Aberrant DNA hypermethylation-silenced SOX21-AS1 gene expression and its clinical importance in oral cancer.

Cheng-Mei Yang,Ming-Chien Lee,Yu-Kai Tseng,Huei-Han Liou,Yow-Ling Shiue,Pei-Feng Liu,Luo-Ping Ger,Tsung-Han Wang,Kuo-Wang Tsai,Hung-Chih Chen,Sung-Chou Li

doi:10.1186/s13148-016-0291-5

Abstract

BackgroundLong 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.ResultsWe 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).ConclusionsSOX21-AS1 was identified as susceptible dysfunction correlated with promoter hypermethylation in OSCC. Low SOX21-AS1 expression may be an adverse prognostic biomarker for OSCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0291-5) contains supplementary material, which is available to authorized users.

Highlights

Long noncoding RNAs are more than 200 nucleotides in length and lack transcriptional ability
Long noncoding RNAs identified in oral squamous cell carcinoma (OSCC) tissues through next-generation sequencing Transcriptome profiles were comprehensively analyzed on laser capture microdissected tumors and corresponding adjacent normal tissues from two OSCC patients through a next-generation sequencing (NGS) approach
Dysregulated Long noncoding RNAs (lncRNAs) were selected from two OSCC patients and were highly expressed (RPKM of normal + RPKM of tumor > 5), and the fold change of RPKM was >3 or

Summary

Introduction

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. Oral squamous cell carcinoma (OSCC) is the most common oral cancer and 300,400 incident cases and 145,400 deaths have been reported worldwide [2]. Some lncRNAs, such as transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and spliceosomal RNAs, are crucial for maintaining normal cellular mechanisms [5]. Except for these functional lncRNAs, most lncRNAs have been frequently considered functionless sequences [6,7,8]. Fang et al reported that urothelial cancer associated 1 (UCA1) is an overexpression in tongue squamous cell carcinomas (TSCCs) and may play an oncogenic role in tumorigenesis [11]

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