Herpesvirus-encoded microRNAs alter transcriptome of oral keratinocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107005 | GEO | 2018/02/15
REPOSITORIES: GEO
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Project description:Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as etiological factor. However, the underlying mechanisms remains obscure. In our recent miRNA profiling of healthy and diseased human tooth pulpal, elevated expression of HHV encoded v-miRs were identified. Based on the fold induction and significance values, we selected three v-miRs namely miR-K12-3-3p (KSHV), miR-H1 (HSV-1), and miR-UL-70-3p (HCMV) to further examine their impact on host cellular functions. We examined their impact on cellular miRNA profiles of primary human oral keratinocytes (HOK). Our results show differential expression of several host miRNAs in v-miR transfected HOK. High levels of v-miRs were detected in exosomes derived from v-miR transfected HOK as well as the latent KSHV infected cell lines. We show that HOK derived exosomes release their contents into macrophages (Mφ) and alter expression of endogenous miRNAs.
2018-03-31 | GSE107674 | GEO
Project description:MicroRNAs are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding to 3’UTRs of target mRNAs. Kaposi’s sarcoma-associated herpesvirus (KSHV), a virus linked to malignancies including primary effusion lymphoma (PEL), encodes 12 miRNA genes, but only a few regulatory targets are known. We found that KSHV-miR-K12-11 shares 100% seed-sequence homology with hsa-miR-155, a miRNA frequently found up-regulated in lymphomas and critically important for B cell development. Based on this seed-sequence homology, we hypothesized that both miRNAs regulate a common set of target genes and as a result, could have similar biological activities. Examination of five PEL lines showed that PELs do not express miR-155, but do express high levels of miR-K12-11. Bioinformatics tools predicted the transcriptional repressor BACH-1 to be targeted by both miRNAs and ectopic expression of either miR-155 or miR-K12-11 inhibited a BACH-1 3'UTR containing reporter. . Furthermore, BACH-1 protein levels are low in cells expressing either miRNA. Gene expression profiling of miRNA-expressing stable cell lines revealed 66 genes that were commonly down-regulated. For select genes, miRNA targeting was confirmed by reporter assays. Thus, based on our in silico predictions, reporter assays, and expression profiling data, miR-K12-11 and miR-155 regulate a common set of cellular targets. Given the role of miR-155 during B cell maturation, we speculate that miR-K12-11 may contribute to the distinct developmental phenotype of PEL cells, which are blocked in a late stage of B cell development. Together, these findings indicate that KSHV miR-K12-11 is an ortholog of miR-155. Keywords: comparison, experiemental versus control
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Project description:In a major study, we found that miR-aU14, a potential miRNA expressed by human herpesvirus 6A (HHV-6A), acts to selectively inhibit the processing of members of the human miR-30 family through direct RNA:RNA interaction and causes changes in mitochondrial arcchitecture through p53-Drp1 axis. In order to characterize miR-aU14, we carried out differentia lRNA-seq (dRNA-seq) from HHV-6A lytic infected HSB2 cells.
2022-02-17 | GSE179866 | GEO
Project description:In a major study, we found that miR-aU14, a potential miRNA expressed by human herpesvirus 6A (HHV-6A), acts to selectively inhibit the processing of members of the human miR-30 family through direct RNA:RNA interaction and causes changes in mitochondrial arcchitecture through p53-Drp1 axis. In order to characterize miR-aU14 during virus reactivation, we carried out small RNA-seq from U2-OS cells carrying latent HHV-6A. Virus reactivation was carried out using 80 ng/ml of Trichostatin-A (TSA).
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Project description:In a major study, we found that miR-aU14, a potential miRNA expressed by human herpesvirus 6A (HHV-6A), acts to selectively inhibit the processing of members of the human miR-30 family through direct RNA:RNA interaction and causes changes in mitochondrial arcchitecture through p53-Drp1 axis. In order to characterize miR-aU14 during virus reactivation, we carried out small RNA-seq from U2-OS cells carrying latent HHV-6A. Virus reactivation was carried out using 80 ng/ml of Trichostatin-A (TSA).
