2. Academic Validation
  3. P4HA2 promotes proliferation, invasion, and metastasis through regulation of the PI3K/AKT signaling pathway in oral squamous cell carcinoma

P4HA2 promotes proliferation, invasion, and metastasis through regulation of the PI3K/AKT signaling pathway in oral squamous cell carcinoma

  • Sci Rep. 2024 Jul 1;14(1):15023. doi: 10.1038/s41598-024-64264-5.
Zengpeng Chi # 1,  Qimin Wang # 2,  Xin Wang 3,  Dagang Li 1,  Lei Tong 2,  Yu Shi 4,  Fang Yang 2,  Qingyuan Guo 2,  Jiawei Zheng 5,  Zhenggang Chen 6 7
Affiliations

Affiliations

  • 1 Department of Stomatology, Qingdao Huangdao District Central Hospital, Qingdao, 266555, China.
  • 2 Department of Stomatology, Qingdao Hospital, University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital), No.5 Donghai Middle Road, Qingdao, 266071, China.
  • 3 Acupuncture and Tuina Department, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China.
  • 4 Department of Stomatology, Shenzhen-Shanwei Central Hospital, Sun Yat-sen University, Shanwei, 516699, China.
  • 5 Department of Oromaxillofacial Head and Neck Oncology, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Manufacturing Bureau Road, Huangpu District, Shanghai, 200011, China. davidzhengjw@hotmail.com.
  • 6 Institute of Stomatology, Binzhou Medical University, 256600, Binzhou, China. chenzhg1973@163.com.
  • 7 The affiliated Yantai Stomatological Hospital, Binzhou Medical University, 264000, Binzhou, China. chenzhg1973@163.com.
  • # Contributed equally.
PMID: 38951593 DOI: 10.1038/s41598-024-64264-5
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.

Keywords

Invasion; Migration; P13K/AKT pathway; P4HA2; Proliferation.

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