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Cell Cycle (Georgetown, Tex.) Sep 2020Latest studies have shown that deregulated pseudogene transcripts contribute to cancer working as competing endogenous RNAs. Our research group has recently demonstrated...
Latest studies have shown that deregulated pseudogene transcripts contribute to cancer working as competing endogenous RNAs. Our research group has recently demonstrated that the overexpression of two pseudogenes, and , has a critical role in cancer progression. These pseudogenes work sustaining the expression of HMGA1 and other cancer-related genes. We generated a mouse model overexpressing to better study the -pseudogene function in a more physiological context. Here, we show the proliferation rate and the susceptibility to senescence of mouse embryonic fibroblasts obtained from -overexpressing mice to better characterize the HMGA1-pseudogene function. Indeed, our study reports that mouse embryonic fibroblasts (MEFs) derived from mice express higher HMGA1 mRNA and protein levels. Moreover, these cells grow faster and senesce later than wild-type sustaining the oncogenic role of ceRNA crosstalk mediated by .
Topics: Animals; Cell Proliferation; Cells, Cultured; Cellular Senescence; Embryo, Mammalian; Fibroblasts; HMGA1a Protein; Humans; Mice, Transgenic; Pseudogenes; Up-Regulation
PubMed: 32787507
DOI: 10.1080/15384101.2020.1807080 -
Cell Cycle (Georgetown, Tex.) 2014Two pseudogenes for HMGA1, whose overexpression has a critical role in cancer progression, have been identified. They act as decoy for miRNAs that are able to target the... (Review)
Review
Two pseudogenes for HMGA1, whose overexpression has a critical role in cancer progression, have been identified. They act as decoy for miRNAs that are able to target the HMGA1 gene then enhancing cell proliferation and migration. Moreover, these pseudogenes contain sequences that are potential target sites for cancer-related miRNAs. Interestingly, HMGA1 pseudogenes are highly expressed in human anaplastic thyroid carcinomas, that is one of the most aggressive tumor in mankind, but almost undetectable in well differentiated thyroid carcinomas.
Topics: Animals; Cell Proliferation; Disease Progression; Gene Expression Regulation, Neoplastic; HMGA Proteins; Humans; MicroRNAs; Neoplasms; Pseudogenes
PubMed: 25483074
DOI: 10.4161/15384101.2014.974440 -
Plant Signaling & Behavior 2019Pseudogenes, nonfunctional genomic sequences derived from functional protein-coding genes, form by duplication or retrotransposition, and loss of gene function by...
Pseudogenes, nonfunctional genomic sequences derived from functional protein-coding genes, form by duplication or retrotransposition, and loss of gene function by disabling mutations. Studies on the evolution and functional aspects of plant pseudogenes are limited, despite their abundance in the plant genome. To date, most researches on pseudogenes focus on mammals. Here, we summarized current knowledge on pseudogenes including the historical and recent progress, analyzes their essential roles in gene regulation in hope of further stimulating researches in plant species for understanding gene regulation and evolution.
Topics: Animals; Evolution, Molecular; Gene Expression Regulation; Genome, Plant; Humans; Mutation; Pseudogenes
PubMed: 31161861
DOI: 10.1080/15592324.2019.1625698 -
Nature Communications Mar 2020Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level....
Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level. Although ubiquitin pseudogenes represent one of the most abundant pseudogene families in many organisms, little is known about their expression and signaling potential. By re-analyzing public RNA-sequencing and proteomics datasets, we here provide evidence for the expression of several ubiquitin pseudogenes including UBB pseudogene 4 (UBBP4), which encodes Ub (Q2K, K33E, Q49K, N60S). The functional consequences of Ub conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that Ub modifies specific proteins including lamins. Knockout of UBBP4 results in slower cell division, and accumulation of lamin A within the nucleolus. Our work suggests that a subset of proteins reported as ubiquitin targets may instead be modified by ubiquitin variants that are the products of wrongly annotated pseudogenes and induce different functional effects.
Topics: CRISPR-Cas Systems; Cell Division; Cell Nucleus; Cloning, Molecular; Datasets as Topic; Gene Knockout Techniques; HEK293 Cells; HeLa Cells; Humans; Lamin Type A; Proteomics; Pseudogenes; RNA-Seq; Ubiquitin; Ubiquitination
PubMed: 32161257
DOI: 10.1038/s41467-020-15090-6 -
Oxidative Medicine and Cellular... 2022Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in...
