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Medical Science Monitor : International... Feb 2019BACKGROUND The POU domain class 5 transcription factor 1B (POU5F1B), is a pseudogene that is homologous to octamer-binding transcription factor 4 (OCT4), and is located...
The Octamer-Binding Transcription Factor 4 (OCT4) Pseudogene, POU Domain Class 5 Transcription Factor 1B (POU5F1B), is Upregulated in Cervical Cancer and Down-Regulation Inhibits Cell Proliferation and Migration and Induces Apoptosis in Cervical Cancer Cell Lines.
BACKGROUND The POU domain class 5 transcription factor 1B (POU5F1B), is a pseudogene that is homologous to octamer-binding transcription factor 4 (OCT4), and is located adjacent to the MYC gene on human chromosome 8q24. POU5F1B has been reported to be transcribed in several types of cancer, but its role in cervical cancer remains unclear. This study aimed to investigate the expression and function of POU5F1B in tissue samples of human cervical cancer and in cervical cancer cell lines in vitro. MATERIAL AND METHODS Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify POU5F1B expression in cervical cancer tissues and in SiHa, HeLa, CaSki, and C33A human cervical cancer cell lines. Functional in vitro studies included analysis of the effects of POU5F1B expression on cervical cancer cell proliferation, migration, and apoptosis using a Cell Counting Kit-8 (CCK-8) assay, cell migration assays, and flow cytometry. Luciferase activity assays, qRT-PCR, and Western blot were performed to confirm the expression of POU5F1B. RESULTS POU5F1B was significantly upregulated in cervical cancer tissues and cell lines. Interference with the expression of POU5F1B significantly inhibited cell proliferation, apoptosis, migration and invasion, and induced apoptosis in vitro. Western blot demonstrated that POU5F1B could modulate the expression of the OCT4 protein. CONCLUSIONS POU5F1B was upregulated in cervical cancer and down-regulation inhibited cell proliferation and migration and induced apoptosis in cervical cancer cell lines by modulating OCT4. Further studies are required to determine whether POU5F1B might be a diagnostic or prognostic biomarker or therapeutic target in cervical cancer.
Topics: Adult; Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Female; G1 Phase Cell Cycle Checkpoints; Gene Knockdown Techniques; Genes, myc; HeLa Cells; Heterografts; Homeodomain Proteins; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Octamer Transcription Factor-3; Pseudogenes; Up-Regulation; Uterine Cervical Neoplasms
PubMed: 30762028
DOI: 10.12659/MSM.912109 -
International Journal of Molecular... Aug 2020YRNAs are a type of short, noncoding RNAs. A total of four different transcripts can be distinguished, which are , , and . All YRNAs are relatively small, made up of... (Review)
Review
YRNAs are a type of short, noncoding RNAs. A total of four different transcripts can be distinguished, which are , , and . All YRNAs are relatively small, made up of about 100 nucleotides each. YRNAs are characterized by a stem-loop structure and each part of that structure carries a different function. YRNAs are transcribed in the nucleus by RNA polymerase III. Then, the YRNA molecule is bound to the polyuridine tail of the La protein responsible for both its nuclear retention and protection from degradation. They also bind to the Ro60 protein, making the molecule more stable. In turn, YRNA-derived small RNAs (YsRNAs) are a class of YRNAs produced in apoptotic cells as a result of YRNA degradation. This process is performed by caspase-3-dependent pathways that form two groups of YsRNAs, with lengths of either approximately 24 or 31 nucleotides. From all four YRNA transcripts, 75 well-described pseudogenes are generated as a result of the mutation. However, available data indicates the formation of up to 1000 pseudogenes. YRNAs and YRNA-derived small RNAs may play a role in carcinogenesis due to their altered expression in cancers and influence on cell proliferation and inflammation. Nevertheless, our knowledge is still limited, and more research is required. The main aim of this review is to describe the current state of knowledge about YRNAs, their function and contribution to carcinogenesis, as well as their potential role in cancer diagnostics. To confirm the promising potential of YRNAs and YRNA-derived fragments as biomarkers, their significant role in several tumor types was taken into consideration.
