-
Reports of Practical Oncology and... 2023Skin melanoma is one of the deadliest types of skin cancer and develops from melanocytes. The genetic aberrations in protein-coding genes are well characterized, but...
BACKGROUND
Skin melanoma is one of the deadliest types of skin cancer and develops from melanocytes. The genetic aberrations in protein-coding genes are well characterized, but little is known about changes in non-coding RNAs (ncRNAs) such as pseudogenes. Ribosomal protein pseudogenes (RPPs) have been described as the largest group of pseudogenes which are dispersed in the human genome.
MATERIALS AND METHIDS
We looked deeply at the role of one of them, ribosomal protein L23a pseudogene 53 (), and its potential diagnostic use. The expression level of was profiled in melanoma cell lines using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and analyzed based on the Cancer Genome Atlas (TCGA) data depending on status and clinicopathological parameters. Cellular phenotype, which was associated with levels, was described based on the REACTOME pathway browser, Gene Set Enrichment Analysis (GSEA) analysis as well as Immune and ESTIMATE Scores.
RESULTS
We indicted changes in level depending on a cell line, and based on analysis of TCGA samples demonstrated significant differences in expression between primary and metastatic melanoma, as well as correlation between and overall survival. No differences depending on status were observed. is associated with several signaling pathways and cellular processes.
CONCLUSIONS
This study showed that patients with higher expression of displayed changed infiltration of lymphocytes, macrophages, and neutrophils compared to groups with lower expression of . pseudogene is differently expressed in melanoma compared with normal tissue and its expression is associated with cellular proliferation. Thus, it may be considered as an indicator of patients' survival and a marker for the immune profile assessment.
PubMed: 37456695
DOI: 10.5603/RPOR.a2023.0030 -
PloS One 2021Several molecular phylogenetic studies of the mistletoe family Loranthaceae have been published such that now the general pattern of relationships among the genera and...
Several molecular phylogenetic studies of the mistletoe family Loranthaceae have been published such that now the general pattern of relationships among the genera and their biogeographic histories are understood. Less is known about species relationships in the larger (> 10 species) genera. This study examines the taxonomically difficult genus Taxillus composed of 35-40 Asian species. The goal was to explore the genetic diversity present in Taxillus plastomes, locate genetically variable hotspots, and test these for their utility as potential DNA barcodes. Using genome skimming, complete plastomes, as well as nuclear and mitochondrial rDNA sequences, were newly generated for eight species. The plastome sequences were used in conjunction with seven publicly available Taxillus sequences and three sequences of Scurrula, a close generic relative. The Taxillus plastomes ranged from 121 to 123 kbp and encoded 90-93 plastid genes. In addition to all of the NADH dehydrogenase complex genes, four ribosomal genes, infA and four intron-containing tRNA genes were lost or pseudogenized in all of the Taxillus and Scurrula plastomes. The topologies of the plastome, mitochondrial rDNA and nuclear rDNA trees were generally congruent, though with discordance at the position of T. chinensis. Several variable regions in the plastomes were identified that have sufficient numbers of parsimony informative sites as to recover the major clades seen in the complete plastome tree. Instead of generating complete plastome sequences, our study showed that accD alone or the concatenation of accD and rbcL can be used in future studies to facilitate identification of Taxillus samples and to generate a molecular phylogeny with robust sampling within the genus.
Topics: DNA, Ribosomal; Evolution, Molecular; Genome, Plastid; Loranthaceae; Mitochondria; NADH Dehydrogenase; Phylogeny; Plastids; RNA, Transfer; Ribosomal Proteins
PubMed: 34407123
DOI: 10.1371/journal.pone.0256345 -
Epigenetics Dec 2023Pancreatic adenocarcinoma is one of the leading lethal human cancer types and is notorious for its poor prognosis. A series of bioinformatic analyses and experimental...
