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Cell Biology International Jan 2023Among malignant tumors, lung adenocarcinoma (LUAD) is the leading cause of death worldwide. This study explored the diagnostic, prognostic value, and preliminary...
Among malignant tumors, lung adenocarcinoma (LUAD) is the leading cause of death worldwide. This study explored the diagnostic, prognostic value, and preliminary functional verification of sialic acid binding Ig like lectin 17, pseudogene (SIGLEC17P) in LUAD. Prognostic lncRNAs for LUAD were identified by The Cancer Genome Atlas and quantitative real-time PCR (qRT-PCR) was used to detect the expression of SIGLEC17P in LUAD and paracarcinoma tissues. Subsequently, lentiviral vectors were used to overexpress SIGLEC17P in A549 and H1299 cells. The effects of SIGLEC17P overexpression on the proliferation, migration, and invasiveness of LUAD cells (A549 and H1299) were evaluated by Cell Counting Kit-8, wound healing, and transwell migration assays, respectively. Bioinformatics analyses were performed to reveal the potential pathways in which SIGLEC17P is involved in LUAD. qRT-PCR results revealed low SIGLEC17P expression in LUAD tissues and a significant association with the N stage, T stage, and tumor node metastasis stage. Furthermore, the receiver operating characteristic curve demonstrated a reliable diagnostic value. The proliferation, migration, and invasion of LUAD cells were inhibited by overexpression of SIGLEC17P. Bioinformatics analyses suggested that SIGLEC17P might exert antioncogenic effects in LUAD through the mir-20-3p/ADH1B or mir-4476-5p/DPYSL axis. In summary, our results revealed that SIGLEC17P acts as a prognostic biomarker, independent prognostic factor, and potential therapeutic target for patients with LUAD.
Topics: Humans; Adenocarcinoma; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Lung Neoplasms; MicroRNAs; Prognosis; Pseudogenes
PubMed: 36183365
DOI: 10.1002/cbin.11919 -
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 -
Journal of Cellular Physiology Oct 2020The incidence and mortality rate of hepatocellular carcinoma (HCC) nowadays is still at high levels. The regulatory roles of pseudogene in cancers have been gradually...
The incidence and mortality rate of hepatocellular carcinoma (HCC) nowadays is still at high levels. The regulatory roles of pseudogene in cancers have been gradually recognized in recent years. However, comprehensive investigation of abnormally expressed pseudogene and related mechanisms in HCC remains lacking. GSE124535 dataset was used to identify differentially expressed pseudogenes in HCC tissues compared with normal tissues. Prognostic value of these differentially expressed pseudogenes was analyzed at GEPIA. StarBase used to analyze microRNAs (miRNAs) can bind with pseudogene, while the targets for these miRNAs were analyzed at miRTarBase. Protein-protein interaction (PPI) network was then established for miRNA targets, after that hub genes were selected. Expression correlation of pseudogene and hub genes was analyzed at StarBase. In total, 16 upregulated and 17 downregulated pseudogenes were identified. Pseudogene HSPB1P1 was identified abnormally expressed in 20 types of human cancers and could be used as an indicator for poorer overall survival of patients with HCC. Functional analyses showed that HSPB1P1 was strongly correlated with signaling pathways related to cancer progression. Further studied revealed that HSPB1P1 could direct regulate the EZH2 expression in HCC. In summary, our study indicated that HSPB1P1 was a predictor for poorer overall survival of patients with HCC and may be potential therapeutic target against HCC.
Topics: Carcinoma, Hepatocellular; Down-Regulation; Enhancer of Zeste Homolog 2 Protein; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Heat-Shock Proteins; Humans; Liver Neoplasms; MicroRNAs; Prognosis; Protein Interaction Maps; Pseudogenes; Signal Transduction; Up-Regulation
PubMed: 31985034
DOI: 10.1002/jcp.29459 -
Biochimica Et Biophysica Acta Jan 2015B chromosomes are supernumerary dispensable parts of the karyotype which appear in some individuals of some populations in some species. Often, they have been considered... (Review)
Review
BACKGROUND
B chromosomes are supernumerary dispensable parts of the karyotype which appear in some individuals of some populations in some species. Often, they have been considered as 'junk DNA' or genomic parasites without functional genes.
