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Abstract：
The pituitary tumor-transforming gene 1 (PTTG1) is an oncogene involved in chromosomal segregation, DNA repair, apoptosis, and metabolism. PTTG1 can be used for clinical diagnosis and treatment and is a potential target for oropharyngeal carcinoma. The proliferation and viability of Cal27 and FaDu cells were assessed using the CCK-8 assay. Real-time PCR and western blotting, respectively, were used to analyze the mRNA and protein expression levels of PTTG1 and IFIH1. The interaction between PTTG1 mRNA and the translational regulatory protein IFIH1 was analyzed using RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. PTTG1 protein was significantly overexpressed in oropharyngeal carcinoma, whereas PTTG1 mRNA was not. We hypothesized that a translation regulatory protein plays a post-transcriptional role in PTTG1. The IFIH1 protein specifically bound to the 42-52 nt region of PTTG1 mRNA, promoted the translation of PTTG1, and promoted the proliferation of oropharyngeal cancer cells. Administration of the PTTG1 inhibitor PHA-848125 and silencing of IFIH1 synergistically decreased the expression of PTTG1, inhibited the proliferation of oropharyngeal cancer cells, and indicated a good prognosis. We found that the IFIH1-PTTG1 axis could regulate the PHA-848125 response and functionally mediate inter-individual oropharyngeal cancer susceptibility and prognosis. This study aimed to confirm the upstream regulatory genes of PTTG1 and further investigate the specific interactions in this signaling pathway, which will provide a new approach for the treatment of oropharyngeal carcinoma.
摘要：
垂体肿瘤转化基因1(PTTG1)是一个参与染色体分离的癌基因,DNA修复,凋亡，和新陈代谢。PTTG1可用于临床诊断和治疗，是口咽恶性肿瘤的潜在靶点。使用CCK-8测定评估Cal27和FaDu细胞的增殖和活力。实时PCR和蛋白质印迹,分别,分别分析PTTG1和IFIH1的mRNA和蛋白表达水平。使用RNA下拉法分析PTTG1mRNA与翻译调节蛋白IFIH1之间的相互作用，RNA免疫沉淀，和荧光素酶报告基因测定。PTTG1蛋白在口咽癌中显著过表达,而PTTG1mRNA没有。我们假设翻译调节蛋白在PTTG1中起转录后作用。IFIH1蛋白与PTTG1mRNA的42-52nt区域特异性结合，促进PTTG1的翻译，促进口咽癌细胞的增殖。给予PTTG1抑制剂PHA-848125和沉默IFIH1协同降低PTTG1的表达，抑制口咽癌细胞的增殖，预后良好。我们发现IFIH1-PTTG1轴可以调节PHA-848125反应，并在功能上介导个体间口咽癌的易感性和预后。本研究旨在确认PTTG1的上游调控基因，并进一步研究该信号通路中的特异性相互作用。这将为口咽肿瘤的治疗提供新的途径。
