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World Journal of Surgical Oncology Mar 2022Pseudogene-derived long non-coding RNAs (lncRNAs) have been reported to act as key regulatory factors of cancers. However, the study focused on pseudogene misato family...
BACKGROUND
Pseudogene-derived long non-coding RNAs (lncRNAs) have been reported to act as key regulatory factors of cancers. However, the study focused on pseudogene misato family member 2 (MSTO2P) in the occurrence and development of colorectal cancer (CRC) remains unclear.
METHODS
CCK-8, colony formation, and transwell assays clarified HT-29 and SW480 cell proliferation and invasion. Furthermore, flow cytometry was carried out to detect cell cycle and cell apoptosis. Subcellular localization assay indicated the location of MSTO2P in HT-29 cells. RIP and CHIP assays clarified the relationship of MSTO2P with target protein and gene in HT-29 cells.
RESULTS
MSTO2P expression was upregulated in CRC tissues and cells. Functional experiments revealed that inhibition of MSTO2P suppressed HT-29 and SW480 cell proliferation and invasion, and promoted cell cycle arrest and cell apoptosis. Besides, MSTO2P epigenetically down-regulated cyclin-dependent kinase inhibitor 1A (CDKN1A) via binding to the enhancer of zeste homolog 2 (EZH2) in the nucleus. At last, rescue experiments proved the anti-tumor effect of inhibition of MSTO2P was partially recovered due to the knockdown of CDKN1A in HT-29 cells.
CONCLUSION
LncRNA MSTO2P promoted colorectal cancer progression through epigenetically silencing CDKN1A mediated by EZH2.
Topics: Cell Line, Tumor; Cell Movement; Colorectal Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Enhancer of Zeste Homolog 2 Protein; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; RNA, Long Noncoding
PubMed: 35346226
DOI: 10.1186/s12957-022-02567-5 -
Biology of Reproduction Aug 2020Male contraception is a very active area of research. Several hormonal agents have entered clinical trials, while potential non-hormonal targets have been brought to... (Review)
Review
Male contraception is a very active area of research. Several hormonal agents have entered clinical trials, while potential non-hormonal targets have been brought to light more recently and are at earlier stages of development. The general strategy is to target genes along the molecular pathways of sperm production, maturation, or function, and it is predicted that these novel approaches will hopefully lead to more selective male contraceptive compounds with a decreased side effect burden. Protein kinases are known to play a major role in signaling events associated with sperm differentiation and function. In this review, we focus our analysis on the testis-specific serine kinase (TSSK) protein family. We have previously shown that members of the family of TSSKs are postmeiotically expressed in male germ cells and in mature mammalian sperm. The restricted postmeiotic expression of TSSKs as well as the importance of phosphorylation in signaling processes strongly suggests that TSSKs have an important role in germ cell differentiation and/or sperm function. This prediction has been supported by the reported sterile phenotype of the Tssk6 knockout (KO) mice and of the double Tssk1 and Tssk2 KO mice and by the male subfertile phenotype observed in a Tssk4 KO mouse model.
Topics: Animals; Contraception; Fertility; Humans; Infertility, Male; Male; Phosphorylation; Protein Serine-Threonine Kinases; Spermatogenesis; Spermatozoa; Testis
PubMed: 32337545
DOI: 10.1093/biolre/ioaa064 -
BMC Cancer Sep 2020There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and...
BACKGROUND
There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and robust pseudogene pairs-based signature for the prognosis of hepatocellular carcinoma (HCC).
METHODS
RNA-sequencing data from 374 HCC patients with clinical follow-up information were obtained from the Cancer Genome Atlas (TCGA) database and used in this study. Survival-related pseudogene pairs were identified, and a signature model was constructed by Cox regression analysis (univariate and least absolute shrinkage and selection operator). All individuals were classified into high- and low-risk groups based on the optimal cutoff. Subgroups analysis of the novel signature was conducted and validated in an independent cohort. Pearson correlation analyses were carried out between the included pseudogenes and the protein-coding genes based on their expression levels. Enrichment analysis was performed to predict the possible role of the pseudogenes identified in the signature.
