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Emerging Infectious Diseases Sep 2023Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild...
Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.
Topics: Animals; Humans; Goats; Prevalence; Phylogeny; Genomics; Anaplasma; China
PubMed: 37610104
DOI: 10.3201/eid2909.230131 -
International Journal of Oncology Mar 2024Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain...
Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non‑coding RNAs, reverse transcription‑quantitative PCR, fluorescence hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for studies. and studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor‑promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR‑6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR‑6072/UBD network may serve as a potential therapeutic strategy for glioma patients.
Topics: Animals; Humans; Mice; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioma; In Situ Hybridization, Fluorescence; MicroRNAs; Pseudogenes; RNA, Long Noncoding
PubMed: 38275102
DOI: 10.3892/ijo.2024.5617 -
Cancers Oct 2023The phosphatase and tensin homolog deleted on chromosome 10 () is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental... (Review)
Review
The phosphatase and tensin homolog deleted on chromosome 10 () is a well characterised tumour suppressor, playing a critical role in the maintenance of fundamental cellular processes including cell proliferation, migration, metabolism, and survival. Subtle decreases in cellular levels of PTEN result in the development and progression of cancer, hence there is tight regulation of the expression, activity, and cellular half-life of PTEN at the transcriptional, post-transcriptional, and post-translational levels. , the processed pseudogene of , is an important transcriptional and post-transcriptional regulator of expression produces sense and antisense transcripts modulating expression, in conjunction with miRNAs. Due to the high sequence similarity between and the sense transcript, the transcripts possess common miRNA binding sites with the potential for to compete for the binding, or 'sponging', of miRNAs that would otherwise target the transcript. therefore acts as a competitive endogenous RNA (ceRNA), competing with for the binding of specific miRNAs to alter the abundance of PTEN. Transcription from the antisense strand produces two functionally independent isoforms (- and ), which can regulate transcription. In this review, we provide an overview of the post-transcriptional regulation of through interaction with its pseudogene, the cellular miRNA milieu and operation of the ceRNA network. Furthermore, its importance in maintaining cellular integrity and how disruption of this -miRNA- axis may lead to cancer but also provide novel therapeutic opportunities, is discussed. Precision targeting of -miRNA mediated regulation of may present as a viable alternative therapy.
PubMed: 37894321
DOI: 10.3390/cancers15204954 -
Frontiers in Genetics 2024The clinical application of technological progress in the identification of DNA alterations has always led to improvements of diagnostic yields in genetic medicine. At... (Review)
Review
The clinical application of technological progress in the identification of DNA alterations has always led to improvements of diagnostic yields in genetic medicine. At chromosome side, from cytogenetic techniques evaluating number and gross structural defects to genomic microarrays detecting cryptic copy number variants, and at molecular level, from Sanger method studying the nucleotide sequence of single genes to the high-throughput next-generation sequencing (NGS) technologies, resolution and sensitivity progressively increased expanding considerably the range of detectable DNA anomalies and alongside of Mendelian disorders with known genetic causes. However, particular genomic regions (i.e., repetitive and GC-rich sequences) are inefficiently analyzed by standard genetic tests, still relying on laborious, time-consuming and low-sensitive approaches (i.e., southern-blot for repeat expansion or long-PCR for genes with highly homologous pseudogenes), accounting for at least part of the patients with undiagnosed genetic disorders. Third generation sequencing, generating long reads with improved mappability, is more suitable for the detection of structural alterations and defects in hardly accessible genomic regions. Although recently implemented and not yet clinically available, long read sequencing (LRS) technologies have already shown their potential in genetic medicine research that might greatly impact on diagnostic yield and reporting times, through their translation to clinical settings. The main investigated LRS application concerns the identification of structural variants and repeat expansions, probably because techniques for their detection have not evolved as rapidly as those dedicated to single nucleotide variants (SNV) identification: gold standard analyses are karyotyping and microarrays for balanced and unbalanced chromosome rearrangements, respectively, and southern blot and repeat-primed PCR for the amplification and sizing of expanded alleles, impaired by limited resolution and sensitivity that have not been significantly improved by the advent of NGS. Nevertheless, more recently, with the increased accuracy provided by the latest product releases, LRS has been tested also for SNV detection, especially in genes with highly homologous pseudogenes and for haplotype reconstruction to assess the parental origin of alleles with pathogenic variants. We provide a review of relevant recent scientific papers exploring LRS potential in the diagnosis of genetic diseases and its potential future applications in routine genetic testing.
PubMed: 38510277
DOI: 10.3389/fgene.2024.1374860 -
Alternative Therapies in Health and... Oct 2023Lung squamous cell carcinoma (LUSC) accounts for 30% of non-small-cell lung cancers (NSCLC), and an effective pharmacological treatment for LUSC isn't yet available. The...
CONTEXT
Lung squamous cell carcinoma (LUSC) accounts for 30% of non-small-cell lung cancers (NSCLC), and an effective pharmacological treatment for LUSC isn't yet available. The Xihuang Pill is a potent Chinese medicinal preparation widely prescribed for the management of LUSC.
