PDF(Pubmed)
Abstract：
Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1β to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus.
摘要：
人乳头瘤病毒16（HPV16）感染与几种类型的癌症有关，例如头部和颈部，子宫颈,肛门,还有阴茎癌.其致癌潜力是由于E6和E7癌蛋白促进与细胞转化相关的改变的能力。HPV16E6和E7癌蛋白增加代谢重编程，癌症的标志之一，通过增加缺氧诱导因子1α（HIF-1α）的稳定性，从而增加其靶基因的表达水平。在这份报告中,通过生物信息学分析，我们通过E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α轴显示了HPV16癌蛋白E6和E7对癌症代谢重编程的可能影响。我们建议E6和E7与VHL相互作用，CUL2和ELOC形成E3泛素连接酶复合物，该复合物泛素化HIF-1α以通过蛋白酶体降解。根据数据库中的信息,建议E6通过阻断其与HIF-1α的相互作用与VHL相互作用。另一方面,E7与CUL2和ELOC相互作用，防止它们分别与VHL和RBX1结合。因此,HIF-1α稳定并与HIF-1β结合，形成与缺氧反应元件（HREs）结合的活性HIF1复合物，允许与能量代谢相关的基因表达。此外,我们建议E6和E7在PHD2，VHL，CUL2和ELOC基因表达。这里,我们提出了一些针对PHD2，VHL，CUL2和ELOCmRNA。E6和E7的作用可能是HIF-1α的非羟基化和非泛素化，在稳定时可以调节癌症中代谢重编程所涉及的代谢过程，不降解，和转位到细胞核。
