Prediction of long noncoding RNA functions with co-expression network in esophageal squamous cell carcinoma

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.

Unraveling the oral cancer lncRNAome: Identification of novel lncRNAs associated with malignant progression and HPV infection

“…This suggests that these lncRNAs might play important and functional roles by regulating directly or indirectly key protein-coding gene expression that in turn may contribute to HNSCC. For example, CASC9 ( ESCCAL-1 ), which we identified in our analysis of HNSCC, was also overexpressed in esophageal SCC, where it functions as an onco-lncRNA through inhibition of apoptosis and promoting invasion in vitro [51]. …”

Upregulated long non-coding RNA SBF2-AS1 promotes proliferation in esophageal squamous cell carcinoma

“…lncRNAs are involved in every aspect of cellular processes, including cellular development, modulation of apoptosis, metastasis and parental imprinting (8)(9)(10). Emerging evidence suggests that the dysregulation of lncRNAs is linked to the development and metastasis in several types of cancer, including EC (11)(12)(13). The importance of lncRNAs in ESCC carcinogenesis has been recently evidenced.…”

A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

“…In case of esophageal cancer, the involvement of several lncRNAs in esophageal cancer and their underlying mechanisms have been reported 17, 18. For instance, the lncRNA cancer susceptibility candidate 9(CASC9) is significantly upregulated in ESCC tissues, and over‐expressed CASC9 promotes ESCC cells growth through interacting with EZH2 and repressing PDCD4 transcription 19.…”