PF4V1, an miRNA-875-3p target, suppresses cell proliferation, migration, and invasion in prostate cancer and serves as a potential prognostic biomarker

Background: PF4V1 is a novel protein in inflammation, angiogenesis, and Cancer. However, the pathogenesis, underlying mechanisms, and the prognostic value of PF4V1 in prostate Cancer (PCa) are still unclear.

Materials and methods: The PF4V1 expression and relation with survival were analyzed based on a large sample size in the Cancer Genome Atlas. In vitro, the overexpression of PF4V1 was conducted in DU145 and LNCaP cells. Cell Counting Kit-8, colony formation, wound healing, and Transwell^® assays were preformed to test biological functions of PF4V1 and miR-875-3p in PCa. Western blotting was used to measure downstream markers in Akt pathways and epithelial-mesenchymal transition (EMT). In vivo experiments were performed to test the therapeutic effect of PF4V1 protein to PCa via a mouse model.

Results: The expression of PF4V1 was significantly lower in 497 PCa samples than in 52 normal controls (P=0.0012). High PF4V1 expression (normalized by TP53) was associated with poor disease-free survival (DFS) and good overall survival (OS) in PCa (P<0.05). PF4V1 was underexpressed in four PCa cell lines than in normal prostate cells. Overexpression of PF4V1 could significantly suppress the proliferation, migration, and invasion of DU145 and LNCaP cells (P<0.05). Moreover, miR-875-3p targeted the 3'-untranslated region of PF4V1 and derepressed the inhibitory function of PF4V1 in PCa (P<0.05). Key proteins such as p-AKT/p-ERK/Snail/Slug/N-Cadherin were downregulated, while E-cadherin was upregulated when PF4V1 was overexpressed in PCa cells. Finally, intratumoral injection of PF4V1 protein could significantly inhibit PCa growth in vivo.

Conclusion: PF4V1 can suppress the proliferation, migration, and invasion of PCa cells by regulating Akt/ERK pathways and EMT. Elevated PF4V1/TP53 expression is correlated with poorer DFS and better OS in the patients with PCa. The miR-875-3p-PF4V1 axis may be a new therapeutic target site in PCa.

PF4V1; miR-875-3p; prostate cancer; survival.