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International Journal of Molecular... Nov 2019Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, gene is in linkage disequilibrium with gene... (Review)
Review
Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, gene is in linkage disequilibrium with gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and exchanges between lipoprotein classes. These interactions occur via amphipathic helix motifs, as demonstrated by biophysical studies on the wild-type polypeptide and representative mutants. Apolipoprotein C1 acts on lipoprotein receptors by inhibiting binding mediated by apolipoprotein E, and modulating the activities of several enzymes. Thus, apoC1 downregulates lipoprotein lipase, hepatic lipase, phospholipase A2, cholesterylester transfer protein, and activates lecithin-cholesterol acyl transferase. By controlling the plasma levels of lipids, apoC1 relates directly to cardiovascular physiology, but its activity extends beyond, to inflammation and immunity, sepsis, diabetes, cancer, viral infectivity, and-not last-to cognition. Such correlations were established based on studies using transgenic mice, associated in the recent years with GWAS, transcriptomic and proteomic analyses. The presence of a duplicate gene, pseudogene , stimulated evolutionary studies and more recently, the regulatory properties of the corresponding non-coding RNA are steadily emerging. Nonetheless, this prototypical apolipoprotein is still underexplored and deserves further research for understanding its physiology and exploiting its therapeutic potential.
Topics: Amino Acid Motifs; Apolipoprotein C-I; Apolipoproteins E; Chromosome Mapping; Gene Expression Regulation; Humans; Lipid Metabolism; Lipoproteins, HDL; Lipoproteins, VLDL; Protein Binding; Pseudogenes; Receptors, Lipoprotein
PubMed: 31779116
DOI: 10.3390/ijms20235939 -
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 -
Frontiers in Immunology 2019Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the... (Review)
Review
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the pathologic conditions associated with inflammation. Long non-coding RNAs (lncRNAs) are untranslated functional RNA molecules. The lncRNAs are involved in the control of a wide variety of cellular processes and are dysregulated in different diseases. They can participate in the modulation of immune function and activity of inflammatory cells, including MDSCs. This mini review focuses on the emerging role of lncRNAs in MDSC activity. We summarize how lncRNAs modulate the generation, recruitment, and immunosuppressive functions of MDSCs and the underlying mechanisms.
Topics: Animals; CCAAT-Enhancer-Binding Protein-beta; Cell Lineage; Epigenesis, Genetic; Forecasting; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Inflammation; Mice; Myeloid-Derived Suppressor Cells; Neoplasms; Nitric Oxide; Pseudogenes; RNA, Long Noncoding; RNA, Neoplasm; Reactive Oxygen Species; Tumor Escape; Tumor Microenvironment
PubMed: 31404149
DOI: 10.3389/fimmu.2019.01734 -
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 -
Hereditas Nov 2022Gastric cancer is one of the most common and deadly types of cancer. The molecular mechanism of gastric cancer progression remains unclear.
OBJECTIVE
Gastric cancer is one of the most common and deadly types of cancer. The molecular mechanism of gastric cancer progression remains unclear.
MATERIALS AND METHODS
Four hub genes were identified through GEO and TCGA database screening and analysis. Prognostic analysis revealed that COL5A2 was the most likely to affect the prognosis of gastric cancer among the four hub genes. The relationships between COL5A2 and clinical variables and immune cell infiltration were analyzed. Then, COL5A2 was analyzed for single-gene differences and related functional enrichment. Using the starBase database for prediction and analysis, miRNAs and pseudogenes/lncRNAs that might combine with COL5A2 were identified; thus, the ceRNA network was constructed. Finally, the network was verified by Cox analysis and qPCR, and a nomogram was constructed.
RESULTS
First, we found that COL5A2, COL12A1, BGN and THBS2 were highly expressed in gastric cancer. COL5A2 had statistical significance in overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) analysis. Immune infiltration analysis suggested that COL5A2 might influence the changes in the tumor immune microenvironment. The StarBase database was used to predict that 3 pseudogenes and 7 lncRNAs might inhibit the hsa-miR-200b-3p-COL5A2 axis in gastric cancer. The pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 ceRNA network was identified and verified using Cox regression analysis and PCR. Finally, we constructed a nomogram.
CONCLUSIONS
We elucidated the regulatory role of the pseudogenes/lncRNA-hsa-miR-200b-3p-COL5A2 network in gastric cancer progression and constructed a nomogram. These studies may provide effective treatments and potential prognostic biomarkers for gastric cancer.
Topics: Humans; RNA, Long Noncoding; Pseudogenes; Stomach Neoplasms; Prognosis; MicroRNAs; Biomarkers; Tumor Microenvironment
PubMed: 36447214
DOI: 10.1186/s41065-022-00257-6 -
Molecular Biology and Evolution Jun 2020Mobile genetic elements (MGEs) often encode integrases which catalyze the site-specific insertion of their genetic information into the host genome and the reverse...
Mobile genetic elements (MGEs) often encode integrases which catalyze the site-specific insertion of their genetic information into the host genome and the reverse reaction of excision. Hyperthermophilic archaea harbor integrases belonging to the SSV-family which carry the MGE recombination site within their open reading frame. Upon integration into the host genome, SSV integrases disrupt their own gene into two inactive pseudogenes and are termed suicidal for this reason. The evolutionary maintenance of suicidal integrases, concurring with the high prevalence and multiples recruitments of these recombinases by archaeal MGEs, is highly paradoxical. To elucidate this phenomenon, we analyzed the wide phylogenomic distribution of a prominent class of suicidal integrases which revealed a highly variable integration site specificity. Our results highlighted the remarkable hybrid nature of these enzymes encoded from the assembly of inactive pseudogenes of different origins. The characterization of the biological properties of one of these integrases, IntpT26-2 showed that this enzyme was active over a wide range of temperatures up to 99 °C and displayed a less-stringent site specificity requirement than comparable integrases. These observations concurred in explaining the pervasiveness of these suicidal integrases in the most hyperthermophilic organisms. The biochemical and phylogenomic data presented here revealed a target site switching system operating on highly thermostable integrases and suggested a new model for split gene reconstitution. By generating fast-evolving pseudogenes at high frequency, suicidal integrases constitute a powerful model to approach the molecular mechanisms involved in the generation of active genes variants by the recombination of proto-genes.
Topics: Evolution, Molecular; Hydrothermal Vents; Integrases; Interspersed Repetitive Sequences; Pseudogenes; Thermococcus
PubMed: 32068866
DOI: 10.1093/molbev/msaa041