Topics: Biomarkers, Tumor; Biomedical Research; Humans; Neoplasms; Nucleic Acid Conformation; Pseudogenes; RNA, Long Noncoding
PubMed: 32784396
DOI: 10.3390/ijms21165682 -
Aging Oct 2022Pseudogenes are barely transcribed at normal, while the anomalous transcripts of them are mostly regarded as long non-coding RNAs (lncRNAs), which play potential...
Pseudogenes are barely transcribed at normal, while the anomalous transcripts of them are mostly regarded as long non-coding RNAs (lncRNAs), which play potential functions in human tumorigenicity and development. The exact effects of pseudogene-derived transcripts on hepatocellular carcinoma (HCC) are ambiguous. According to our previous research and constructed database on the HCC-related lncRNAs, we noticed that UBE2MP1 was transcriptionally activated in HCC as a pseudogene from the ubiquitin-conjugating enzyme member UBE2M. In this study, we validated the high expression of the UBE2MP1 transcript in HCC and its adverse correlation with dismal outcomes for the patients. UBE2MP1 depletion at the transcript level significantly impaired cell proliferation and apoptosis resistance in HCC cell lines. Notably, we discovered that the UBE2MP1 transcript shared a specific sequence, binding to the miR-145-5p seed region with a typical ceRNA effect. Simultaneously, we verified an axis of miR-145-5p/RGS3 in HCC cells, which promoted cell proliferation and apoptosis resistance with significance. And modulation of UE2MP1 could remarkably affect RGS3 expression and consequentially influence HCC cell growth . And combined with the rescue experiment modulating either miR-145-5p or RGS3 furtherly indicated UBE2MP1 as an upstream regulator of the axis in promoting HCC cell growth and maintenance. Thus, our findings provide new strategies for HCC prevention and individual treatment.
Topics: Humans; Carcinoma, Hepatocellular; RNA, Long Noncoding; Liver Neoplasms; Pseudogenes; Gene Expression Regulation, Neoplastic; MicroRNAs; Ubiquitin-Conjugating Enzymes; Cell Proliferation; Apoptosis; Cell Line; RGS Proteins
PubMed: 36214767
DOI: 10.18632/aging.204319 -
Theranostics 2022N6-methyladenosine (mA) is involved in critical cancerous processes. Pseudogenes play various roles in carcinogenesis and progression. However, the functional roles of...
N6-methyladenosine (mA) is involved in critical cancerous processes. Pseudogenes play various roles in carcinogenesis and progression. However, the functional roles of mA-associated pseudogenes in head and neck squamous cell carcinoma (HNSCC) are largely unknown. We systematically analyzed the mRNA profile of 24 mA regulators and 13931 pseudogenes from The Cancer Genome Atlas HNSCC dataset and ultimately identified 10 mA-associated prognostic pseudogenes, which were validated in the Gene Expression Omnibus and our hospital datasets. Based on the risk score of mA-associated pseudogenes, comprehensive analytical frameworks and experimental validation were implemented among pseudogene-defined low-/high-risk subtypes. Here, we found expression pattern of mA-associated pseudogenes was significantly associated with infiltrating immune cell compositions, and the expression of antitumor immune response markers, including T cell exhaustion, antigen presentation, interferon, and kinase genes. The mA-associated pseudogenes, which had dramatic mA peaks and higher mA levels, could regulate the expression of targeted immune-involved genes through miRNAs. We experimentally validate the oncogene PDIA3P1, and tumor-suppressor RRN3P3, which promote the RNA and protein expression of their targeted immune-involved genes AKT1 and EZH2 via miR-34a-5p and miR-26b-5p, respectively. Moreover, HNSCC patients in the high-risk subtype could benefit more from immune checkpoint inhibitors therapy. Furthermore, doxorubicin and topotecan were considered to hold the most promising therapeutic potential robustly in silico evidence and experiments for HNSCC patients in the high-risk subtype. Our discovery revealed that the 10 mA-associated prognostic pseudogenes significantly contribute to predicting immunotherapy benefits and therapeutic agents, which might bring some potential implications for both immunotherapy and chemotherapy in HNSCC.
Topics: Humans; Adenosine; Head and Neck Neoplasms; Immunologic Factors; Immunotherapy; MicroRNAs; Prognosis; Pseudogenes; Squamous Cell Carcinoma of Head and Neck
PubMed: 36438489
DOI: 10.7150/thno.76689 -
Disease Markers 2019Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2...
