-
Methods in Molecular Biology (Clifton,... 2021Competing endogenous RNA (ceRNA) molecules have emerged as key players in regulating gene expression, increasing the complexity of the range of possible dynamics within...
Competing endogenous RNA (ceRNA) molecules have emerged as key players in regulating gene expression, increasing the complexity of the range of possible dynamics within a cell. The actions of competing RNA typically are sponging behaviors, in a manner that fine-tunes gene expression, but there are particular network structures that may show destabilization due to ceRNA interactions. In this chapter, we discuss how these interactions can be modeled and probed from a mathematical, first-principles perspective.
Topics: Algorithms; Computational Biology; Gene Expression Regulation; Gene Regulatory Networks; MicroRNAs; Models, Theoretical; Pseudogenes; RNA, Long Noncoding; RNA, Messenger; RNA, Untranslated; Regulatory Sequences, Ribonucleic Acid
PubMed: 34165711
DOI: 10.1007/978-1-0716-1503-4_7 -
Current Topics in Microbiology and... 2016Pseudogenes have for long been considered as non-functional relics littering the human genome. Only now, it is becoming apparent that many pseudogenes are transcribed... (Review)
Review
Pseudogenes have for long been considered as non-functional relics littering the human genome. Only now, it is becoming apparent that many pseudogenes are transcribed into long noncoding RNAs, some with proven biological functions. Here, we review the current knowledge of pseudogenes and their widespread functional properties with an emphasis on pseudogenes that have been functionally investigated in greater detail. Pseudogenes are emerging as a novel class of long noncoding RNAs functioning, for example, through microRNA sponging and chromatin remodeling. The examples discussed herein underline that pseudogene-encoded RNAs are important regulatory molecules involved in diseases such as cancer.
Topics: HMGA1a Protein; Humans; Neoplasms; Octamer Transcription Factor-3; PTEN Phosphohydrolase; Pseudogenes; RNA, Long Noncoding
PubMed: 25982975
DOI: 10.1007/82_2015_442 -
Pathology, Research and Practice Jan 2024This review examines and compares the diagnostic and prognostic capabilities of miRNAs and lncRNAs derived from pseudogenes in cancer patients. Additionally, it delves... (Review)
Review
This review examines and compares the diagnostic and prognostic capabilities of miRNAs and lncRNAs derived from pseudogenes in cancer patients. Additionally, it delves into their roles in cancer pathogenesis. Both miRNAs and pseudogene-derived lncRNAs have undergone thorough investigation as remarkably sensitive and specific cancer biomarkers, offering significant potential for cancer detection and monitoring. . Extensive research is essential to gain a complete understanding of the precise roles these non-coding RNAs play in cancer, allowing the development of novel targeted therapies and biomarkers for improved cancer detection and treatment approaches.
Topics: Humans; MicroRNAs; RNA, Long Noncoding; Pseudogenes; Neoplasms; Prognosis; Biomarkers, Tumor
PubMed: 38128189
DOI: 10.1016/j.prp.2023.155014 -
Journal of Experimental & Clinical... Mar 2015Pseudogene was recognized as a potential tumor suppressor or oncogene in varies of diseases, however its roles in glioma have not been investigated. Our study was to...
Pseudogene was recognized as a potential tumor suppressor or oncogene in varies of diseases, however its roles in glioma have not been investigated. Our study was to identify the pseudogene-signature that predicted glioma survival. Using a pseudogene-mining approach, we performed pseudogene expression profiling in 183 glioma samples from the Chinese Glioma Genome Atlas (CGGA) and set it as the training set. We found a six-pseudogene signature correlated with patients' clinical outcome via bioinformatics analyses (P ≤ 0.01), and validated it in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) containing 350 cases. A formula calculating the risk score based on the six-pseudogene signature was introduced and the patients of CGGA set were classified into high-risk group and low-risk group with remarkably different survival (P < 0.001) based on their scores. The prognostic value of the signature was confirmed in the REMBRANDT set. Though the function of these pseudogenes is not clear, the identification of the prognostic pseudogenes indicated the potential roles of pseudogenes in glioma pathogenesis and they may have clinical implications in treating glioma.
Topics: Adult; Aged; Cluster Analysis; Computational Biology; Databases, Nucleic Acid; Female; Gene Expression Profiling; Glioma; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Pseudogenes; ROC Curve; Reproducibility of Results; Transcriptome
PubMed: 25880120
DOI: 10.1186/s13046-015-0137-6 -
World Journal of Surgical Oncology Apr 2021BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA...
BACKGROUND
BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined.
METHODS
Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function.
RESULTS
The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA.
CONCLUSION
Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.
Topics: Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Prognosis; Pseudogenes; Tumor Microenvironment; Urinary Bladder Neoplasms
PubMed: 33888142
DOI: 10.1186/s12957-021-02231-4 -
Molecular Biology and Evolution Mar 2016By definition, pseudogenes are relics of former genes that no longer possess biological functions. Operationally, they are identified based on disruptions of open...
By definition, pseudogenes are relics of former genes that no longer possess biological functions. Operationally, they are identified based on disruptions of open reading frames (ORFs) or presumed losses of promoter activities. Intriguingly, a recent human proteomic study reported peptides encoded by 107 pseudogenes. These peptides may play currently unrecognized physiological roles. Alternatively, they may have resulted from accidental translations of pseudogene transcripts and possess no function. Comparing between human and macaque orthologs, we show that the nonsynonymous to synonymous substitution rate ratio (ω) is significantly smaller for translated pseudogenes than other pseudogenes. In particular, five of 34 translated pseudogenes amenable to evolutionary analysis have ω values significantly lower than 1, indicative of the action of purifying selection. This and other findings demonstrate that some but not all translated pseudogenes have selected functions at the protein level. Hence, neither ORF disruption nor presence of protein product disproves or proves gene functionality at the protein level.
