Abstract
Circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, have been shown to have important roles in a number of diseases, including several types of cancers. We hypothesized that circRNAs are involved in the pathogenesis of hypopharyngeal squamous cell carcinoma (HSCC). To test our hypothesis, we initially compared the expression profiles of circRNAs in 4 paired HSCC and adjacent normal tissue samples by using a circRNA microarray. The microarray data showed that 2392 circRNAs, including 1304 upregulated and 1088 downregulated circRNA transcripts, were significantly dysregulated in the HSCC tissues. The 10 most dysregulated circRNAs from the microarray analysis were further validated in another 32 pairs of specimens using quantitative real-time polymerase chain reaction assays. These circRNAs might sponge microRNAs (miRNAs) in predicted circRNA-miRNA-mRNA networks. Bioinformatics analysis was also performed to predict possible pathways in which these networks might be involved. Finally, we analyzed the interaction between validated circRNAs and their potential cancer-related miRNA targets. We are the first to comprehensively delineate the expression profiles of circRNAs in HSCC and to provide potential candidates for future mechanism studies. Our study is potentially of critical significance in uncovering the roles of circRNAs in HSCC.
Highlights
Hypopharyngeal squamous cell carcinoma (HSCC) is characterized by poor differentiation and early metastasis and is one of the most aggressive head and neck squamous cell carcinomas
We hypothesized that circular RNA (circRNA) are involved in the pathogenesis of hypopharyngeal squamous cell carcinoma (HSCC)
A total of 87,935 circRNA targets were detected in the four paired HSCC tumor and adjacent normal tissues
Summary
Hypopharyngeal squamous cell carcinoma (HSCC) is characterized by poor differentiation and early metastasis and is one of the most aggressive head and neck squamous cell carcinomas. CircRNAs have been found to sequester miRNAs [10,11,12] and regulate alternative splicing or transcription processes [13] as well as parental gene expression [7]. In addition to functioning as a miRNA sponge in mechanisms of circRNAs, other still unknown function of circRNAs, such as regulating alternative splicing, transcription or the expression of parental gene may contribute to the progression of HSCC. A growing number of circRNAs are aberrantly expressed in colorectal cancer [14], hepatocellular carcinoma [15, 16], gastric cancer [17], and laryngeal squamous cell carcinoma [18] and have the potential to become new diagnostic or prognostic biomarkers. The molecular mechanisms of some circRNAs and their clinical significance in cancers have been investigated [11, 12, 19]
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