OBJECTIVE
Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2 (annexin A2 pseudogene 2) is one of three pseudogenes of annexin A2 that have recently been shown to be aberrantly transcribed in hepatocellular carcinoma (HCC) cells. However, its clinical meaning and biological function in HCC have remained unclear. Therefore, the present study was aimed at exploring the prognostic value of a high expression of ANXA2P2 in HCC tissue and at identifying whether it can affect the efficacy of targeted drugs (sorafenib, regorafenib, and lenvatinib).
METHODS
We obtained ANXA2P2 mRNA expression levels from The Cancer Genome Atlas (TCGA) RNA sequence database. The expression levels of ANXA2P2 in 49 pairs of intratumoral and peritumoral liver tissues were examined by RT-PCR. Wound healing and transwell assays were performed to confirm the tumor-promoting properties of ANXA2P2 in HCC cells. CCK8 assay was conducted to identify whether ANXA2P2 can affect the growth of HCC cells when administered with targeted drugs (sorafenib, regorafenib, and lenvatinib).
RESULTS
The expression of ANXA2P2 in HCC tissues was significantly higher than that in adjacent cancerous tissues from TCGA database and validation group. Additionally, patients with high ANXA2P2 expression in HCC tissue had a shorter overall survival, whereas no statistically significant correlation was found between ANXA2P2 expression and disease-free survival ( = 0.08) as well as other clinical parameters, such as age, gender, histological grade, T classification, stage, albumin level, alpha-fetoprotein, and vascular invasion ( = 0.7323, 0.8807, 0.5762, 0.8515, 0.7113, 0.242, 1.0000, and 0.7685, respectively). Furthermore, experiments showed that knockdown of ANXA2P2 inhibited migration and invasion of HCC cells but did not have an influence on the HCC cell proliferation when treated with targeted drugs (sorafenib, regorafenib, and lenvatinib).
CONCLUSION
Our study confirmed elevated ANXA2P2 expression levels in HCC tissue compared with adjacent noncancerous tissue and a worse prognosis of patients with high ANXA2P2 levels in the HCC tissue. The newly found properties of promoting migration and invasion of ANXA2P2 in HCC help to explain this phenomenon. ANXA2P2 could be a novel and suitable predicative biomarker for the risk assessment of recurrence or metastasis of HCC patients but may not be effective to predict the efficacy of targeted drugs.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Annexin A2; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Line, Tumor; Female; Hepatocytes; Humans; Liver Neoplasms; Male; Middle Aged; Phenotype; Pseudogenes
PubMed: 30881525
DOI: 10.1155/2019/9267046 -
PloS One 2018NANOG has been demonstrated to play an essential role in the maintenance of embryonic stem cells, and its pseudogene, NANOGP8, is suggested to promote the cancer stem...
NANOG has been demonstrated to play an essential role in the maintenance of embryonic stem cells, and its pseudogene, NANOGP8, is suggested to promote the cancer stem cell phenotype. As the roles of these genes are intimately involved with glioblastoma multiforme progression and exosomes are critical in intercellular communication, we conducted a detailed analysis of the association of the NANOG gene family with exosomes to identify diagnostic markers for cancer. Exosomes were precipitated from conditioned culture media from various cell lines, and NANOG gene fragments were directly amplified without DNA isolation using multiple primer sets. The use of the enzymes AlwNI and SmaI with restriction fragment length polymorphism analysis functioned to distinguish NANOGP8 from other NANOG family members. Collectively, results suggest that the NANOG DNA associated with exosomes is not full length and that mixed populations of the NANOG gene family exist. Furthermore, sequence analysis of exosomal DNA amplified with a NANOGP8 specific primer set frequently showed an insertion of a 22 bp sequence into the 3' UTR. The occurrence rate of this insertion was significantly higher in exosomal DNA clones from cancer cells as compared to normal cells. We have detected mixed populations of NANOG DNA associated with exosomes and have identified preferential modulations in the sequences from cancer samples. Our findings, coupled with the properties of exosomes, may allow for the detection of traditionally inaccessible cancers (i.e. GBM) through minimally invasive techniques. Further analysis of exosomal DNA sequences of NANOG and other embryonic stemness genes (OCT3/4, SOX2, etc.) may establish a robust collection of exosome based diagnostic markers, and further elucidate the mechanisms of cancer formation, progression, and metastasis.