RESULTS
A 19-pseudogene pair signature, which included 21 pseudogenes, was established. Patients in high-risk group demonstrated an increased the risk of adverse prognosis in the TCGA cohort and the external cohort (all P < 0.001). The novel pseudogene signature was independent of other conventional clinical variables used for survival prediction in HCC patients in the two cohorts revealed by the multivariate Cox regression analysis (all P < 0.001). Subgroup analysis further demonstrated the diagnostic value of the signature across different stages, grades, sexes, and age groups. The C-index of the prognostic signature was 0.761, which was not only higher than that of several previous risk models but was also much higher than that of a single age, sex, grade, and stage risk model. Furthermore, functional analysis revealed that the potential biological mechanisms mediated by these pseudogenes are primarily involved in cytokine receptor activity, T cell receptor signaling, chemokine signaling, NF-κB signaling, PD-L1 expression, and the PD-1 checkpoint pathway in cancer.
CONCLUSION
The novel proposed and validated pseudogene pair-based signature may serve as a valuable independent prognostic predictor for predicting survival of patients with HCC.
Topics: Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Survival Analysis
PubMed: 32938429
DOI: 10.1186/s12885-020-07391-2 -
American Journal of Translational... 2020Preeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and a variety of organ failures, currently lacks effective treatments. Urate (hydroxyiso-)...
OBJECTIVES
Preeclampsia (PE), a pregnancy-specific disorder characterized by hypertension and a variety of organ failures, currently lacks effective treatments. Urate (hydroxyiso-) hydrolase, pseudogene (), which is also a long noncoding RNA (lncRNA), has higher expression in PE placentae than in normal controls and therefore acquires an investigation for the specific mechanism of regulation.
METHODS
Placentae were divided into two groups: those from patients with normal pregnancy (NP) (n = 3) and those from patients with PE (n = 3). Total RNA was extracted from the placentae and differentially expressed lncRNAs and mRNAs in PE and NP were identified by Arraystar Human LncRNA Expression Microarray V4.0 analysis. The microarray data were validated by profiling the noncoding RNA expression of URAHP in NP and PE placental tissues through quantitative real-time PCR (qRT-PCR). Then, we uncover the effect of URAHP on cell proliferation by CCK-8 assay and by 3D colony forming assay. Gene coexpression analysis was conducted to identify mRNAs coexpressed with URAHP. qRT-PCR and western blotting assays were used to measure the expression levels of URAHP and KISS1R in JAR and JET-3 cell lines.
RESULTS
A total of 675 differentially expressed lncRNAs (DELRs) [184 upregulated DELRs and 491 downregulated DELRs] and a total of 205 differently expressed genes (DEGs) [56 upregulated mRNAs and 149 downregulated mRNAs] were finally identified between PE and NP samples through high-throughput sequencing analysis. The expression of lncRNA URAHP was increased significantly in the placentae of women with preeclampsia when compared to those with normal pregnancies. The functional assay suggested that the downregulation of URAHP alters the proliferative capacity of JAR/JET-3 cells and that the overexpression of URAHP promotes the proliferation of HTR-8/SVneo cells. We also determined that URAHP and KISS1R are coexpressed.
CONCLUSION
We demonstrated for the first time that the pseudogene URAHP may be associated with PE. The results of this study provide a new target for the comprehensive treatment of preeclampsia.
PubMed: 32913544
DOI: No ID Found -
Frontiers in Cell and Developmental... 2021A growing number of studies are reporting important roles played by long non-coding RNAs (lncRNAs) in various pathological and physiological processes. LncRNAs are... (Review)
Review
A growing number of studies are reporting important roles played by long non-coding RNAs (lncRNAs) in various pathological and physiological processes. LncRNAs are implicated in numerous genomic regulatory functions at different levels, including regulation of transcription, post-transcriptional processes, genomic stability, and epigenetic genome modifications. Double homeobox A pseudogene 8 (DUXAP8), a novel lncRNA, has been reported to be involved in many cancers, including gastric, colorectal, esophageal, bladder, oral, ovarian, lung, and pancreatic cancers as well as hepatocellular carcinoma (HCC). DUXAP8 plays specific oncogenic roles numerous malignancies promoting pathways. DUXAP8 is frequently dysregulated in multiple cancers, acting as a sponge to downregulate various tumor-suppressing microRNA activities. In this review, we comprehensively explore DUXAP8 expression and prognosis across cancer types, and systematically summarize current evidence concerning the functions and molecular mechanisms of DUXAP8 in tumorigenesis and progression. We conclude that DUXAP8 is a potential biomarker and therapeutic target for multiple cancers.
