Pseudo-WHAT? Investigating the Role of Tissue-Specific Pseudogenes in Breast Cancer

Abstract

Pseudogenes are an interesting paradigm in the human genome – they look like protein-coding genes but have lost functionality over time; yet, they remain in the human genome. Their retention suggests that they do have a purpose in regulating cellular processes within the body. Otherwise, evolution would have removed pseudogenes from the human genome long ago. Current estimates suggest that there are at least 20,000 pseudogenes throughout the genome, making them as abundant, if not more, as protein-coding genes. Research has shown that pseudogenes exhibit a tissue-specific pattern of expression under both normal and disease conditions. This observation posits the idea that these pseudogenes contribute to tumor development and progression by affecting not only the expression of its parental gene, but also of other protein-coding genes. The present study seeks to understand the potential mechanisms through which two pseudogenes, DPP3P2 and PGK1P2, function to increase the expression of the corresponding parental genes, DPP3 and PGK1, in breast cancer. This could manifest through either an RNA-mediated mechanism involving the pseudogene transcript or through a direct interaction between the pseudogene and parental gene. Furthermore, pseudogenes can also alter the expression of other protein-coding genes by binding and sequestering common miRNAs. In doing so, this study furthers the current knowledge of how the expression of pseudogenes in tumor tissues and cells drives tumorigenesis. Like other elements of the human genome, the role of pseudogenes is incredibly complex and adds another dimension to the understanding of tumor and cell biology. With further research, these pseudogenes may be a promising therapeutic target in the treatment of breast cancer.