Abstract
Circular RNAs (circRNAs) are a naturally occurring family of non-coding RNA that may regulate gene expression in mammals. circRNAs are more stable than messenger RNAs due to their resistance to RNA exonuclease. A growing body of evidence has shown that the expression of circRNAs is regulated during development in a tissue-specific manner. CircRNAs have been implicated in a number of cancers; however, their role in endometrial cancer (EC) is completely unknown. Here, we report the circular transcriptome specific for EC as determined by RNA sequencing. We found that the overall abundance of circRNAs is lower in EC than in normal endometrium. Further, there are numerous ‘hotspot’ genes from which circRNAs are transcribed that may account for alterations in circRNA expression between the normal and malignant endometrium. Most importantly, we have also identified circRNAs that are differentially expressed between malignant and normal endometrial tissue. The functional significance of these circRNAs in cancer remains to be determined, but they may serve as potential biomarkers for the diagnosis of EC or monitoring of EC progression.
Highlights
Endometrial cancer (EC) is the fifth most common cancer in women, accounting for 4.8% of all malignancies and 2.1% of all cancer-related deaths in women [1]
Using the same RNASeq data sets, we applied a computational pipeline which detects and tests differential expression of circRNAs between malignant and normal endometrial tissue. This is the first study of circular transcriptome profiling of endometrial cancer (EC) where we describe the circular transcriptome landscape, characterize features of circular transcripts expressed in EC, and detect differentially expressed circRNAs that may serve as potential biomarkers in EC diagnosis and progression monitoring
Through our analyses we have discovered that: 1) the overall abundance www.impactjournals.com/oncotarget of circRNAs is lower in EC than that of the normal endometrium; 2) most circRNAs are transcribed from exons in the endometrium; and 3) there are numerous ‘hotspot’ genes from which circRNAs are transcribed that may account for alterations in circRNA expression between the normal and malignant endometrium
Summary
Endometrial cancer (EC) is the fifth most common cancer in women, accounting for 4.8% of all malignancies and 2.1% of all cancer-related deaths in women [1]. Type I cancers are typically low stage and grade endometrioid histology that are positive for the estrogen and progesterone receptors, and strongly associated with obesity [3]. Type II cancers are usually estrogenindependent, advanced grade and stage endometrioid or clear-cell/serous histology, are not typically linked to obesity, and have a worse prognosis [3]. More recent investigations using next-generation sequencing technologies have facilitated a new evolution for the molecular classification of endometrial cancer. The TCGA project defines patients into categories that correlate with prognosis by 4 molecular subgroups including: (1) POLE (ultramutated), (2) microsatellite instability hypermutated, (3) copy-number low (microsatellite stable), and (4) copy-number high (serous-like) [4, 5], while the Leiden/TransPORTEC and Vancouver/ProMisE molecular classification systems have different risk stratification parameters to define molecular subgroups associated with prognosis [6]
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