PubMed: 34631702
DOI: 10.3389/fcell.2021.709069 -
Journal of Oncology 2022Alterations in the methylation state of pseudogenes may serve as clinically useful biomarkers of glioblastomas (GBMs) that do not have glioma-CpG island methylator...
OBJECTIVE
Alterations in the methylation state of pseudogenes may serve as clinically useful biomarkers of glioblastomas (GBMs) that do not have glioma-CpG island methylator phenotype (G-CIMP).
METHODS
Non-G-CIMP GBM datasets were included for evaluation, and a RISK-score signature was determined from the methylation state of pseudogene loci. Both bioinformatic and experimental analyses were performed for biological validation.
RESULTS
By integrating clinical information with DNA methylation microarray data, we screened a panel of eight CpGs from discovery cohorts of non-G-CIMP GBMs. Each CpG could accurately and independently predict the prognosis of patients under a treatment regime that combined radiotherapy (RT) and temozolomide (TMZ). The 8-CpG signature appeared to show opposite prognostic correlations between patients treated with RT/TMZ and those treated with RT monotherapy. The analyses further indicated that this signature had predictive value for TMZ efficacy because different survival benefits between RT/TMZ and RT therapies were observed in each risk subgroup. The incorporation of other risk factors, such as age and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, with our pseudogene methylation signature could provide precise risk classification. In vitro experimental data revealed that two locus-specific pseudogenes (ZNF767P and CLEC4GP1) may modulate TMZ resistance via distinct mechanisms in GBM cells.
CONCLUSION
The biologically and clinically relevant RISK-score signature, based on pseudogene methylation loci, may offer information for predicting TMZ responses of non-G-CIMP GBMs, that is independent from, but complementary to, MGMT-based approaches.
PubMed: 35712126
DOI: 10.1155/2022/6345160 -
Uirusu 2020RNA viruses do not need to take the form of DNAs, and RNAs alone complete their replication cycles. On the other hand, since the 1970s, it has been known that DNA... (Review)
Review
RNA viruses do not need to take the form of DNAs, and RNAs alone complete their replication cycles. On the other hand, since the 1970s, it has been known that DNA fragments derived from RNA viruses can be detected in RNA virus-infected cells. Furthermore, in this decade, it has become clear that the eukaryotic genomes contain genetic sequences derived from non-retroviral RNA viruses. The DNA sequences derived from these RNA viruses are thought to be generatedby using a transposable mechanism of retrotransposon, such as LINE-1. Many endogenous RNA viral sequences are formed by the same mechanism as processed pseudogenes in eukaryotic cells, but the significance of the production of RNA viral "pseudogenes " in infected cells has not been elucidated. We have discovered endogenous bornavirus-like elements (EBLs), which derived from a negative-sense, single-stranded RNA virus, Bornaviruses, and have studied the evolution and function of EBLs in host animals. The analysis of EBLs provides us a clue to unravel the history of host-RNA virus coexistence. In this review, I overview about the function of endogenous RNA virus sequences, especially EBLs in mammalian genomes, and discuss the significance of endogenization of RNA viruses as viral pseudogenes in evolution.
Topics: Animals; Bornaviridae; Genome; Pseudogenes; RNA; RNA Viruses; RNA, Viral
PubMed: 33967113
DOI: 10.2222/jsv.70.49 -
Bioscience Reports Jul 2021Long noncoding RNAs (lncRNAs) play critical factors in tumor progression and are ectopically expressed in malignant tumors. Until now, lncRNA pituitary...
Long noncoding RNAs (lncRNAs) play critical factors in tumor progression and are ectopically expressed in malignant tumors. Until now, lncRNA pituitary tumor-transforming 3, pseudogene (PTTG3P) biological function in colorectal cancer (CRC) further needs to be clarified. qRT-PCR was used to measure the PTTG3P level and CCK-8, glucose uptake, lactate assay, adenosine triphosphate (ATP) assay, extracellular acidification rate (ECAR) assay, and xenograft mice model were adopted to evaluate the glycolysis and proliferation, and macrophage polarization were determined in CRC cells. Xenograft experiments were utilized to analyze tumor growth. Ectopic expression of PTTG3P was involved in CRC and related to dismal prognosis. Through gain- and loss-of-function approaches, PTTG3P enhanced cell proliferation and glycolysis through YAP1. Further, LDHA knockdown or glycolysis inhibitor (2-deoxyglucose (2-DG), 3-BG) recovered from PTTG3P-induced proliferation. And PTTG3P overexpression could facilitate M2 polarization of macrophages. Silenced PTTG3P decreased the level of inflammatory cytokines TNF-α, IL-1β and IL-6, and low PTTG3P expression related with CD8+ T, NK, and TFH cell infiltration. Besides, hypoxia-inducible factor-1α (HIF1A) could increase PTTG3P expression by binding to the PTTG3P promoter region. Hypoxia-induced PTTG3P contributes to glycolysis and M2 phenotype of macrophage, which proposes a novel approach for clinical treatment.