SCOPE OF REVIEW
Due to recent advances in sequencing technologies, it became possible to investigate their DNA composition, transcriptional activity and effects on the host transcriptome profile in detail. Here, we review the most recent findings regarding the gene content of B chromosomes and their transcriptional activities and discuss these findings in the context of comparable biological phenomena, like sex chromosomes, aneuploidy and pseudogenes.
MAJOR CONCLUSIONS
Recent data suggest that B chromosomes carry transcriptionally active genic sequences which could affect the transcriptome profile of their host genome.
GENERAL SIGNIFICANCE
These findings are gradually changing our view that B chromosomes are solely genetically inert selfish elements without any functional genes. This at one side could partly explain the deleterious effects which are associated with their presence. On the other hand it makes B chromosome a nice model for studying regulatory mechanisms of duplicated genes and their evolutionary consequences.
Topics: Animals; Chromosomes; DNA, Intergenic; Eukaryota; Evolution, Molecular; Gene Expression Regulation; Genome; Humans; In Situ Hybridization, Fluorescence; Pseudogenes; Transcription, Genetic
PubMed: 25481283
DOI: 10.1016/j.bbagrm.2014.11.007 -
Methods in Molecular Biology (Clifton,... 2021PTENP1 is a processed pseudogene of the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). It functions posttranscriptionally to regulate...
PTENP1 is a processed pseudogene of the tumour suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). It functions posttranscriptionally to regulate PTEN by acting as a sponge for microRNAs that target PTEN. PTENP1 therefore functions as a competitive endogenous RNA (ceRNA), competing with PTEN for binding of microRNAs (miRNA) and thereby modulating PTEN cellular abundance. Studies of the overexpression of PTENP1 all confirm its oncosuppressive function to be mediated through the suppression of cell proliferation, induction of apoptosis, and inhibition of cell migration and invasion of cancer cells of differing types. These oncosuppressive functions are a direct consequence of miRNA binding by PTENP1 and the subsequent liberation of PTEN from miRNA induced suppression. In this chapter, we will focus initially on the description of a high efficiency transient transfection method to introduce and overexpress PTENP1 in the cell type of interest, followed by accurate methodologies to measure transfection efficiency by flow cytometry. We will then continue to describe two methods to analyze cell proliferation, namely the CCK-8 assay and Click-iT EdU assay. Due to commonalities in the manifestation of the oncosuppressive effects of PTENP1, mediated through its role as a ceRNA, the methods presented in this chapter will have wide applicability to a variety of different cell types.
Topics: 3' Untranslated Regions; Animals; Binding, Competitive; Cell Count; Cell Division; Cell Line, Tumor; Cloning, Molecular; Colorimetry; DNA Replication; Flow Cytometry; Fluorescent Dyes; Humans; MicroRNAs; Microscopy, Fluorescence; PTEN Phosphohydrolase; Plasmids; Pseudogenes; Staining and Labeling; Transfection; Tumor Suppressor Proteins
PubMed: 34165715
DOI: 10.1007/978-1-0716-1503-4_11 -
Genes, Chromosomes & Cancer Jan 2024PMS2 germline pathogenic variants are one of the major causes for Lynch syndrome and constitutional mismatch repair deficiencies. Variant identification in the 3' region...
PMS2 germline pathogenic variants are one of the major causes for Lynch syndrome and constitutional mismatch repair deficiencies. Variant identification in the 3' region of this gene is complicated by the presence of the pseudogene PMS2CL which shares a high sequence homology with PMS2. Consequently, short-fragment screening strategies (NGS, Sanger) may fail to discriminate variant's gene localization. Using a comprehensive analysis strategy, we assessed 42 NGS-detected variants in 76 patients and found 32 localized on PMS2 while 6 on PMS2CL. Interestingly, four variants were detected in either of them in different patients. Clinical phenotype was well correlated to genotype, making it very helpful in variant assessment. Our findings emphasize the necessity of more specific complementary analyses to confirm the gene origin of each variant detected in different individuals in order to avoid variant misinterpretation. In addition, we characterized two PMS2 genomic alterations involving Alu-mediated tandem duplication and gene conversion. Those mechanisms seemed to be particularly favored in PMS2 which contribute to frequent genomic rearrangements in the 3' region of the gene.
