Abstract
AbstractPlatelet factor-4 variant 1 (PF4V1) was recently described as a natural non-allelic gene variant of platelet factor-4 (PF4), which has been closely associated with the growth and metastasis of various cancers. Our previous research showed that PF4V1 was related to oral squamous cells carcinoma (OSCC) metastasis. Howerver, it is still not clear about the functional role of PF4V1 in OSCC. In this study, stably transfected cell lines were constructed and the expression level of PF4V1 was verified by real‐time polymerase chain reaction (RT-PCR) and western blot. The effect of PF4V1 on proliferation, migration, invasion, and apoptosis of oral cancer (OC) cells were detected. Moreover, a xenograft tumor model was constructed to evaluate the effect of PF4V1 on OSCC in vivo. Indicators of Wnt/β-catenin, angiogenesis and epithelial-mesenchymal transition (EMT) pathways were also examined. Stable cell lines with overexpression and inhibited expression of PF4V1 were constructed successfully. After stable transfection, PF4V1 significantly promoted the proliferation, migration, and invasion of OC cells in vitro, and their tumor formation in vivo. Furthermore, PF4V1 remarkably promoted the expression of β-catenin, VEGF, and FGF but suppressed the expression of GSK-3β. There was no statistically significant correlation between PF4V1 and EMT pathway. This study provides evidence that PF4V1 promotes the proliferation, migration, invasion and tumor formation of OC cells by regulating the Wnt/β-catenin pathway and angiogenesis. Our findings suggest that PF4V1 could be a very promising target of OSCC therapy in the future.
Funder
Guangxi Natural Science Foundation
Youth Science Foundation of Guangxi Medical University
Middle-aged and Young Teacher’s Basic Ability Promotion Project of Guangxi
Guangxi Clinical Research Center for Craniofacial Deformity
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Organic Chemistry,General Biochemistry, Genetics and Molecular Biology
Reference31 articles.
1. Rosebush MS, Rao SK, Samant S, Gu W, Handorf CR, Pfeffer LM et al (2011) Oral cancer: enduring characteristics and emerging trends. J Tenn Dent Assoc 91(2):24–27
2. Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4–5):309–316
3. Kumar SR, Markusic DM, Biswas M, High KA, Herzog RW (2016) Clinical development of gene therapy: results and lessons from recent successes. Mol Ther Methods Clin Dev 3:16034
4. Negre O, Eggimann AV, Beuzard Y, Ribeil JA, Bourget P, Borwornpinyo S et al (2016) Gene therapy of the beta-hemoglobinopathies by lentiviral transfer of the beta (A(T87Q))-globin gene. Hum Gene Ther 27(2):148–165
5. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS et al (2009) Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114(3):535–546
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献