SPLUNC1 is associated with nasopharyngeal carcinoma prognosis and plays an important role in all-trans-retinoic acid-induced growth inhibition and differentiation in nasopharyngeal cancer cells.

Human SPLUNC1 can suppress nasopharyngeal carcinoma (NPC) tumor formation; however, the correlation between SPLUNC1expression and NPC patient prognosis has not been reported. In the present study, we used a large-scale sample of 1015 tissue cores to detect SPLUNC1 expression and its association with patient prognosis. SPLUNC1 expression was reduced in NPC samples compared to nontumor nasopharyngeal epithelium tissues. Positive expression of SPLUNC1 in NPC predicted a better prognosis (disease-free survival, P = 0.034; overall survival, P = 0.048). Cox's proportional hazards model revealed that SPLUNC1 could be a significant prognostic factor affecting disease-free survival (P = 0.027). A cDNA micro-array analyzed by significant analysis of micro-array (SAM) and ingenuity pathway analysis (IPA) revealed that an indirect interaction existed between SPLUNC1 and retinoic acid (RA) in the cancer regulatory network. To further investigate the molecular mechanisms involved, we utilized several bioinformatics tools and identified 12 retinoid X receptors heterodimer binding sites in the promoter region of the SPLUNC1 gene. The transcriptional activity of the SPLUNC1 promoter was up-regulated significantly by all-trans-retinoic acid (ATRA). SPLUNC1 and retinoic acid receptor expression were induced significantly by ATRA, and removal of ATRA led to a progressive loss of SPLUNC1 and retinoic acid receptor expression. ATRA inhibited proliferation and induced the differentiation of NPC cells. Interestingly, over-expression of SPLUNC1 sensitized NPC cells to ATRA, whereas knockdown of SPLUNC1 in HNE1 cells increased cell viability. Under SPLUNC1 knockdown conditions, differentiation was reversed by ATRA treatment. We concluded that SPLUNC1 could potentially predict prognosis for NPC patients and play an important role in ATRA-induced growth inhibition and differentiation in NPC cells.

Zhang W ，Zeng Z ，Wei F ，Chen P ，Schmitt DC ，Fan S ，Guo X ，Liang F ，Shi L ，Liu Z ，Zhang Z ，Xiang B ，Zhou M ，Huang D ，Tang K ，Li X ，Xiong W ，Tan M ，Li G ，Li X ... -  《-》

APLNR is involved in ATRA-induced growth inhibition of nasopharyngeal carcinoma and may suppress EMT through PI3K-Akt-mTOR signaling.

Liu Y ，Liu Q ，Chen S ，Liu Y ，Huang Y ，Chen P ，Li X ，Gao G ，Xu K ，Fan S ，Zeng Z ，Xiong W ，Tan M ，Li G ，Zhang W ... -  《-》

SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway.

Ou C ，Sun Z ，Zhang H ，Xiong W ，Ma J ，Zhou M ，Lu J ，Zeng Z ，Bo X ，Chen P ，Li G ，Li X ，Li X ... -  《-》

Intracellular co-localization of SPLUNC1 protein with nanobacteria in nasopharyngeal carcinoma epithelia HNE1 cells depended on the bactericidal permeability increasing protein domain.

Zhou HD ，Li GY ，Yang YX ，Li XL ，Sheng SR ，Zhang WL ，Zhao J ... -  《MOLECULAR IMMUNOLOGY》

Transcriptional up-regulation of restin by all-trans retinoic acid through STAT1 in cancer cell differentiation process.

Fu H ，Yang G ，Lu F ，Wang R ，Yao L ，Lu Z ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》