Wang Yong, Hu Jianping, Chen Chen, Li Yongbo
Department of General Surgery, Suqian First Hospital, No. 120 Suzhi Road, Sucheng District, Suqian, Jiangsu Province, 223800, China.
Open Life Sci. 2024 Feb 8;19(1):20220813. doi: 10.1515/biol-2022-0813. eCollection 2024.
This study aimed to clarify the role of (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.
本研究旨在阐明垂体瘤转化基因1（PTTG1）在胰腺癌细胞增殖、迁移、侵袭及有氧糖酵解中的作用，并评估PTTG1作为治疗靶点的潜力。使用GEPIA数据库分析胰腺癌中PTTG1的表达情况。在PTTG1敲低的Panc1细胞或PTTG1过表达的Mia-PaCa2细胞中，通过细胞活力曲线和集落形成评估细胞增殖，分别进行伤口愈合试验和Transwell试验评估迁移和侵袭能力。此外，进行蛋白质免疫印迹法以评估PTTG1、增殖细胞核抗原、E-钙黏蛋白、N-钙黏蛋白和c-myc的表达。同时，分析葡萄糖摄取、细胞外酸化率（ECAR）和耗氧率（OCR）。我们的结果表明，胰腺癌中PTTG1表达上调，促进细胞增殖。低PTTG1水平有助于提高无病生存期和总生存期。在Panc1细胞中，PTTG1敲低导致细胞活力和集落形成减少。PTTG1敲低的Panc1细胞的迁移和侵袭能力也降低。相应地，PTTG1敲低降低了Panc1细胞中c-myc的表达、葡萄糖摄取、ECAR和OCR。在Mia-PaCa2细胞中，PTTG1过表达通过调节c-myc促进细胞增殖、有氧糖酵解以及β-连环蛋白向细胞核的转位。总之，PTTG1通过调节c-myc诱导胰腺癌细胞增殖、迁移和侵袭，并促进有氧糖酵解，表明PTTG1作为治疗靶点的潜力。
