Abstract
Cancer-specific pseudogene expression may contribute to tumor progression.
Major finding: Cancer-specific pseudogene expression may contribute to tumor progression.
Approach: RNA-seq reads that mapped to unannotated regions were used for pseudogene expression analysis.
Impact: Pseudogene expression should be considered in genome-wide expression studies of cancer cells.
Ancestral copies of almost every protein-coding gene are found throughout the human genome. Called pseudogenes, these loci arose from genomic duplication or retrotransposition and generally lost their protein-coding ability through the accumulation of mutations. Emerging evidence suggests that pseudogenes may regulate expression of their corresponding wild-type genes by serving as a source of siRNAs, antisense transcripts, microRNA binding sites, or competing mRNAs. Identifying pseudogenes and measuring their expression has been hindered by the high degree of sequence similarity between pseudogenes and their cognate wild-type genes. Kalyana-Sundaram and colleagues devised a method to characterize pseudogene expression using paired-end RNA-seq data collected from 293 samples representing cancerous and normal tissues. Briefly, sequences with mismatches to reference genes mapping to unannotated genomic regions were considered putative pseudogenes, and the number of reads clustering at such loci was used as a measure of pseudogene expression. The authors identified 2,082 expressed pseudogenes, 576 of which had not been previously indexed. Many pseudogenes were ubiquitously or near-ubiquitously expressed and corresponded to housekeeping genes, and still others appeared to be tissue or lineage specific. Notably, 218 pseudogenes were only expressed in cancer samples, 40 of which were restricted to a single cancer type. For example, CXADR-ψ (ψ denotes a pseudogene) and ATP8A2-ψ were specifically upregulated in approximately 25% of prostate and breast cancer samples, respectively. Further analysis of ATP8A2-ψ showed that its knockdown inhibited proliferation, invasion, and migration of overexpressing cell lines in vitro and reduced intravasation and metastasis in vivo, and its overexpression stimulated the proliferation and migration of benign cells. These findings suggest that pseudogene expression is prevalent and may contribute to cancer progression, and thus it should be considered in analyses of cancer transcriptomes.
Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
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