P4HA2 通过 PI3K/AKT 信号通路促进头颈鳞状细胞癌的进展和 EMT。
P4HA2 contributes to head and neck squamous cell carcinoma progression and EMT through PI3K/AKT signaling pathway.
发表日期:2024 May 23
作者:
Yan-Ling Wu, Wan Liu, Tingting Zhao, Jing Jin
来源:
Cell Death & Disease
摘要:
头颈鳞状细胞癌(HNSCC)可以被定义为一种致命疾病,晚期预后不佳。因此,我们试图检查 P4HA2 在 HNSCC 中的表达和作用及其潜在机制。本研究利用综合生物信息学分析来评估 HNSCC 中 P4HA2 的表达模式、预后意义和可能的功能。该研究在人 HNSCC 细胞系 CAL-27 上进行了各种体外实验,包括集落形成、CCK-8、流式细胞术、伤口愈合和 Transwell 测定,以检查 P4HA2 在 HNSCC 进展中的参与情况。此外,使用蛋白质印迹法研究上皮间质转化 (EMT) 标记物和 PI3K/AKT 通路标记物,以阐明潜在的机制。 P4HA2 在 HNSCC 中表达显着增强,其过度表达与肿瘤侵袭性和患者不良预后相关。根据体外实验,过表达的P4HA2可增强细胞增殖、迁移、侵袭和EMT,同时减少细胞凋亡,而P4HA2沉默则表现出相反的效果。 P4HA2 过表达增强了 HNSCC 细胞中的 PI3K/AKT 磷酸化。此外,观察到 LY294002 可以抵消上调的 P4HA2 对 HNSCC 增殖、迁移、侵袭和 EMT 的影响。总的来说,我们表明 P4HA2 通过 PI3K/AKT 信号通路促进 HNSCC 进展和 EMT。© 2024。作者。
Head and neck squamous cell carcinoma (HNSCC) can be defined as a deadly illness with a dismal prognosis in advanced stages. Therefore, we seek to examine P4HA2 expression and effect in HNSCC, along with the underlying mechanisms. This study utilized integrated bioinformatics analyses to evaluate the P4HA2 expression pattern, prognostic implication, and probable function in HNSCC. The study conducted various in vitro experiments, including colony formation, CCK-8, flow cytometry, wound healing, and transwell assays, on the human HNSCC cell line CAL-27 to examine the involvement of P4HA2 in HNSCC progression. Moreover, western blotting was used to investigate epithelial-mesenchymal transition (EMT) markers and PI3K/AKT pathway markers to elucidate the underlying mechanisms. P4HA2 expression was significantly enhanced in HNSCC, and its overexpression was correlated to tumor aggressiveness and a poor prognosis in patients. Based on in vitro experiments, the overexpressed P4HA2 enhanced cell proliferation, migration, invasion, as well as EMT while reducing apoptosis, whereas P4HA2 silencing exhibited the reverse effect. P4HA2 overexpression enhanced PI3K/AKT phosphorylation in HNSCC cells. Moreover, LY294002 was observed to counteract the effects of upregulated P4HA2 on proliferation, migration, invasion, and EMT in HNSCC. Collectively, we indicated that P4HA2 promoted HNSCC progression and EMT via PI3K/AKT signaling pathway.© 2024. The Author(s).