OBJECTIVE
The study intended to use the network-pharmacology method to ascertain the effective active ingredients, targets of action, and cellular-signal transduction involved in the prevention and treatment of LUSC when using the Xihuang Pill and to identify the mechanism of action of the pills against LUSC, to provide a more adequate scientific basis for subsequent studies.
DESIGN
The research team performed a genetic study.
SETTING
The study took place at Shanghai.
OUTCOME MEASURES
The research team: (1) created the feature sets, for both the LUSC and normal features, using the Cancer Genome Atlas' (TCGA's) LUSC dataset; (2) performed a weighted correlation network analysis (WGCNA) of the differentially expressed genes (DEGs) using the R package WGCNA; (3) searched for the chemical components of the Xihuang Pill using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and the Herb Group Identification Platform, and (4) selected the novel the Matthews correlation coefficient (MCC) algorithm to screen the hub genes.
RESULTS
The study found 8713 DEGs between the LUSC and normal groups. The top ten, important, downregulated genes included: (1) advanced glycosylation end product (AGER), (2) chitinase, acidic pseudogene 2 (CHIAP2), (3) CD300 molecule like family member G (CD300LG), (4) solute carrier family 6 member 4 (SLC6A4), (5) carboxypeptidase B2 (CPB2), (6) claudin 18 (CLDN18), (7) gamma-glutamyltransferase light chain 1 (GGTLC1), (8) gastrokine 2 (GKN2), (9) progastricsin (PGC), and (10) pulmonary surfactant-associated protein C (SFTPC). The top 10 upregulated genes included: (1) cancer susceptibility 9 (CASC9), (2) homeobox C13 (HOXC13), (3) keratin 6a (KRT6A), (4) desmoglein 3 (DSG3), (5) keratin 16 (KRT16), (6) forkhead box E1 (FOXE1), (7) preferentially expressed antigen in melanoma (PRAME), (8) calmodulin-like protein 3 (CALML3), (9) KRT68, and (10) aldo-keto reductase family 1 member B10 (AKR1B10). The study found 41 active ingredients and 843 targets for the Xihuang Pill. The PPI network included 10 hub genes, including cyclin dependent kinase 1 (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), polo-like kinase 1 (PLK1), aurora kinase B (AURKB), baculoviral IAP repeat containing 5 (BIRC5), cyclin A2 (CCNA2), aurora kinase A (AURKA), centrosome-associated protein E (CENPE), and threonine tyrosine kinase (TTK), which were the principal target genes at the core of the gene-pathway network for the drug compound to central-target relationship. The enrichment analyses used the overlapping genes and the 10 hub genes and found 390 biological processes (BPs), 25 molecular functions (MFs), 43 cellular components (CCs), and 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The main enrichment occurred in the regulation of protein serine-threonine kinase activity, mitotic nuclear division, progesterone-mediated oocyte maturation, and the cell cycle.
CONCLUSIONS
The study found the targets and relevant pathways of the hub genes of Xihuang Pill using biological analysis and molecular docking and demonstrated the interactions of critical chemical compounds with the hub's targeted genes were. More research is necessary to further determine whether the Xihuang Pill can improve LUSC patients' survival rate by regulation of those genes.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Network Pharmacology; Molecular Docking Simulation; Lung Neoplasms; China; Carcinoma, Squamous Cell; Lung; Claudins; Antigens, Neoplasm; Serotonin Plasma Membrane Transport Proteins
PubMed: 37442189
DOI: No ID Found -
EMBO Reports Mar 2024Embryonic genome activation (EGA) occurs during preimplantation development and is characterized by the initiation of de novo transcription from the embryonic genome....
Embryonic genome activation (EGA) occurs during preimplantation development and is characterized by the initiation of de novo transcription from the embryonic genome. Despite its importance, the regulation of EGA and the transcription factors involved in this process are poorly understood. Paired-like homeobox (PRDL) family proteins are implicated as potential transcriptional regulators of EGA, yet the PRDL-mediated gene regulatory networks remain uncharacterized. To investigate the function of PRDL proteins, we are identifying the molecular interactions and the functions of a subset family of the Eutherian Totipotent Cell Homeobox (ETCHbox) proteins, seven PRDL family proteins and six other transcription factors (TFs), all suggested to participate in transcriptional regulation during preimplantation. Using mass spectrometry-based interactomics methods, AP-MS and proximity-dependent biotin labeling, and chromatin immunoprecipitation sequencing we derive the comprehensive regulatory networks of these preimplantation TFs. By these interactomics tools we identify more than a thousand high-confidence interactions for the 21 studied bait proteins with more than 300 interacting proteins. We also establish that TPRX2, currently assigned as pseudogene, is a transcriptional activator.