Topics: 3' Untranslated Regions; Biomarkers, Tumor; Brain Neoplasms; Cell Line, Tumor; Coculture Techniques; Culture Media, Conditioned; Exosomes; Gene Expression Regulation, Neoplastic; Glioblastoma; HEK293 Cells; Humans; Multigene Family; Mutagenesis, Insertional; Nanog Homeobox Protein; Pseudogenes
PubMed: 29787607
DOI: 10.1371/journal.pone.0197782 -
BMC Genomics Jan 2024Buruli ulcer (BU) disease, caused by Mycobacterium ulcerans (MU), and characterized by necrotic ulcers is still a health problem in Africa and Australia. The genome of...
BACKGROUND
Buruli ulcer (BU) disease, caused by Mycobacterium ulcerans (MU), and characterized by necrotic ulcers is still a health problem in Africa and Australia. The genome of the bacterium has several pseudogenes due to recent evolutionary events and environmental pressures. Pseudogenes are genetic elements regarded as nonessential in bacteria, however, they are less studied due to limited available tools to provide understanding of their evolution and roles in MU pathogenicity.
RESULTS
This study developed a bioinformatic pipeline to profile the pseudogenomes of sequenced MU clinical isolates from different countries. One hundred and seventy-two MU genomes analyzed revealed that pseudogenomes of African strains corresponded to the two African lineages 1 and 2. Pseudogenomes were lineage and location specific and African lineage 1 was further divided into A and B. Lineage 2 had less relaxation in positive selection than lineage 1 which may signify different evolutionary points. Based on the Gil-Latorre model, African MU strains may be in the latter stages of evolutionary adaption and are adapting to an environment rich in metabolic resources with a lower temperature and decreased UV radiation. The environment fosters oxidative metabolism and MU may be less reliant on some secondary metabolites. In-house pseudogenomes from Ghana and Cote d'Ivoire were different from other African strains, however, they were identified as African strains.
CONCLUSION
Our bioinformatic pipeline provides pseudogenomic insights to complement other whole genome analyses, providing a better view of the evolution of the genome of MU and suggest an adaptation model which is important in understanding transmission. MU pseudogene profiles vary based on lineage and country, and an apparent reduction in insertion sequences used for the detection of MU which may adversely affect the sensitivity of diagnosis.
Topics: Humans; Africa; Australia; Black People; Mycobacterium ulcerans; Pseudogenes; Buruli Ulcer
PubMed: 38253991
DOI: 10.1186/s12864-024-10001-1 -
Oxidative Medicine and Cellular... 2022Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in...
OBJECTIVE
Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in gliomas. However, its biological function in gliomas remains unclear.
METHODS
In this study, we analyzed clinical data on patients with glioma obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx), and the GEPIA2 databases. We used the R language for the main analysis. Correlations among RPL4P4 expression, pathological characteristics, clinical outcome, and biological function were evaluated. In addition, the correlations of RPL4P4 expression with immune cell infiltration and glioma progression were analyzed. Finally, wound healing, Transwell, and CCK-8 assays were performed to analyze the function of RPL4P4 in glioma cells.
RESULT
We found that RPL4P4 is highly expressed in glioma tissues and is associated with poor prognosis, IDH1 wild type, codeletion of 1p19q, and age. Multivariate analysis and the nomogram model showed that high RPL4P4 expression was an independent risk factor for glioma prognosis and had better prognostic prediction power. Moreover, high RPL4P4 expression correlated with immune cell infiltration, which showed a significant positive association with M2-type macrophages. Finally, RPL4P4 knockdown in glioma cell lines caused decreased glioma cell proliferation, invasion, and migration capacity.
CONCLUSION
Our data suggest that RPL4P4 can function as an independent prognostic predictor of glioma. It also shows that RPL4P4 expression correlates with immune cell infiltration and that targeting RPL4P4 may be a new strategy for the treatment of glioma patients.
