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SPLUNC 1 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
Author(s) -
Zhang Wenling,
Zeng Zhaoyang,
Wei Fang,
Chen Pan,
Schmitt David C.,
Fan Songqing,
Guo Xiaofang,
Liang Fang,
Shi Lei,
Liu Zixin,
Zhang Zuping,
Xiang Bo,
Zhou Ming,
Huang Donghai,
Tang Ke,
Li Xiaoling,
Xiong Wei,
Tan Ming,
Li Guiyuan,
Li Xiayu
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13020
Subject(s) - nasopharyngeal carcinoma , retinoic acid , gene knockdown , retinoic acid receptor , cancer research , tretinoin , retinoic acid receptor alpha , retinoic acid receptor beta , biology , receptor , retinoic acid inducible orphan g protein coupled receptor , cancer , chemistry , microbiology and biotechnology , medicine , apoptosis , gene , biochemistry , genetics , radiation therapy
Human SPLUNC 1 can suppress nasopharyngeal carcinoma ( NPC ) tumor formation; however, the correlation between SPLUNC 1expression and NPC patient prognosis has not been reported. In the present study, we used a large‐scale sample of 1015 tissue cores to detect SPLUNC 1 expression and its association with patient prognosis. SPLUNC 1 expression was reduced in NPC samples compared to nontumor nasopharyngeal epithelium tissues. Positive expression of SPLUNC 1 in NPC predicted a better prognosis (disease‐free survival, P = 0.034; overall survival, P = 0.048). Cox's proportional hazards model revealed that SPLUNC 1 could be a significant prognostic factor affecting disease‐free survival ( P = 0.027). A c DNA micro‐array analyzed by significant analysis of micro‐array (SAM) and ingenuity pathway analysis (IPA) revealed that an indirect interaction existed between SPLUNC 1 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 SPLUNC 1 gene. The transcriptional activity of the SPLUNC 1 promoter was up‐regulated significantly by all‐trans‐retinoic acid ( ATRA ). SPLUNC 1 and retinoic acid receptor expression were induced significantly by ATRA , and removal of ATRA led to a progressive loss of SPLUNC 1 and retinoic acid receptor expression. ATRA inhibited proliferation and induced the differentiation of NPC cells. Interestingly, over‐expression of SPLUNC 1 sensitized NPC cells to ATRA , whereas knockdown of SPLUNC 1 in HNE 1 cells increased cell viability. Under SPLUNC 1 knockdown conditions, differentiation was reversed by ATRA treatment. We concluded that SPLUNC 1 could potentially predict prognosis for NPC patients and play an important role in ATRA ‐induced growth inhibition and differentiation in NPC cells.