Transcription factor SOX-5 enhances nasopharyngeal carcinoma progression by down-regulating SPARC gene expression
Journal
Journal of Pathology
Journal Volume
214
Journal Issue
4
Pages
445-455
Date Issued
2008
Author(s)
Abstract
Nasopharyngeal carcinoma (NPC) is prevalent in south-eastern Asia, and its tumourigenesis is rather complex. The purpose of this research was to identify the pivotal genes that may be altered during the early stage of NPC progression. Eleven genes were selected by comparative microarray analysis of NPC versus normal nasomucosal cells. The expression of SPARC (secreted protein, acidic, cysteine-rich) was statistically significantly down-regulated in NPC cells. In exploring the mechanism underlying the decreased transcription of SPARC in NPC cells, we found that the transcription factor SRY (sex-determining region Y)-box 5 (SOX-5) is up-regulated in NPC cells. RNA interference of SOX-5 by short hairpin RNA (shRNA) in NPC cells caused a dramatic increase in SPARC and chromosome immunoprecipitation assay showed that SOX-5 can bind directly to the SPARC promoter, suggesting that SOX-5 acts as a key transcriptional repressor of SPARC. We further demonstrated that shRNA knockdown of SOX-5 suppressed the proliferation of NPC cells, as well as their migratory ability, which was also observed when SPARC was over-expressed in NPC cells. Alternatively, blocking SPARC with an antagonistic antibody reversed the effects of SOX-5 knockdown. In 66 NPC patients, over-expression of SOX-5 in tumour cells correlated clinically with poor survival. Our study suggests that SOX-5 transcriptionally down-regulates SPARC expression and plays an important role in the regulation of NPC progression. SOX-5 is a potential tumour marker for poor NPC prognosis. Copyright ? 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
SDGs
Other Subjects
fibroblast growth factor receptor 1; protein; secreted protein acidic cysteine rich; short hairpin RNA; transcription factor Sox5; unclassified drug; animal experiment; animal model; animal tissue; article; cancer growth; carcinoma cell; cell migration; cell proliferation; cell survival; chromatin immunoprecipitation; chromosome; controlled study; down regulation; early cancer; gene expression regulation; gene identification; gene overexpression; genetic transcription; human; human cell; microarray analysis; mouse; nasopharynx carcinoma; nonhuman; priority journal; prognosis; RNA interference; statistical significance; transcription regulation; upregulation; Animals; Binding Sites; Disease Progression; DNA-Binding Proteins; Down-Regulation; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, SCID; Nasopharyngeal Neoplasms; Neoplasm Proteins; Neoplasm Transplantation; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Osteonectin; Prognosis; Promoter Regions (Genetics); Protein Isoforms; Proto-Oncogene Proteins; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Transcription Factors; Transplantation, Heterologous; Tumor Cells, Cultured; Tumor Markers, Biological
Type
journal article