Topics: Biomarkers; Brain Neoplasms; Glioma; Humans; Prognosis; Pseudogenes; Ribosomal Proteins
PubMed: 35993018
DOI: 10.1155/2022/7967722 -
Oncogene Jul 2021Research over the past decade has suggested important roles for pseudogenes in glioma. This study aimed to show that pseudogene PRELI domain-containing 1 pseudogene 6...
Research over the past decade has suggested important roles for pseudogenes in glioma. This study aimed to show that pseudogene PRELI domain-containing 1 pseudogene 6 (PRELID1P6) promotes glioma progression. Aberrant expression of genes was screened using The Cancer Genome Atlas database. We found that mRNA level of PRELID1P6 was highly upregulated in glioma and was associated with a shorter survival time. Functional studies showed that the knockdown of PRELID1P6 decreased cell proliferation, sphere formation, and clone formation ability and blocked the cell cycle transition at G0/G1, while overexpression of PRELID1P6 had the opposite effects. Mechanistically, knockdown of PRELID1P6 changed the cellular localization of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) from nucleus to cytoplasm, which promoted ubiquitin-mediated degradation of hnRNPH1. RNA-sequence and gene set enrichment analysis suggested that knockdown of PRELID1P6 regulates the apoptosis signaling pathway. Western blotting showed that PRELID1P6 increased TRF2 expression by hnRNPH1-mediated alternative splicing effect and activated the Akt/mTOR pathway. Furthermore, Akt inhibitor MK2206 treatment reversed the oncogenic function of PRELID1P6. PRELID1P6 was also found to be negatively regulated by miR-1825. Our result showed that PRELID1P6 promotes glioma progression through the hnHNPH1-Akt/mTOR pathway. These findings shed new light on the important role of PRELID1P6 as a novel oncogene for glioma.
Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Female; Glioma; Heterocyclic Compounds, 3-Ring; Heterogeneous-Nuclear Ribonucleoproteins; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondrial Proteins; Proto-Oncogene Proteins c-akt; Pseudogenes; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 34108621
DOI: 10.1038/s41388-021-01854-x -
Journal of Molecular Evolution Jan 2018In archaea, pseudouridine (Ψ) synthase Pus10 modifies uridine (U) to Ψ at positions 54 and 55 of tRNA. In contrast, Pus10 is not found in bacteria, where modifications...
In archaea, pseudouridine (Ψ) synthase Pus10 modifies uridine (U) to Ψ at positions 54 and 55 of tRNA. In contrast, Pus10 is not found in bacteria, where modifications at those two positions are carried out by TrmA (U54 to mU54) and TruB (U55 to Ψ55). Many eukaryotes have an apparent redundancy; their genomes contain orthologs of archaeal Pus10 and bacterial TrmA and TruB. Although eukaryal Pus10 genes share a conserved catalytic domain with archaeal Pus10 genes, their biological roles are not clear for the two reasons. First, experimental evidence suggests that human Pus10 participates in apoptosis induced by the tumor necrosis factor-related apoptosis-inducing ligand. Whether the function of human Pus10 is in place or in addition to of Ψ synthesis in tRNA is unknown. Second, Pus10 is found in earlier evolutionary branches of fungi (such as chytrid Batrachochytrium) but is absent in all dikaryon fungi surveyed (Ascomycetes and Basidiomycetes). We did a comprehensive analysis of sequenced genomes and found that orthologs of Pus10, TrmA, and TruB were present in all the animals, plants, and protozoa surveyed. This indicates that the common eukaryotic ancestor possesses all the three genes. Next, we examined 116 archaeal and eukaryotic Pus10 protein sequences to find that Pus10 existed as a single copy gene in all the surveyed genomes despite ancestral whole genome duplications had occurred. This indicates a possible deleterious gene dosage effect. Our results suggest that functional redundancy result in gene loss or neofunctionalization in different evolutionary lineages.
Topics: Amino Acid Sequence; Animals; Archaea; Bacteria; Base Sequence; Biological Evolution; Escherichia coli Proteins; Eukaryota; Evolution, Molecular; Humans; Hydro-Lyases; Intramolecular Transferases; Phylogeny; Pseudogenes; RNA, Transfer; tRNA Methyltransferases
PubMed: 29349599
DOI: 10.1007/s00239-018-9827-y