HOXA10 promotes nasopharyngeal carcinoma cell proliferation and invasion via inducing the expression of ZIC2.

OBJECTIVE: In this study, we aimed to explore the dysregulated genes in nasopharyngeal carcinoma (NPC) and to investigate the regulative effect of HOXA10 on ZIC2 expression and their involvement in NPC cell proliferation and invasion.
MATERIALS AND METHODS: Microarray data that compared the transcription profile of NPC tissues and normal tissues was searched in GEO datasets and was re-analyzed. The expression of HOXA10 and ZIC2 mRNA were retrieved in TCGA database. CNE1 and CNE2 cells were used as an in-vitro cell model. Luciferase reporters carrying truncated ZIC2 promoter sequences were generated to verify the predicted HOXA10 binding site. CCK-8 assay and transwell assay were applied to assess cell proliferation and invasion respectively.
RESULTS: HOXC6, HOXA3, and HOXA10 were upregulated in NPC tissues. Data mining in TCGA database showed that HOXA10, but not HOXC6 or HOXA3 is positively correlated to ZIC2 expression. Enforced HOXA10 expression significantly elevated ZIC2 expression at both mRNA and protein levels in both CNE1 and CNE2 cells. HOXA10 can directly bind to the promoter of ZIC2 and upregulate ZIC2 transcription. ZIC2 knockdown significantly reduced cell proliferation and invasion capability of CNE1 cells and also partly abrogated the effect of HOXA10 overexpression on enhancing cell proliferation and invasion.
CONCLUSIONS: Both HOXA10 and ZIC2 are upregulated in NPC tissues compared to the normal tissues. HOXA10 can increase ZIC2 expression via binding to the ZIC2 promoter. Functionally, the HOXA10-ZIC2 axis can enhance NPC cell proliferation and invasion.