Topics: Animals; Cell Proliferation; Colorectal Neoplasms; Cytokines; Databases, Genetic; Female; Gene Expression Regulation, Neoplastic; Glycolysis; HCT116 Cells; HT29 Cells; Humans; Inflammation Mediators; Male; Mice, Nude; Middle Aged; Phenotype; Pseudogenes; RNA, Long Noncoding; Signal Transduction; Tumor Burden; Tumor Hypoxia; Tumor Microenvironment; Tumor-Associated Macrophages; Mice
PubMed: 34132347
DOI: 10.1042/BSR20210764 -
Genes Jan 2023Most pseudogenes are generated when an RNA transcript is reverse-transcribed and integrated into the genome at a new location. Pseudogenes are often considered as an...
Most pseudogenes are generated when an RNA transcript is reverse-transcribed and integrated into the genome at a new location. Pseudogenes are often considered as an imperfect and silent copy of a functional gene because of the accumulation of numerous mutations in their sequence. Here we report the presence of , a retrotransposed pseudogene in the mouse genome, which has no disruptions in its coding sequence. We show that this pseudogene is mainly transcribed in testis and can produce a PHF8-PS protein in vivo. As the PHF8-PS protein has a well-conserved JmjC domain, we characterized its enzymatic activity and show that PHF8-PS does not have the intrinsic capability to demethylate H3K9me2 in vitro compared to the parental PHF8 protein. Surprisingly, PHF8-PS does not localize in the nucleus like PHF8, but rather is mostly located at the cytoplasm. Finally, our proteomic analysis of PHF8-PS-associated proteins revealed that PHF8-PS interacts not only with mitochondrial proteins, but also with prefoldin subunits (PFDN proteins) that deliver unfolded proteins to the cytosolic chaperonin complex implicated in the folding of cytosolic proteins. Together, our findings highlighted PHF8-PS as a new pseudogene-derived protein with distinct molecular functions from PHF8.
Topics: Male; Animals; Mice; Transcription Factors; Pseudogenes; Proteomics; Histone Demethylases; Histones
PubMed: 36672913
DOI: 10.3390/genes14010172 -
Plants (Basel, Switzerland) Jan 2022() and () are ethylene responsive factors that regulate the internode elongation of deepwater rice in response to submergence. We previously reported that normal...
() and () are ethylene responsive factors that regulate the internode elongation of deepwater rice in response to submergence. We previously reported that normal cultivated rice lacks genes because the Chromosome 12 region containing genes was deleted from its genome. However, no study has analyzed how the genome defect occurred in that region by comparing normal cultivated rice and deepwater rice. In this study, comparison of the sequence of the end of Chromosome 12, which contains genes, between normal and deepwater rice showed that complicated genome changes such as insertions, deletions, inversions, substitutions, and translocation occurred frequently in this region. In addition to and of deepwater rice, gene prediction analysis identified four genes containing AP2/ERF domains in normal cultivated rice and six in deepwater rice; we called these genes () genes. s and s were present in close proximity to each other, and the s in normal cultivated rice were in tandem. These predicted genes belong to the same AP2/ERF subfamily and were separated into four types: SK1, SK2, SKL3, and SKL4. Sequence comparison indicated that normal cultivated rice possesses a gene with high homology to , which we named . However, none of the predicted s except for s were expressed during submergence. Although s were expressed in both normal and deepwater rice, normal rice does not undergo internode elongation, suggesting that its expression does not contribute to internode elongation. Plants overexpressing , which showed the most homology to , underwent internode elongation similar to plants overexpressing and under normal growth conditions. A yeast one-hybrid assay showed that the C-end of SKL1 has transcription activity, as do the C-ends of SK1 and SK2. Our results suggested that s were derived via gene duplication, but were not expressed and pseudogenized in normal cultivated rice during sequence evolution.
PubMed: 35161357
DOI: 10.3390/plants11030376