BACKGROUND/AIMS: The lncRNA Homeobox (HOX) transcript antisense RNA (HOTAIR) is 
overexpressed in numerous cancers. HuR is also overexpressed during 
tumourigenesis and is abnormally present within the cytoplasm, where it binds to 
AU-rich elements in the 3'UTRs of target mRNA and post-transcriptionally 
regulates the expression of its target genes. However, whether HOTAIR is 
regulated and the mechanisms by which it affects head and neck squamous cell 
carcinoma (HNSCC) are not well understood.
METHODS: MTT, cell cycle arrest and apoptotic assays were used to examine the 
effects of HOTAIR and HuR on cell viability in SCC25 and FaDu cells. Wound 
healing and transwell invasion analysis were performed to detect the effects of 
HOTAIR and HuR on cell migration and invasion. The interaction between HuR and 
HOTAIR was confirmed via qRT-PCR, western blots, luciferase reporter and RIP 
assays. Finally, qRT-PCR analysis was used to detect the levels of HuR and 
HOTAIR in HNSCC tumours and adjacent normal tissues.
RESULTS: Knockdown of HOTAIR and HuR decreased cell viability, cellular 
migration and invasion. Moreover, HuR interacted and stabilized HOTAIR stability 
and thus promoted HOTAIR expression. Notably, HOTAIR acted as a miRNA sponge for 
HuR. HuR also reinforced HOTAIR sponge activity through miRNA recruitment, thus 
enhancing HuR expression in turn. Finally, HuR and HOTAIR levels were positively 
correlated and significantly up-regulated in tumours samples.
CONCLUSION: We demonstrated the existence of a regulatory loop in which the 
expression of HOTAIR and HuR is reciprocally and temporally regulated during the 
metastasis and progression of HNSCC.