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Abstract：
This study aimed to clarify the role of pituitary tumor-transforming gene 1 (PTTG1) in proliferation, migration, invasion, and aerobic glycolysis of pancreatic cancer cells, and evaluate the potential of PTTG1 as a therapeutic target. PTTG1 expression in pancreatic cancers was analyzed using the GEPIA databank. In the Panc1 cell with the PTTG1 knockdown or Mia-PaCa2 cells with PTTG1 overexpression, the cell proliferation was evaluated using cell viability curves and colony formation, and wound heal assay and transwell assay were performed to evaluate the migration and invasion, respectively. Furthermore, a western blot was performed to evaluate the expressions of PTTG1, proliferating cell nuclear antigen, E-cadherin, N-cadherin, and c-myc. Meanwhile, the glucose uptake, extracellular acidification rates (ECAR), and oxygen consumption rates (OCR) were analyzed. Our results showed that PTTG1 expression is upregulated in pancreatic cancer, which promoted cell proliferation. Low PTTG1 contributed to higher disease-free survival and overall survival. In Panc1 cell, PTTG1 knockdown resulted in reduced cell viability and colony formation. The migration and invasion abilities of the cells were also reduced in Panc1 with PTTG1 knockdown. Correspondingly, PTTG1 knockdown decreased c-myc expression, glucose uptake, ECAR, and OCR in Panc1 cells. In Mia-PaCa2 cells, PTTG1 overexpression promoted cell proliferation, aerobic glycolysis, and translocation of β-catenin to the nucleus by regulating c-myc. In conclusion, PTTG1 induces proliferation, migration, and invasion, and promotes aerobic glycolysis in pancreatic cancer cells via regulating c-myc, demonstrating the potential of PTTG1 as a therapeutic target.
摘要：
本研究旨在阐明垂体肿瘤转化基因1(PTTG1)在细胞增殖中的作用,迁移,入侵,和胰腺癌细胞的有氧糖酵解，并评估PTTG1作为治疗靶标的潜力。使用GEPIA数据库分析胰腺癌中的PTTG1表达。在PTTG1敲低的Panc1细胞或PTTG1过表达的Mia-PaCa2细胞中，使用细胞活力曲线和集落形成评估细胞增殖，并进行伤口愈合试验和transwell试验以评估迁移和侵袭，分别。此外，进行蛋白质印迹以评估PTTG1，增殖细胞核抗原，E-cadherin,N-钙黏着蛋白,c-myc同时,葡萄糖的摄取，细胞外酸化率（ECAR），分析了耗氧率(OCR)。我们的结果显示PTTG1在胰腺癌中表达上调,促进细胞增殖。低PTTG1有助于更高的无病生存率和总生存率。在Panc1单元格中，PTTG1敲低导致细胞活力和集落形成降低。在PTTG1敲低的Panc1中，细胞的迁移和侵袭能力也降低。相应地,PTTG1敲低降低c-myc表达，葡萄糖摄取，ECAR,和Panc1细胞中的OCR。在Mia-PaCa2细胞中，PTTG1过表达促进细胞增殖，有氧糖酵解，通过调节c-myc将β-catenin转位到细胞核。总之,PTTG1诱导增殖，迁移,和入侵,并通过调节c-myc促进胰腺癌细胞的有氧糖酵解，证明PTTG1作为治疗靶标的潜力。
