Huang Wei-Juan, Li Mei, Jin Xiao-Han, Huang Xiao-Jia, Zhao Wei, Tian Xiao-Peng
Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Department of Pharmacology, Jinan University, Guangzhou, China.
Oncotarget. 2017 Jun 21;8(40):67241-67253. doi: 10.18632/oncotarget.18589. eCollection 2017 Sep 15.
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 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 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 homozygous depletion and heterozygous deficiency, but both more infrequent gain and rare instances of amplification. The status of 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.
Pin2/TRF1相互作用端粒抑制剂1（PinX1）最初被鉴定为一种端粒酶抑制剂，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，PinX1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PinX1在几种人类癌症中的基因特征和生物学意义。我们的结果表明，缺失是最常见的改变类型，其缺失频率在癌肉瘤和腺癌的病理类型中经常出现。我们发现基因突变的情况很少，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内。此外，我们对cBioportal数据库中几种人类癌症的分析显示，纯合缺失和杂合缺陷更为常见，但获得和扩增的情况较少且罕见。基因改变的状态与预后相关，可能具有肿瘤类型特异性。因此，其在肿瘤发生和后期预后中的生物学功能较为复杂，可能涉及与NEIL2、R3HCC1、POLR3D、GTF2E2和INTS10的协同作用。此外，我们观察到PinX1与TERT、DKC1、PTGES3和HSP90AA1相互作用。在大多数选定的癌症组织中，PinX1 mRNA表达降低，这可能促进肿瘤生长并增强肿瘤发生能力。总的来说，我们的数据揭示了PinX1在各种人类癌症中的表达模式和潜在机制。需要进一步开展工作以全面研究其在肿瘤发生和进展中的作用。