OBJECTIVE
Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in gliomas. However, its biological function in gliomas remains unclear.
METHODS
In this study, we analyzed clinical data on patients with glioma obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx), and the GEPIA2 databases. We used the R language for the main analysis. Correlations among RPL4P4 expression, pathological characteristics, clinical outcome, and biological function were evaluated. In addition, the correlations of RPL4P4 expression with immune cell infiltration and glioma progression were analyzed. Finally, wound healing, Transwell, and CCK-8 assays were performed to analyze the function of RPL4P4 in glioma cells.
RESULT
We found that RPL4P4 is highly expressed in glioma tissues and is associated with poor prognosis, IDH1 wild type, codeletion of 1p19q, and age. Multivariate analysis and the nomogram model showed that high RPL4P4 expression was an independent risk factor for glioma prognosis and had better prognostic prediction power. Moreover, high RPL4P4 expression correlated with immune cell infiltration, which showed a significant positive association with M2-type macrophages. Finally, RPL4P4 knockdown in glioma cell lines caused decreased glioma cell proliferation, invasion, and migration capacity.
CONCLUSION
Our data suggest that RPL4P4 can function as an independent prognostic predictor of glioma. It also shows that RPL4P4 expression correlates with immune cell infiltration and that targeting RPL4P4 may be a new strategy for the treatment of glioma patients.
Topics: Biomarkers; Brain Neoplasms; Glioma; Humans; Prognosis; Pseudogenes; Ribosomal Proteins
PubMed: 35993018
DOI: 10.1155/2022/7967722 -
PloS One 2014Thousands of pseudogenes exist in the human genome and many are transcribed, but their functional potential remains elusive and understudied. To explore these issues...
Thousands of pseudogenes exist in the human genome and many are transcribed, but their functional potential remains elusive and understudied. To explore these issues systematically, we first developed a computational pipeline to identify transcribed pseudogenes from RNA-Seq data. Applying the pipeline to datasets from 16 distinct normal human tissues identified ∼ 3,000 pseudogenes that could produce non-coding RNAs in a manner of low abundance but high tissue specificity under normal physiological conditions. Cross-tissue comparison revealed that the transcriptional profiles of pseudogenes and their parent genes showed mostly positive correlations, suggesting that pseudogene transcription could have a positive effect on the expression of their parent genes, perhaps by functioning as competing endogenous RNAs (ceRNAs), as previously suggested and demonstrated with the PTEN pseudogene, PTENP1. Our analysis of the ENCODE project data also found many transcriptionally active pseudogenes in the GM12878 and K562 cell lines; moreover, it showed that many human pseudogenes produced small RNAs (sRNAs) and some pseudogene-derived sRNAs, especially those from antisense strands, exhibited evidence of interfering with gene expression. Further integrated analysis of transcriptomics and epigenomics data, however, demonstrated that trimethylation of histone 3 at lysine 9 (H3K9me3), a posttranslational modification typically associated with gene repression and heterochromatin, was enriched at many transcribed pseudogenes in a transcription-level dependent manner in the two cell lines. The H3K9me3 enrichment was more prominent in pseudogenes that produced sRNAs at pseudogene loci and their adjacent regions, an observation further supported by the co-enrichment of SETDB1 (a H3K9 methyltransferase), suggesting that pseudogene sRNAs may have a role in regional chromatin repression. Taken together, our comprehensive and systematic characterization of pseudogene transcription uncovers a complex picture of how pseudogene ncRNAs could influence gene and pseudogene expression, at both epigenetic and post-transcriptional levels.
