Abstract
BackgroundLong non-coding RNAs (lncRNAs) are pervasively transcribed in the genome. They have important regulatory functions in chromatin remodeling and gene expression. Dysregulated lncRNAs have been studied in cancers, but their role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We have conducted lncRNA expression screening and a genome-wide analysis of lncRNA and coding gene expression on primary tumor and adjacent normal tissue from four ESCC patients, tend to understand the functionality of lncRNAs in carcinogenesis of esopheagus in combination with experimental and bioinformatics approach.MethodsLncRNA array was used for coding and non-coding RNA expression. R program and Bioconductor packages (limma and RedeR) were used for differential expression and co-expression network analysis, followed by independent confirmation and functional studies of inferred onco-lncRNA ESCCAL-1 using quantitative real time polymerase chain reaction, small interfering RNA-mediated knockdown, apoptosis and invasion assays in vitro.ResultsThe global coding and lncRNA gene expression pattern is able to distinguish ESCC from adjacent normal tissue. The co-expression network from differentially expressed coding and lncRNA genes in ESCC was constructed, and the lncRNA function may be inferred from the co-expression network. LncRNA ESCCAL-1 is such an example as a predicted novel onco-lncRNA, and it is overexpressed in 65% of an independent ESCC patient cohort (n = 26). More over, knockdown of ESCCAL-1 expression increases esophageal cancer cell apoptosis and reduces the invasion in vitro.ConclusionOur study uncovered the landscape of ESCC-associated lncRNAs. The systematic analysis of coding and lncRNAs co-expression network increases our understanding of lncRNAs in biological network. ESCCAL-1 is a novel putative onco-lncRNA in esophageal cancer development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1179-z) contains supplementary material, which is available to authorized users.
Highlights
Long non-coding RNAs are pervasively transcribed in the genome
LncRNAs are emerging as a novel class of noncoding RNAs that are pervasively transcribed in the genome [1], their expression profiling in esophageal squamous cell carcinoma (ESCC) has not been well investigated systematically
The genome-wide transcriptome including 7,419 intergenic Long non-coding RNAs (lncRNAs) along with 27,958 mRNAs were examined in ESCC and adjacent normal tissue
Summary
Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome. They have important regulatory functions in chromatin remodeling and gene expression. Dysregulated lncRNAs have been studied in cancers, but their role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. EC comprises of two different histopathological forms: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Recent high-throughput cancer genome sequencing revealed a handful of common known somatic gene mutations (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) and novel somatic gene mutations including chromatin modifying factors in EAC [10], and some previously undescribed gene mutations (ADAM29 and FAM135B) were detected in ESCC [11]. While most researches on esophageal cancer still focus on 2% of coding genes in the genome, lncRNA biology opens the door to understand more about the cancer initiatome which is the collective information of cellular malignant transformation [12]
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