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Updated: Apr 16, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Pseudogenes transcribed in breast invasive carcinoma show subtype-specific expression and ceRNA potential
Joshua D Welch1,2, Jeanette Baran-Gale3,4, Charles M Perou5,6,7
1Curriculum in Bioinformatics and Computational Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. jwelch@cs.unc.edu.
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.
Insights
Pseudogenes are transcribed and can act as competing endogenous RNAs (ceRNAs) in cancer. This study developed a new method to identify transcribed pseudogenes in breast cancer, revealing their widespread regulatory roles.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Pseudogenes are increasingly recognized for their roles in cancer when dysregulated.
- Pseudogene transcripts can function as competing endogenous RNAs (ceRNAs), but their study is limited by sequence similarity and lack of integrated miRNA data.
- Previous research on pseudogenes in breast cancer has not performed large-scale analysis of ceRNA potential by integrating miRNA expression data.
Purpose of the Study:
- To investigate the pervasive regulatory role of transcribed pseudogenes in cancer.
- To develop a novel bioinformatic method for measuring pseudogene transcription from RNA-seq data.
- To analyze the ceRNA potential of pseudogenes in breast cancer using integrated expression data.
Main Methods:
- Developed a novel bioinformatic method to quantify pseudogene transcription from RNA-seq data.
- Applied the method to 819 breast cancer samples from The Cancer Genome Atlas (TCGA).
- Integrated pseudogene, gene, and miRNA expression data with miRNA target prediction for ceRNA analysis.
Main Results:
- Identified 440 transcribed pseudogenes in breast cancer tissue, with 309 showing differential expression across subtypes.
- Pseudogene expression levels accurately separated tumor from normal samples and distinguished Basal from Luminal and Her2 subtypes.
- Found more significant pseudogene-parent gene correlations and pseudogene-miRNA anti-correlations than expected by chance, with 177 pseudogenes predicted to act as ceRNAs.
Conclusions:
- Pseudogene transcription is widespread in breast cancer and plays a significant regulatory role.
- The developed method enables large-scale analysis of pseudogene transcription and ceRNA potential.
- Results expand the catalog of putative pseudogene ceRNAs and highlight their underappreciated role in breast cancer.
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