Overexpression Of HOXC11 Promotes Proliferation And Invasion Of Head And Neck Squamous Cell Carcinoma By Regulating PPAR-? And NF-?B Pathways

Background and ObjectivesSeveral studies have documented the aberrant expression of HOX gene(Homeobox gene)family was occurred in various malignant tumor.One of the HOX family gene named HOXC11 have proven to be involved in malignant biology behaviors of cancer cells,which could be used as a promising biomarker for the diagnosis of carcinoma.However,there has been no detailed investigation of the clinical significance of HOXC11 in HNSCC(Head and neck squamous cell carcinoma).Therefore,further investigation is needed to confirm the role of HOXC11 in HNSCC and its underlying mechanisms.Methods1.Identification the expression of HOXC11 gene in head and neck squamous cell carcinoma.Real-time PCR,Western blotting and Immunohistochemistry experiment were used to detect the expression level of HOXC11 in HNSCC samples,and analyze the clinical prognosis of HNSCC patients combined with TCGA data.2.Functional analysis of HOXC11 gene in HNSCC in vitro and vivo.Silencing HOXC11 cell lines were constructed.CCK-8 method,plate clone formation assay,Transwell assy and soft agar assay were performed to observe the effect of HOXC11 on cell proliferation and invasion ability of head and neck squamous cells.Furthermore,we established an nude mice model of head and neck squamous cell and evaluated the HOXC11-mediated functionality in HNSCC.3.The molecular mechanisms of silencing HOXC11 gene in HNSCC.Luciferase reporter,Real-time PCR and Westen blotting assay were conducted to observe the effect of silencing HOXC11 on the activation or inhibition of NF-?B and PPAR-y pathway.Further analyzed the expression of HOXC11,PPAR-yand NF-?B in clinical HNSCC tissues by using immunohistochemistry to investigate their correlation.Results1.HOXC11 was significantly elevated in HNSCC by examining our clinical HNSCC tissues,which was positively correlated with T stage.Furthermore,HNSCC patients with high-expressed HOXC11 were closed related to poor prognosis and tumor recurrence.2.Silencing HOXC11 in HNSCCM cell could inhibit the proliferation and invasion ability of the tumor cells.3.Overexpression of HOXC11 promotes proliferation and migration in HNSCC by activating NF-?B pathway and inhibiting PPAR-? pathway,which positively associates with the downregulation of PPAR-y as well as the upregulation of nuclear p65.ConclusionThe evidence from this study suggests that overexpression of HOXC11 promotes tumor proliferation and migration in HNSCC,which was correlated with poor prognosis and tumor recurrence.In addition,silencing HOXC11 gene in HNSCC cells could inhibit the proliferation and invasion ability of the tumor cells by activating NF-?B pathway and inhibiting PPAR-y pathway.Therefore,it seems that HOXC11 is a promising biomarker as well as potential therapeutic target to be used in clinical and research.