Genetic profile and biological implication of PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) in human cancers: an analysis using The Cancer Genome Atlas.
Genetic profile and biological implication of PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) in human cancers: an analysis using The Cancer Genome Atlas.
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PIN2/TRF1 相互作用端粒酶抑制剂 1 (PinX1) 在人类癌症中的遗传谱和生物学意义：使用癌症基因组图谱进行分析
DOI：
10.18632/oncotarget.18589
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Tian XP
中科院分区：
文献类型：
--
作者：
Huang WJ;Li M;Jin XH;Huang XJ;Zhao W;Tian XP
Pin 2/TRF 1-interacting telomere inhibitor 1（PinX 1）最初被鉴定为端粒酶抑制剂，参与维持端粒酶活性、端粒长度和染色体稳定性。然而，研究表明PinX 1在其他几种肿瘤类型中的表达模式可能具有相反的分子状态。因此，我们使用cBioportal数据库研究了PinX 1在几种人类癌症中的遗传特征和生物学意义。我们的研究结果表明PinX 1缺失占大多数的变化，其缺失频率在癌肉瘤和腺癌的病理类型中有规律地发生。我们发现PinX 1基因突变的例子很少，三维结构分析表明，这些突变位点总是位于端粒酶抑制剂结构域。此外，我们对cBioportal数据库中几种人类癌症的分析显示，PinX 1纯合缺失和PinX 1杂合缺陷更频繁，但PinX 1获得和PinX 1扩增的情况都更罕见。PinX 1基因改变的状态与预后相关，并且可能是肿瘤类型特异性的。因此，其在肿瘤发生和后期预后中的生物学功能是复杂的，并且可能涉及与NEIL 2、R3 HCC 1、P0 LR 3D、GTF 2 E2和INTS 10的协同工作。此外，我们观察到PinX 1与TERT、DKC 1、PTGES 3和HSP 90 AA 1相互作用。PinX 1 mRNA在大多数选定的癌组织中表达降低，这可以促进肿瘤生长并增强致瘤性。总的来说，我们的数据揭示了PinX 1在各种人类癌症中的表达模式和潜在机制。需要进一步的工作来全面研究其在肿瘤发生和发展中的作用。
Pin2/TRF1-interacting telomere inhibitor 1 (PinX1) was originally identified as a telomerase inhibitor, involved in maintaining telomerase activity, telomere length, and chromosomal stability. However, research has shown that PinX1 can have opposing molecular status in its expression patterns in several other tumor types. We thus investigated the genetic profile and biological implication of PinX1 in several human cancers using the cBioportal database. Our results showed that PinX1 deletion accounted for the most alterations, with the frequency of its deletion regularly occurring in pathological types of carcinosarcoma and adenocarcinoma. We found few instances of PinX1 gene mutations and 3D structural analysis demonstrated that these mutation sites were always located within telomerase inhibitor domains. Furthermore, our analysis of several human cancers from the cBioportal database revealed more frequent PinX1 homozygous depletion and PinX1 heterozygous deficiency, but both more infrequent PinX1 gain and rare instances of PinX1 amplification. The status of PinX1 genetic alterations was correlated with prognosis and may be tumor-type specific. As such, its biological function in tumorigenesis and later prognosis is complicated and may involve co-worked with NEIL2, R3HCC1, POLR3D, GTF2E2, and INTS10. In addition, we observed that PinX1 interacts with TERT, DKC1, PTGES3, and HSP90AA1. PinX1 mRNA expression was decreased in most selected cancer tissues, which could promote tumor growth and enhance tumorigenicity. Collectively, our data reveal PinX1 expression patterns and potential mechanisms in various human cancers. Further work will be needed to comprehensively examine its role in tumor genesis and progression.
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