Pancreatic adenocarcinoma is one of the leading lethal human cancer types and is notorious for its poor prognosis. A series of bioinformatic analyses and experimental validations were employed to explore the role and mechanism of pseudogene-derived RNAs in pancreatic adenocarcinoma. Consequently, a total of 13 upregulated and 7 downregulated pseudogene-derived RNAs in pancreatic adenocarcinoma were identified. Survival analysis revealed a statistically predictive role of AK4P1 for unfavourable prognosis of patients with pancreatic adenocarcinoma. Subcellular location analysis indicated that AK4P1 was mainly located in cytoplasm, in which AK4P1 might competitively bind to tumour suppressive miR-375 in pancreatic adenocarcinoma. Further analysis showed that SP1 was a potential downstream target gene of miR-375 in pancreatic adenocarcinoma. Intriguingly, expression determination validated that SP1 could positively regulate AK4P1 levels in pancreatic adenocarcinoma. Finally, AK4P1 might also exert its effects by interacting with oncogenic parental gene AK4 in pancreatic adenocarcinoma. Conclusively, the present study elucidated a key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma.
Topics: Humans; Adenocarcinoma; Cell Line, Tumor; Cell Proliferation; DNA Methylation; Gene Expression Regulation, Neoplastic; MicroRNAs; Pancreatic Neoplasms; Prognosis; Sp1 Transcription Factor; Adenylate Kinase
PubMed: 36476264
DOI: 10.1080/15592294.2022.2148433 -
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 -
Science Advances Oct 2021Pseudogenes, noncoding homologs of protein-coding genes, once considered nonfunctional evolutionary relics, have recently been linked to patient prognoses and cancer...
Pseudogenes, noncoding homologs of protein-coding genes, once considered nonfunctional evolutionary relics, have recently been linked to patient prognoses and cancer subtypes. Despite this potential clinical importance, only a handful of >12,000 pseudogenes in humans have been characterized in cancers to date. Here, we describe a previously unrecognized role for pseudogenes as potent epigenetic regulators that can demethylate and activate oncogenes. We focused on , a known oncogene in hepatocellular carcinoma (HCC) with eight pseudogenes. Using a locus-specific demethylating technology, we identified the critical CpG region for SALL4 expression. We demonstrated that pseudogene 5 hypomethylates this region through interaction with DNMT1, resulting in SALL4 up-regulation. Intriguingly, pseudogene 5 is significantly up-regulated in a hepatitis B virus model before SALL4 induction, and both are increased in patients with HBV-HCC. Our results suggest that pseudogene-mediated demethylation represents a novel mechanism of oncogene activation in cancer.
PubMed: 34597139
DOI: 10.1126/sciadv.abg1695 -
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 -
Cells Mar 2020The nematode possesses a unique (with various isoforms) FOXO transcription factor DAF-16, which is notorious for its role in aging and its regulation by the... (Review)
Review
The nematode possesses a unique (with various isoforms) FOXO transcription factor DAF-16, which is notorious for its role in aging and its regulation by the insulin-PI3K-AKT pathway. In humans, five genes (including a protein-coding pseudogene) encode for FOXO transcription factors that are targeted by the PI3K-AKT axis, such as in . This common regulation and highly conserved DNA-binding domain are the pillars of this family. In this review, I will discuss the possible meaning of possessing a group of very similar proteins and how it can generate additional functionality to more complex organisms. I frame this discussion in relation to the much larger super family of Forkhead proteins to which they belong. FOXO members are very often co-expressed in the same cell type. The overlap of function and expression creates a certain redundancy that might be a safeguard against the accidental loss of FOXO function, which could otherwise lead to disease, particularly, cancer. This is one of the points that will be examined in this "family affair" report.
Topics: Animals; Caenorhabditis elegans; Evolution, Molecular; Forkhead Transcription Factors; Humans; Multigene Family
PubMed: 32214027
DOI: 10.3390/cells9030787 -
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