Abstract
Background: Many pseudogenes possess biological activities and play important roles in the pathogenesis of various types of cancer including bladder cancer (BlCa), which still lacks suitable molecular biomarkers. Recently, pseudogenes were found to be significantly enriched in a pan-cancer classification based on the Cancer Genome Atlas gene expression data. Among them, the top-ranking pseudogene was the proliferation-associated 2G4 pseudogene 4 (PA2G4P4). Methods: Genomic and transcript features of PA2G4P4 were determined by GeneBank database analysis followed by 5’ RACE experiments. Therefore, we conducted a retrospective molecular study on a cohort of 45 patients of BlCa. PA2G4P4 expression was measured by RT-qPCR, whereas PA2G4P4 transcript distribution was analyzed by in situ hybridization on both normal and cancerous histological sections and compared to the immunolocalization of its parental PA2G4/EBP1 protein. Finally, we tested the effects of PA2G4P4 depletion on proliferation, migration, and death of BlCa cells. Results: We showed for the first time PA2G4P4 overexpression in BlCa tissues and in cell lines. PA2G4P4 distribution strictly overlaps PA2G4/EBP1 protein localization. Moreover, we showed that PA2G4P4 knockdown affects both proliferation and migration of BlCa cells, highlighting its potential oncogenic role. Conclusions: PA2G4P4 may play a functional role as an oncogene in BlCa development, suggesting it as a good candidate for future investigation and new clinical applications.
Highlights
Pseudogenes are evolutionally conserved and present in several organisms [1]
Discussion the first time on the proliferation-associated 2G4 pseudogene 4 (PA2G4P4) pseudogene, which has been recently identified as the most frequently appearing pseudogene in athe pan-cancer using
PA2G4P4 was very difficult to delimit, as this region shows high focused for the first time on the PA2G4P4 pseudogene, which has been recently identified as the most sequence similarity with five more pseudogenes associated with as well as with several frequently appearing pseudogene in a pan-cancer classification, using RNA-seq gene expression data coding and non-coding from the Cancer
Summary
Pseudogenes are evolutionally conserved and present in several organisms [1]. They derive from a retro-transposition event of a processed gene or from the degeneration of a duplicated gene.Over the last decades, data from large transcriptomic studies have shown that most pseudogenes are not “genomic relicts”, but are transcriptionally active and involved in important regulatoryBiology 2020, 9, 66; doi:10.3390/biology9040066 www.mdpi.com/journal/biologyBiology 2020, 9, 66 mechanisms [1]. Pseudogenes may act as positive or negative regulators of gene expression. Pseudogenes may compete with the parental genes for the same microRNAs or same destabilizing RNA-binding proteins, resulting in an increased level of the parental gene. Pseudogenes may compete for the same stabilizing RNA binding proteins or transcribe into endogenous siRNAs that can bind to any region of the parental genes [2,3]. Pseudogenes were found to be significantly enriched in a pan-cancer classification based on the Cancer Genome Atlas gene expression data. BlCa. PA2G4P4 expression was measured by RT-qPCR, whereas PA2G4P4 transcript distribution was analyzed by in situ hybridization on both normal and cancerous histological sections and compared to the immunolocalization of its parental PA2G4/EBP1 protein.
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