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抑癌基因 PTENP1 假基因表达降低促进了头颈鳞癌的恶性行为,并与患者的不良预后相关。

Decreased expression of pseudogene PTENP1 promotes malignant behaviours and is associated with the poor survival of patients with HNSCC.

机构信息

Department of Oral Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.

Shanghai Research Institute of Stomatology and Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.

出版信息

Sci Rep. 2017 Jan 23;7:41179. doi: 10.1038/srep41179.

Abstract

PTENP1, a pseudogene of PTEN, was previously reported to be a tumour suppressor in some cancer types. However, there was no evidence for the biological function and expression of PTENP1 in head and neck squamous cell carcinoma (HNSCC). Here, we evaluated the function and clinical implications of PTENP1 in HNSCC. Using RT-PCR and quantitative real-time PCR (qRT-PCR), we found that the level of PTENP1 was reduced in HNSCC specimens compared with adjacent tissues. A decrease in the PTENP1 copy number, but not in the PTEN copy number, was frequently observed in tumour cell lines (4 of 5 cell lines) by genomic real-time PCR. Decreased PTENP1 expression was significantly associated with a history of alcohol use (P = 0.034). Univariate and multivariate Cox regression analyses revealed that low expression of PTENP1 correlated with worse overall survival (OS, P = 0.005; HR:0.170; Cl:0.049 to 0.590) and disease-free survival (DFS, P = 0.009; HR:0.195; Cl:0.057 to 0.664) rates of HNSCC patients. Furthermore, ectopic PTENP1 expression inhibited the proliferation, colony formation and migration of HNSCC cells and the growth of xenograft HNSCC tumours. These results demonstrate that PTENP1 might play an important role in the initiation and progression of HNSCC.

摘要

PTENP1 是 PTEN 的假基因,先前有报道称其在某些癌症类型中是一种肿瘤抑制因子。然而,在头颈部鳞状细胞癌(HNSCC)中,没有关于 PTENP1 的生物学功能和表达的证据。在这里,我们评估了 PTENP1 在 HNSCC 中的功能和临床意义。通过 RT-PCR 和定量实时 PCR(qRT-PCR),我们发现与相邻组织相比,HNSCC 标本中 PTENP1 的水平降低。基因组实时 PCR 显示,在肿瘤细胞系中(5 个细胞系中的 4 个),PTENP1 拷贝数减少,但 PTEN 拷贝数没有减少。PTENP1 表达降低与饮酒史显著相关(P=0.034)。单因素和多因素 Cox 回归分析显示,PTENP1 低表达与 HNSCC 患者总生存(OS,P=0.005;HR:0.170;Cl:0.049 至 0.590)和无病生存(DFS,P=0.009;HR:0.195;Cl:0.057 至 0.664)的风险降低相关。此外,异位表达 PTENP1 抑制了 HNSCC 细胞的增殖、集落形成和迁移以及异种移植 HNSCC 肿瘤的生长。这些结果表明,PTENP1 可能在 HNSCC 的发生和发展中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c141/5255549/41865e6eb186/srep41179-f1.jpg

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