Decreased expression of pseudogene PTENP1 promotes malignant behaviours and is associated with the poor survival of patients with HNSCC.
Decreased expression of pseudogene PTENP1 promotes malignant behaviours and is associated with the poor survival of patients with HNSCC.
复制标题
假基因 PTENP1 表达减少会促进恶性行为，并与 HNSCC 患者的不良生存率相关
DOI：
10.1038/srep41179
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发表时间：
2017-01-23
影响因子：
4.6
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Liu J;Xing Y;Xu L;Chen W;Cao W;Zhang C
PTENP1是PTEN的假基因，此前有报道称PTEN在某些癌症类型中具有肿瘤抑制作用。然而，PTENP1在头颈部鳞状细胞癌(HNSCC)中的生物学功能和表达尚无证据。在这里，我们评估PTENP1在HNSCC中的作用和临床意义。应用逆转录聚合酶链式反应和实时定量聚合酶链式反应，我们发现PTENP1在HNSCC组织中的表达水平较癌旁组织降低。基因组实时定量聚合酶链式反应发现，在肿瘤细胞系(4/5)中，PTENP1拷贝数减少，但PTEN拷贝数未见减少。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低表达与喉癌患者的总体生存率(OS，P = 0.005；HR：0.170；CI：0.049~0.590)和无瘤生存率(DFS，P = 0.009；HR：0.195；CI：0.057~0.664)相关。此外，异位表达PTENP1抑制HNSCC细胞的增殖、集落形成和迁移，并抑制HNSCC移植瘤的生长。这些结果表明，PTENP1可能在HNSCC的发生发展中起重要作用。
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.