Pseudogenes transcribed in breast invasive carcinoma show subtype-specific expression and ceRNA potential
Year: 2015
Type: article
Abstract: BACKGROUND: Recent studies have shown that some pseudogenes are transcribed and contribute to cancer when dysregulated. In particular, pseudogene transcripts can function as competing endogenous RNAs (ceRNAs). The high similarity of gene and pseudogene nucleotide sequence has hindered experimental investigation of these mechanisms using RNA-seq. Furthermore, previous studies of pseudogenes in breast cancer have not integrated miRNA expression data in order to perform large-scale analysis of ceRNA potential. Thus, knowledge of both pseudogene ceRNA function and the role of pseudogene expression in cancer are restricted to isolated examples. RESULTS: To investigate whether transcribed pseudogenes play a pervasive regulatory role in cancer, we developed a novel bioinformatic method for measuring pseudogene transcription from RNA-seq data. We applied this method to 819 breast cancer samples from The Cancer Genome Atlas (TCGA) project. We then clustered the samples using pseudogene expression levels and integrated sample-paired pseudogene, gene and miRNA expression data with miRNA target prediction to determine whether more pseudogenes have ceRNA potential than expected by chance. CONCLUSIONS: Our analysis identifies with high confidence a set of 440 pseudogenes that are transcribed in breast cancer tissue. Of this set, 309 pseudogenes exhibit significant differential expression among breast cancer subtypes. Hierarchical clustering using only pseudogene expression levels accurately separates tumor samples from normal samples and discriminates the Basal subtype from the Luminal and Her2 subtypes. Correlation analysis shows more positively correlated pseudogene-parent gene pairs and negatively correlated pseudogene-miRNA pairs than expected by chance. Furthermore, 177 transcribed pseudogenes possess binding sites for co-expressed miRNAs that are also predicted to target their parent genes. Taken together, these results increase the catalog of putative pseudogene ceRNAs and suggest that pseudogene transcription in breast cancer may play a larger role than previously appreciated.
Source: BMC Genomics
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,090
Awards: G1569999668, G2313650546, G2407663899, G3739017323, G397544877, G407219290, Predoctoral Training Program in Bioinformatics and Computational Biology, Exon Splice Pattern Characterization of the Whole mRNA Transcriptome, G4753454313, G5072299758, Graduate Reserach Fellowship Program (GRFP), Discovery of microRNA regulatory modules controlling human pancreatic islet funct, G870117454, G9000021974, G9000073604, G9000182874
OpenAlex ID: W2123250375