PDF(Pubmed)
Abstract：
Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under physiological conditions. Although its overexpression influences a wide variety of malignant tumors\' occurrence and development, its specific effects and mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. This study focused on investigating the expression patterns, carcinogenic functions, and underlying mechanisms of P4HA2 in OSCC cells. Various databases, including TCGA, TIMER, UALCAN, GEPIA, and K-M plotter, along with paraffin-embedded samples, were used to ascertain P4HA2 expression in cancer and its correlation with clinicopathological features. P4HA2 knockdown and overexpression cell models were developed to assess its oncogenic roles and mechanisms. The results indicated that P4HA2 was overexpressed in OSCC and inversely correlated with patient survival. Knockdown of P4HA2 suppressed invasion, migration, and proliferation of OSCC cells both in vitro and in vivo, whereas overexpression of P4HA2 had the opposite effects. Mechanistically, the phosphorylation levels of the PI3K/AKT pathway were reduced following P4HA2 silencing. The study reveals that P4HA2 acts as a promising biomarker for predicting prognosis in OSCC and significantly affects metastasis, invasion, and proliferation of OSCC cells through the regulation of the PI3K/AKT signaling pathway.
摘要：
脯氨酸4-羟化酶2（P4HA2）以其羟化酶活性而闻名，主要参与在生理条件下羟基化胶原前体和促进胶原交联。尽管其过度表达影响多种恶性肿瘤的发生和发展，其在口腔鳞状细胞癌（OSCC）中的具体作用和机制尚不清楚。这项研究的重点是调查表达模式，致癌功能，以及P4HA2在OSCC细胞中的潜在机制。各种数据库,包括TCGA,TIMER,UALCAN,GEPIA,和K-M绘图仪，连同石蜡包埋的样本,用于确定P4HA2在癌症中的表达及其与临床病理特征的相关性。开发了P4HA2敲低和过表达细胞模型以评估其致癌作用和机制。结果表明，P4HA2在OSCC中过表达，与患者生存率呈负相关。敲除P4HA2抑制侵袭，迁移,和OSCC细胞在体外和体内的增殖，而P4HA2的过表达具有相反的作用。机械上,P4HA2沉默后,PI3K/AKT通路的磷酸化水平降低.该研究表明，P4HA2作为预测OSCC预后的有希望的生物标志物，并显著影响转移，入侵,通过PI3K/AKT信号通路调节OSCC细胞的增殖。
