title: Aberrant DNA hypermethylation-silenced SOX21-AS1 gene expression and its clinical importance in oral cancer.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan ; Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: Cheng-Mei
authors.initials: CM
authors.lastname: Yang
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813 Taiwan ; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan ; Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Sung-Chou
authors.initials: SC
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Chien
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813 Taiwan.
authors.forename: Huei-Han
authors.initials: HH
authors.lastname: Liou
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813 Taiwan ; Department of Biotechnology, Fooyin University, Kaohsiung, Taiwan.
authors.forename: Pei-Feng
authors.initials: PF
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan ; Department of Orthopedics, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Yu-Kai
authors.initials: YK
authors.lastname: Tseng
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Yow-Ling
authors.initials: YL
authors.lastname: Shiue
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813 Taiwan ; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Luo-Ping
authors.initials: LP
authors.lastname: Ger
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813 Taiwan ; Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan.
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D062085:RNA, Long Noncoding; C000617875:long noncoding RNA SOX21-AS1, human
keywords: DNA methylation; LncRNA; Next-generation sequencing; Oral cancer; SOX21; SOX21-AS1