P4ha2 Promote Proliferation And Metastasis Of Hnscc

Prolyl 4-Hydroxylase Subunit Alpha 2 (P4HA2), a key enzyme in collagen post-translational modification, has been implicated in cancer progression. This study aimed to investigate the role of P4HA2 in head and neck squamous cell carcinoma (HNSCC), its correlation with hypoxia signaling, and its impact on tumor proliferation, metastasis, and extracellular matrix (ECM) remodeling. Using TCGA database and Kaplan-Meier survival analysis. Transcriptome sequencing and Western blot validated mRNA and protein levels of P4HA2 and COL1A1 in cancer and adjacent tissues. Hypoxia-inducible factor-1α (HIF-1α) regulation of P4HA2 was explored via ChIP-qPCR. Functional studies employed siRNA and overexpression plasmids to modulate P4HA2 expression in HNSCC cell lines, followed by assays for proliferation, migration, and invasion. Mechanistic insights were derived from pan-cancer analysis, pathway enrichment, and second harmonic generation (SHG) technology of collagen microstructure. P4HA2 expression was elevated in HNSCC tissues, correlating with poor survival. HIF-1α bound to the P4HA2 promoter under hypoxia, driving its transcription. Downregulating P4HA2 inhibited cell proliferation and metastasis, while upregulation enhanced these behaviors. P4HA2 activated the FAK-PI3K-AKT pathway, promoting collagen synthesis and ECM remodeling. SHG imaging revealed denser collagen fibers in high-P4HA2 tumors, whereas low-P4HA2 tumors exhibited looser collagen arrangements. P4HA2 is upregulated in HNSCC and promotes tumor progression by enhancing collagen synthesis, remodeling the ECM. Its association with hypoxia signaling and poor prognosis suggests P4HA2 as a potential therapeutic target for HNSCC.