Topics: Humans; Mismatch Repair Endonuclease PMS2; Colorectal Neoplasms; Pseudogenes; Colorectal Neoplasms, Hereditary Nonpolyposis; Germ-Line Mutation
PubMed: 37534630
DOI: 10.1002/gcc.23193 -
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 -
Science Advances Jun 2024Mutations in cause Gaucher disease and are the most important genetic risk factor for Parkinson's disease. However, analysis of transcription at this locus is...
Mutations in cause Gaucher disease and are the most important genetic risk factor for Parkinson's disease. However, analysis of transcription at this locus is complicated by its highly homologous pseudogene, . We show that >50% of short RNA-sequencing reads mapping to also map to . Thus, we used long-read RNA sequencing in the human brain, which allowed us to accurately quantify expression from both and . We discovered significant differences in expression compared to short-read data and identify currently unannotated transcripts of both and . These included protein-coding transcripts from both genes that were translated in human brain, but without the known lysosomal function-yet accounting for almost a third of transcription. Analyzing brain-specific cell types using long-read and single-nucleus RNA sequencing revealed region-specific variations in transcript expression. Overall, these findings suggest nonlysosomal roles for and with implications for our understanding of the role of in health and disease.
Topics: Humans; Glucosylceramidase; Pseudogenes; Brain; Molecular Sequence Annotation; Parkinson Disease; Gaucher Disease; Sequence Analysis, RNA
PubMed: 38924406
DOI: 10.1126/sciadv.adk1296 -
Toxicological Sciences : An Official... Jul 2017UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that...
UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that Felidae and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous (eg, estrogens, androgens, and bile acids) and exogenous compounds (opioids, non-steroidal anti-inflammatory drugs, and environmental pollutants). However UGT2B activity and genetic background are unknown in carnivore species. Therefore, this study was performed to elucidate the species differences of UGT2Bs. Using typical substrates for UGT2Bs, UGT activity was measured in vitro. In addition, UGT2B genetic features are analyzed in silico. Results of UGT activity measurement indicate marked species differences between dogs and other carnivores (cats, Northern fur seals, Steller sea lions, Harbor seals, and Caspian seals). Dogs have very high Vmax/Km toward estradiol (17-glucuronide), estrone, lorazepam, oxazepam, and temazepam. Conversely, cats and pinniped species (especially Caspian seals and Harbor seals) have very low activities toward these substrates. The results of genetic synteny analysis indicate that Felidae and pinniped species have very small numbers of UGT2B isozymes (one or none) compared with dogs, rodents, and humans. Furthermore, Felidae species have the same nonsense mutation in UGT2B, which suggests that Felidae UGT2B31-like is also a pseudogene in addition to UGT1A6. These findings of lower activity of UGT2B suggest that Felidae and some pinniped species have very low UGT activity toward a wide range of chemicals. These results are important for Felidae and Pinnipedia species that are frequently exposed to drugs and environmental pollutants.
Topics: Animals; Carnivora; Glucuronosyltransferase; Isoenzymes; Microsomes, Liver; Pseudogenes; Substrate Specificity; Xenobiotics
PubMed: 28453659
DOI: 10.1093/toxsci/kfx072 -
Methods in Molecular Biology (Clifton,... 2021The number of complete genome sequences explodes more and more with each passing year. Thus, methods for genome annotation need to be honed constantly to handle the... (Review)
Review
The number of complete genome sequences explodes more and more with each passing year. Thus, methods for genome annotation need to be honed constantly to handle the deluge of information. Annotation of pseudogenes (i.e., gene copies that appear not to make a functional protein) in genomes is a persistent problem; here, we overview pseudogene annotation methods that are based on the detection of sequence homology in genomic DNA.
Topics: Animals; Computational Biology; Genomics; Humans; Molecular Sequence Annotation; Pseudogenes; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology; Software
PubMed: 34165707
DOI: 10.1007/978-1-0716-1503-4_3