Topics: Amino Acid Sequence; Animals; Base Sequence; Computational Biology; Evolution, Molecular; Genomics; Humans; Molecular Sequence Data; Open Reading Frames; Protein Biosynthesis; Proteome; Pseudogenes; Selection, Genetic; Transcription, Genetic; Transcriptome
PubMed: 26589994
DOI: 10.1093/molbev/msv268 -
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 -
Scientific Reports Apr 2020We have recently identified and characterized two pseudogenes (HMGA1P6 and HMGA1P7) of the HMGA1 gene, which has a critical role in malignant cell transformation and...
We have recently identified and characterized two pseudogenes (HMGA1P6 and HMGA1P7) of the HMGA1 gene, which has a critical role in malignant cell transformation and cancer progression. HMGA1P6 and HMGAP17 act as microRNA decoy for HMGA1 and other cancer-related genes upregulating their protein levels. We have previously shown that they are upregulated in several human carcinomas, and their expression positively correlates with a poor prognosis and an advanced cancer stage. To evaluate in vivo oncogenic activity of HMGA1 pseudogenes, we have generated a HMGA1P7 transgenic mouse line overexpressing this pseudogene. By a mean age of 12 months, about 50% of the transgenic mice developed splenomegaly and accumulation of lymphoid cells in several body compartments. For these mice FACS and immunohistochemical analyses suggested the diagnosis of B-cell lymphoma that was further supported by clonality analyses and RNA expression profile of the pathological tissues of the HMGA1P7 transgenic tissues. Therefore, these results clearly demonstrate the oncogenic activity of HMGA1 pseudogenes in vivo.
Topics: Animals; Flow Cytometry; HMGA1a Protein; Immunohistochemistry; Lymphocytes; Lymphoma, B-Cell; Mice; Mice, Transgenic; NIH 3T3 Cells; Pseudogenes; RNA-Seq
PubMed: 32341372
DOI: 10.1038/s41598-020-62974-0 -
Scientific Reports Mar 2021We identified and characterized the pseudogene complements of five plant species: four dicots (Arabidopsis thaliana, Vitis vinifera, Populus trichocarpa and Phaseolus...
We identified and characterized the pseudogene complements of five plant species: four dicots (Arabidopsis thaliana, Vitis vinifera, Populus trichocarpa and Phaseolus vulgaris) and one monocot (Oryza sativa). Retroposition was considered of modest importance for pseudogene formation in all investigated species except V. vinifera, which showed an unusually high number of retro-pseudogenes in non coding genic regions. By using a pipeline for the classification of sequence duplicates in plant genomes, we compared the relative importance of whole genome, tandem, proximal, transposed and dispersed duplication modes in the pseudo and functional gene complements. Pseudogenes showed higher tendencies than functional genes to genomic dispersion. Dispersed pseudogenes were prevalently fragmented and showed high sequence divergence at flanking regions. On the contrary, those deriving from whole genome duplication were proportionally less than expected based on observations on functional loci and showed higher levels of flanking sequence conservation than dispersed pseudogenes. Pseudogenes deriving from tandem and proximal duplications were in excess compared to functional loci, probably reflecting the high evolutionary rate associated with these duplication modes in plant genomes. These data are compatible with high rates of sequence turnover at neutral sites and double strand break repairs mediated duplication mechanisms.
Topics: Arabidopsis; Conserved Sequence; Evolution, Molecular; Gene Duplication; Gene Expression Regulation, Plant; Genes, Plant; Genetic Loci; Multigene Family; Oryza; Phaseolus; Populus; Pseudogenes; Vitis
PubMed: 33674668
DOI: 10.1038/s41598-021-84778-6 -
Scientific Reports May 2023Accumulating evidence shows that pseudogenes can function as microRNAs (miRNAs) sponges and regulate gene expression. Mining potential interactions between pseudogenes...
Accumulating evidence shows that pseudogenes can function as microRNAs (miRNAs) sponges and regulate gene expression. Mining potential interactions between pseudogenes and miRNAs will facilitate the clinical diagnosis and treatment of complex diseases. However, identifying their interactions through biological experiments is time-consuming and labor intensive. In this study, an ensemble learning framework with similarity kernel fusion is proposed to predict pseudogene-miRNA associations, named ELPMA. First, four pseudogene similarity profiles and five miRNA similarity profiles are measured based on the biological and topology properties. Subsequently, similarity kernel fusion method is used to integrate the similarity profiles. Then, the feature representation for pseudogenes and miRNAs is obtained by combining the pseudogene-pseudogene similarities, miRNA-miRNA similarities. Lastly, individual learners are performed on each training subset, and the soft voting is used to yield final decision based on the prediction results of individual learners. The k-fold cross validation is implemented to evaluate the prediction performance of ELPMA method. Besides, case studies are conducted on three investigated pseudogenes to validate the predict performance of ELPMA method for predicting pseudogene-miRNA interactions. Therefore, all experiment results show that ELPMA model is a feasible and effective tool to predict interactions between pseudogenes and miRNAs.
Topics: MicroRNAs; Pseudogenes; Machine Learning; Computational Biology; Algorithms
PubMed: 37258695
DOI: 10.1038/s41598-023-36054-y