Topics: Humans; Transcription Factors; Homeodomain Proteins; Genes, Homeobox; Genome
PubMed: 38297188
DOI: 10.1038/s44319-024-00074-0 -
Pharmacological Reviews Feb 2024In humans, there are two arylamine N-acetyltransferase genes that encode functional enzymes ( and ) as well as one pseudogene, all of which are located together on... (Review)
Review
In humans, there are two arylamine N-acetyltransferase genes that encode functional enzymes ( and ) as well as one pseudogene, all of which are located together on chromosome 8. Although they were first identified by their role in the acetylation of drugs and other xenobiotics, recent studies have shown strong associations for both enzymes in a variety of diseases, including cancer, cardiovascular disease, and diabetes. There is growing evidence that this association may be causal. Consistently, NAT1 and NAT2 are shown to be required for healthy mitochondria. This review discusses the current literature on the role of both NAT1 and NAT2 in mitochondrial bioenergetics. It will attempt to relate our understanding of the evolution of the two genes with biologic function and then present evidence that several major metabolic diseases are influenced by NAT1 and NAT2. Finally, it will discuss current and future approaches to inhibit or enhance NAT1 and NAT2 activity/expression using small-molecule drugs. SIGNIFICANCE STATEMENT: The arylamine N-acetyltransferases (NATs) NAT1 and NAT2 share common features in their associations with mitochondrial bioenergetics. This review discusses mitochondrial function as it relates to health and disease, and the importance of NAT in mitochondrial function and dysfunction. It also compares NAT1 and NAT2 to highlight their functional similarities and differences. Both NAT1 and NAT2 are potential drug targets for diseases where mitochondrial dysfunction is a hallmark of onset and progression.
Topics: Humans; Arylamine N-Acetyltransferase; Acetyltransferases; Substrate Specificity; Metabolic Diseases; Mitochondrial Diseases
PubMed: 38351074
DOI: 10.1124/pharmrev.123.000835 -
Plant Physiology Sep 2023Sex chromosomes have evolved independently in many different plant lineages. Here, we describe reference genomes for spinach (Spinacia oleracea) X and Y haplotypes by...
Sex chromosomes have evolved independently in many different plant lineages. Here, we describe reference genomes for spinach (Spinacia oleracea) X and Y haplotypes by sequencing homozygous XX females and YY males. The long arm of 185-Mb chromosome 4 carries a 13-Mb X-linked region (XLR) and 24.1-Mb Y-linked region (YLR), of which 10 Mb is Y specific. We describe evidence that this reflects insertions of autosomal sequences creating a "Y duplication region" or "YDR" whose presence probably directly reduces genetic recombination in the immediately flanking regions, although both the X and Y sex-linked regions are within a large pericentromeric region of chromosome 4 that recombines rarely in meiosis of both sexes. Sequence divergence estimates using synonymous sites indicate that YDR genes started diverging from their likely autosomal progenitors about 3 MYA, around the time when the flanking YLR stopped recombining with the XLR. These flanking regions have a higher density of repetitive sequences in the YY than the XX assembly and include slightly more pseudogenes compared with the XLR, and the YLR has lost about 11% of the ancestral genes, suggesting some degeneration. Insertion of a male-determining factor would have caused Y linkage across the entire pericentromeric region, creating physically small, highly recombining, terminal pseudoautosomal regions. These findings provide a broader understanding of the origin of sex chromosomes in spinach.
Topics: Spinacia oleracea; Repetitive Sequences, Nucleic Acid; Sex Chromosomes; Evolution, Molecular
PubMed: 37403642
DOI: 10.1093/plphys/kiad389 -
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 -
Experimental Neurology Sep 2023Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Vasculogenic mimicry (VM) is a hematological system composed of tumor cells that...
Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Vasculogenic mimicry (VM) is a hematological system composed of tumor cells that exert blood perfusion without relying on vascular endothelial cells. The current poor results of anti-vascular therapy for clinical GBM are associated with the presence of VM; therefore, it is important to investigate VM formation in GBM. Our results demonstrate that STK24P1 encodes P1-121aa with a kinase structural domain, and in vitro kinase assays demonstrated that P1-121aa mediates modification of ELF2 phosphorylation. ChIP and dual luciferase reporter gene assays demonstrated that the transcription factor ELF2 binds to VE-cadherin and the VEGFR2 promoter region, thereby promoting VM formation in glioma cells. P1-121aa, encoded by the pseudogene STK24P1, phosphorylates ELF2 at S107, increasing the stability of the ELF2 protein. ELF2 promotes VEGFR2 and VE-cadherin expression at the transcriptional level, which in turn promotes VM in GBM. This study demonstrates the important roles of STK24P1, P1-121aa, and ELF2 in regulating VM in GBM, which could provide potential targets for GBM treatment.
Topics: Humans; Glioblastoma; Phosphorylation; Endothelial Cells; Neovascularization, Pathologic; Peptides; Cell Line, Tumor; Transcription Factors
PubMed: 37406957
DOI: 10.1016/j.expneurol.2023.114477