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Project description:Roseolovirus, or human herpesvirus 6 (HHV-6) is a ubiquitous human pathogen infecting over 95% of the population by the age of two years. As with other herpesviruses, reactivation of HHV-6 can present with severe complications in immunocompromised individuals. Recent studies have highlighted the importance of herpesvirus-derived micro (mi)RNAs in modulating both cellular and viral gene expression. An initial report, which computed the likelihood of various viruses to encode for miRNAs, did not predict HHV-6 miRNAs. To experimentally screen for small HHV-6 encoded RNAs, we conducted large-scale sequencing of Sup-T-1 cells lytically infected with a laboratory strain of HHV-6B. This revealed an abundant 60-65 nucleotide RNA of unknown function derived from the lytic origin of replication (OriLyt) that gave rise to smaller RNA species of 18-19 nucleotides in length. In addition, we identified four pre-miRNAs, whose mature forms accumulated in Argonaute 2. In contrast to other beta-herpesviruses, HHV-6B miRNAs are expressed from direct repeat regions (DRL and DRR) located at either side of the genome. All miRNAs are conserved in the closely related HHV-6A variant, and one of them is a seed ortholog of the human miR-582-5p. Similar to alpha-herpesvirus miRNAs, they are expressed antisense to immediate early ORFs and thus have the potential to regulate key viral regulators. Small RNA sequencing from total RNA or Ago2 associated small RNAs extracted from HHV-6 infected Sup-T-1 cells
2012-01-01 | E-GEOD-34196 | biostudies-arrayexpress
Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks.
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Project description:MicroRNAs are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding to 3âUTRs of target mRNAs. Kaposiâs sarcoma-associated herpesvirus (KSHV), a virus linked to malignancies including primary effusion lymphoma (PEL), encodes 12 miRNA genes, but only a few regulatory targets are known. We found that KSHV-miR-K12-11 shares 100% seed-sequence homology with hsa-miR-155, a miRNA frequently found up-regulated in lymphomas and critically important for B cell development. Based on this seed-sequence homology, we hypothesized that both miRNAs regulate a common set of target genes and as a result, could have similar biological activities. Examination of five PEL lines showed that PELs do not express miR-155, but do express high levels of miR-K12-11. Bioinformatics tools predicted the transcriptional repressor BACH-1 to be targeted by both miRNAs and ectopic expression of either miR-155 or miR-K12-11 inhibited a BACH-1 3'UTR containing reporter. . Furthermore, BACH-1 protein levels are low in cells expressing either miRNA. Gene expression profiling of miRNA-expressing stable cell lines revealed 66 genes that were commonly down-regulated. For select genes, miRNA targeting was confirmed by reporter assays. Thus, based on our in silico predictions, reporter assays, and expression profiling data, miR-K12-11 and miR-155 regulate a common set of cellular targets. Given the role of miR-155 during B cell maturation, we speculate that miR-K12-11 may contribute to the distinct developmental phenotype of PEL cells, which are blocked in a late stage of B cell development. Together, these findings indicate that KSHV miR-K12-11 is an ortholog of miR-155. Experiment Overall Design: 12 samples, 4 experiemental (miR-155 ), 4 experimental (miR-K12-11) and 4 reference controls (pCDNA3.1)
2008-06-16 | E-GEOD-9264 | biostudies-arrayexpress
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Project description:Roseolovirus, or human herpesvirus 6 (HHV-6) is a ubiquitous human pathogen infecting over 95% of the population by the age of two years. As with other herpesviruses, reactivation of HHV-6 can present with severe complications in immunocompromised individuals. Recent studies have highlighted the importance of herpesvirus-derived micro (mi)RNAs in modulating both cellular and viral gene expression. An initial report, which computed the likelihood of various viruses to encode for miRNAs, did not predict HHV-6 miRNAs. To experimentally screen for small HHV-6 encoded RNAs, we conducted large-scale sequencing of Sup-T-1 cells lytically infected with a laboratory strain of HHV-6B. This revealed an abundant 60-65 nucleotide RNA of unknown function derived from the lytic origin of replication (OriLyt) that gave rise to smaller RNA species of 18-19 nucleotides in length. In addition, we identified four pre-miRNAs, whose mature forms accumulated in Argonaute 2. In contrast to other beta-herpesviruses, HHV-6B miRNAs are expressed from direct repeat regions (DRL and DRR) located at either side of the genome. All miRNAs are conserved in the closely related HHV-6A variant, and one of them is a seed ortholog of the human miR-582-5p. Similar to alpha-herpesvirus miRNAs, they are expressed antisense to immediate early ORFs and thus have the potential to regulate key viral regulators.
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