PF4V1, an miRNA-875-3p target, suppresses cell proliferation, migration, and invasion in prostate cancer and serves as a potential prognostic biomarker
Received 17 September 2018
Accepted for publication 31 December 2018
Published 21 March 2019 Volume 2019:11 Pages 2299—2312
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 4
Editor who approved publication: Dr Rituraj Purohit
Dongyang Li,1 Xuanyu Hao,2 Yudi Dong,3 Mo Zhang,1 Yongsheng Song1
1Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Laboratory of Experimental Oncology, Medical Research Center, Shengjing Hospital of China Medical University, Benxi, Liaoning, People’s Republic of China
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
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