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



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.



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.



BEX4 functions as tumor suppressor by inhibiting proliferation and growth of oral cancer. Decreased BEX4 contributes to the increased proliferative propensity of OSCC.
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
Wei
W
Gao
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.|Department of Otolaryngology, The First People's Hospital of Foshan, Foshan, Guangdong Province, China.
John Zeng-Hong
JZ
Li
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
Si-Qi
SQ
Chen
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
Chiao-Yun
CY
Chu
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
Jimmy Yu-Wai
JY
Chan
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China. thainsze@gmail.com.
Thian-Sze
TS
Wong
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics*; D009418:S100 Proteins / Q000235:genetics*
C000623207:BEX4 protein, human; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; D009418:S100 Proteins
BEX4; Brain-expressed X-linked family; Oral cancer; S100A family; Squamous cell carcinoma; Tumor growth