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

Abstract

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.

Keywords:

• PF4V1
• miR-875-3p
• prostate cancer
• survival

Supplementary material

Table S1 Relationship between PF4V1 and clinical/pathological parameters of prostate cancer

Acknowledgments

We would like to thank Professor Zhijie Li (Medical Research Center, Shengjing Hospital) for her instruction and assistance in laboratory techniques. This study was supported by the Chinese National Natural Science Foundation (Program No. 81802540), Shenyang Government Science and Technology Plan Projects (Program No. F15-199-1-47), and the Excellent PhD Program of Shengjing Hospital of China Medical University (Program No. MF18).

Disclosure

The authors report no conflicts of interest in this work.