PROX1 amplification predicts better prognosis of oral cancer and overexpression is associated with reduced tumor cell aggressiveness

Homeobox genes are a family of transcription factors that play a pivotal role in embryogenesis. Altered expression of Prospero-related homeobox gene 1 (PROX1) was recently associated with cancer, including oral squamous cell carcinoma (OSCC). This study aimed to investigate the functional role of PROX1 in oral carcinogenesis. PROX1 mRNA and protein expression levels were first investigated in 40 samples of OSCC and non-tumour margins. Methylation and amplification analysis was also performed to assess the epigenetic mechanisms involved in controlling PROX1 expression. OSCC cell line SCC9 was also transfected to stably express the PROX1 gene. Next, SCC9-PROX1-overexpressing cells and controls were then subjected to proliferation, differentiation, apoptosis, and microarray assays in vitro. OSCC samples had reduced PROX1 expression levels compared to non-tumour margins. PROX1 amplification was associated with better overall survival. PROX1 overexpression reduces cell proliferation by down-regulating cyclin D1 and up-regulating p21. PROX1-overexpressing cells also exhibited significantly reduced K18 and K19 expression. We analyzed the expression levels of PROX1 transcript and protein as well as PROX1 DNA amplification and methylation status in OSCC tissues and tumor-free surgical margins Additionally, we investigated the effects of PROX1 on cell proliferation, differentiation and survival following its overexpression in a squamous cell carcinoma cell line. Global gene expression profiling of cells overexpressing PROX1 was used as a means to comprehend mechanisms underlying these effects.