
中科院分区：
文献类型：
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作者：
Feng X;Jiang Y;Xie L;Jiang L;Li J;Sun C;Xu H;Wang R;Zhou M;Zhou Y;Dan H;Wang Z;Ji N;Deng P;Liao G;Geng N;Wang Y;Zhang D;Lin Y;Ye L;Liang X;Li L;Luo G;Feng M;Fang J;Zeng X;Wang Z;Chen Q
尽管口腔鳞状细胞癌(OSCC)的诊断和治疗最近取得了进展，但疾病复发仍然很常见，并且与死亡率密切相关。因此，为治疗和诊断目的确定新的靶点至关重要。我们的目的是研究蛋白酶体激活剂PA28α在口腔鳞癌中的作用。结合肿瘤分析，检测口腔鳞癌细胞系和组织中PA28α的表达。在一个大型口腔鳞癌患者队列中，对PA28α表达的预后价值进行了评估。主要临床终点是无复发和总存活率。在体外和体内模型中，研究了PA28siRNA在口腔鳞癌中的功能参与。PA28α在口腔鳞癌细胞系和肿瘤组织中高表达。PA28α高表达与肿瘤复发和总生存期显著相关。特异性下调PA2 8α在体外可抑制口腔鳞癌细胞的增殖、迁移和侵袭，并可抑制口腔鳞癌移植瘤的生长。多因素COX回归分析显示，PA28α是独立的预后预测因素。这些结果提示，PA28α参与口腔鳞癌的发生，并可能作为一个潜在的预后因素。本文的在线版本(doi：10.1186/s13046-0160309-z)包含补充材料，授权用户可以使用。
Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC. The expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown. PA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors. These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor. The online version of this article (doi:10.1186/s13046-016-0309-z) contains supplementary material, which is available to authorized users.