BACKGROUND: Long noncoding RNAs (lncRNAs) are more than 200 nucleotides in 
length and lack transcriptional ability. The biological function of lncRNAs in 
oral squamous cell carcinoma (OSCC) remains unclear. The aim of this study was 
to identify the dysfunction of lncRNA in OSCC.
RESULTS: We analyzed the transcriptome profiles of human OSCC tissues and paired 
adjacent normal tissues from two patients through a next-generation sequencing 
approach. A total of 14 lncRNAs were upregulated (fold change ≥3) and 13 were 
downregulated (fold change ≤-3) in OSCC tissues compared with the adjacent 
normal tissues. SOX21-AS1 was subjected to further analysis, revealing that the 
expression levels of SOX21-AS1 significantly decreased in OSCC compared with the 
adjacent normal tissue. The promoter activity of SOX21-AS1 was obviously 
suppressed by in vitro methylation. The DNA methylation status of the SOX21-AS1 
promoter was analyzed using combined bisulfite restriction analysis, revealing 
that the aberrant promoter hypermethylation of SOX21-AS1 was observed frequently 
in OSCC tissues. The effects of SOX21-AS1 on cell proliferation and invasion 
were examined through transient transfection. Our data showed that SOX21-AS1 
could significantly suppress oral cancer cell growth and invasion. Furthermore, 
the low expression level of SOX21-AS1 was significantly correlated with an 
advanced stage (P = 0.047), large tumor size (P = 0.033), and poor 
disease-specific survival in OSCC patients (P = 0.002).
CONCLUSIONS: SOX21-AS1 was identified as susceptible dysfunction correlated with 
promoter hypermethylation in OSCC. Low SOX21-AS1 expression may be an adverse 
prognostic biomarker for OSCC.