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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.
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Details
1 Qingdao Huangdao District Central Hospital, Department of Stomatology, Qingdao, China
2 University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital), Department of Stomatology, Qingdao Hospital, Qingdao, China (GRID:grid.415468.a) (ISNI:0000 0004 1761 4893)
3 Changchun University of Chinese Medicine, Acupuncture and Tuina Department, Changchun, Jilin, China (GRID:grid.440665.5) (ISNI:0000 0004 1757 641X)
4 Qingdao Huangdao District Central Hospital, Department of Stomatology, Qingdao, China (GRID:grid.440665.5)
5 Sun Yat-sen University, Department of Stomatology, Shenzhen-Shanwei Central Hospital, Shanwei, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X)
6 Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Department of Oromaxillofacial Head and Neck Oncology, College of Stomatology, Shanghai, China (GRID:grid.412523.3) (ISNI:0000 0004 0386 9086)
7 Binzhou Medical University, Institute of Stomatology, Binzhou, China (GRID:grid.440653.0) (ISNI:0000 0000 9588 091X); Binzhou Medical University, The affiliated Yantai Stomatological Hospital, Binzhou, China (GRID:grid.440653.0) (ISNI:0000 0000 9588 091X)