Decreased brain-expressed X-linked 4 (BEX4) expression promotes growth of oral squamous cell carcinoma

Background: brain-expressed x-linked (bex) 4 is a member of bex family. the functional role of bex4 in oral squamous cell carcinoma (oscc) remains unknown. methods: expression level of bex family members (bex1-5) in oscc tissues and the paired normal epithelial were examined. functions of epigenetic changes (dna methylation and histone modifications) on bex4 suppression in oscc were examined by zebularine and trichostatin a (tsa) treatment on oscc cell lines. lentivector containing full-length bex4 was used to generate oscc cell lines with stable bex4 expression. effects of bex4 expression on oscc proliferation were monitored with xcelligence rtca real-time cell analyzer. bex4-overexpressing cal27 was implanted into nude mice to evaluate the effects on tumor growth in vivo. the signaling pathways regulated by bex4 in oscc was explored using human whole-transcript expression microarray. results: among the 5 bex family members,bex1 and bex4 showed significant down-regulation in oscc (p < 0.001). bex3,in comparison,was overexpressed in the primary tumor. bex4 expression in oscc cell lines was re-activated after zebularine and tsa treatment. high bex4 expression could suppress proliferation of oscc in vitro. subcutaneous tumor volume of bex4-overexpressing cal27 was remarkably reduced in nude mice. microarray experiment showed that s100a family members (s100a7,s100a7a,s100a8,s100a9 & s100a12) might be the downstream targets of bex4 in oscc. conclusions: bex4 functions as tumor suppressor by inhibiting proliferation and growth of oral cancer. decreased bex4 contributes to the increased proliferative propensity of oscc. © 2016 gao et al.