Topics: Genome, Human; Humans; Pseudogenes; RNA, Untranslated; Transcription, Genetic
PubMed: 24699680
DOI: 10.1371/journal.pone.0093972 -
The International Journal of... Sep 2014A paradigm shift is sweeping modern day molecular biology following the realisation that large amounts of "junk" DNA", thought initially to be evolutionary remnants, may... (Review)
Review
A paradigm shift is sweeping modern day molecular biology following the realisation that large amounts of "junk" DNA", thought initially to be evolutionary remnants, may actually be functional. Several recent studies support a functional role for pseudogene-expressed non-coding RNAs in regulating their protein-coding counterparts. Several hundreds of pseudogenes have been reported as transcribed into RNA in a large variety of tissues and tumours. Most studies have focused on pseudogenes expressed in the sense direction, but some reports suggest that pseudogenes can also be transcribed as antisense RNAs (asRNAs). A few examples of key regulatory genes, such as PTEN and OCT4, have in fact been reported to be under the regulation of pseudogene-expressed asRNAs. Here, we review what are known about pseudogene expressed non-coding RNA mediated gene regulation and their roles in the control of epigenetic states. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.
Topics: Animals; Epigenomics; Gene Expression Regulation; Humans; Pseudogenes; RNA, Antisense; RNA, Long Noncoding; Transcription, Genetic
PubMed: 24842102
DOI: 10.1016/j.biocel.2014.05.008 -
Bioengineered Apr 2022Double homeobox A pseudogene 8 (DUXAP8) is a known tumor promoter in several malignancies. Nonetheless, its function in colon cancer (CC) is indefinite. Herein, we...
Double homeobox A pseudogene 8 (DUXAP8) is a known tumor promoter in several malignancies. Nonetheless, its function in colon cancer (CC) is indefinite. Herein, we explored the significance of DUXAP8 and its underlying mechanism in CC. Our data indicated that DUXAP8 was upregulated in CC, and it was related to advanced stages and lymph node metastases. Based on our Kaplan-Meier survival analysis, elevated DUXAP8 expression resulted in shorter patient overall survival (OS). Conversely, DUXAP8 silencing strongly suppressed cellular proliferation, migration and invasion . Based on our western blot analysis, DUXAP8 deficiency strongly inhibited the epithelial-mesenchymal transition (EMT) . Alternately, DUXAP8 overexpression accelerated cellular proliferation migration and invasion in CC. Finally, silencing DUXAP8 prevented tumorigenesis in a mouse xenograft model . Collectively, our results demonstrated that DUXAP8 regulates the occurrence and advancement of CC, and may serve as a regulatory hub for this disease.
Topics: Animals; Humans; Mice; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Genes, Homeobox; MicroRNAs; Pseudogenes; RNA, Long Noncoding
PubMed: 35287542
DOI: 10.1080/21655979.2022.2053802 -
ELife Apr 2020The partial success of a study to reproduce experiments that linked pseudogenes and cancer proves that understanding RNA networks is more complicated than expected.
The partial success of a study to reproduce experiments that linked pseudogenes and cancer proves that understanding RNA networks is more complicated than expected.
Topics: Biology; Humans; Neoplasms; Pseudogenes; RNA; RNA, Messenger; Reproducibility of Results
PubMed: 32314733
DOI: 10.7554/eLife.56397 -
Nature Communications Jul 2020Pseudogenes are ideal markers of genome remodelling. In turn, the mouse is an ideal platform for studying them, particularly with the recent availability of...
Pseudogenes are ideal markers of genome remodelling. In turn, the mouse is an ideal platform for studying them, particularly with the recent availability of strain-sequencing and transcriptional data. Here, combining both manual curation and automatic pipelines, we present a genome-wide annotation of the pseudogenes in the mouse reference genome and 18 inbred mouse strains (available via the mouse.pseudogene.org resource). We also annotate 165 unitary pseudogenes in mouse, and 303, in human. The overall pseudogene repertoire in mouse is similar to that in human in terms of size, biotype distribution, and family composition (e.g. with GAPDH and ribosomal proteins being the largest families). Notable differences arise in the pseudogene age distribution, with multiple retro-transpositional bursts in mouse evolutionary history and only one in human. Furthermore, in each strain about a fifth of all pseudogenes are unique, reflecting strain-specific evolution. Finally, we find that ~15% of the mouse pseudogenes are transcribed, and that highly transcribed parent genes tend to give rise to many processed pseudogenes.
Topics: Animals; Conserved Sequence; Evolution, Molecular; Gene Ontology; Genome; Humans; Mice, Inbred C57BL; Molecular Sequence Annotation; Pseudogenes; Species Specificity; Transcription, Genetic
PubMed: 32728065
DOI: 10.1038/s41467-020-17157-w