Effect of Overexpression of VIRMA on m6A-methylated mRNAs in breast cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205892 | GEO | 2023/08/03
REPOSITORIES: GEO
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Project description:Several studies revealed an underlying disordered m6A regulatory network in human nasopharyngeal carcinoma (NPC). However, the roles of m6A regulators and sequential m6A dysregulation in NPC remain largely unknown. In the present study, we investigated the role of VIRMA and its underlying mechanisms in NPC. We performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) to identify the potential downstream targets of VIRMA that might be essential in NPC using HONE-1 cells with or without VIRMA silenced (two biological replicates).
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Project description:In order to determine whether increased m6A abundance coupled with upregulation of transcripts regulating UPR also promote their translation, we first compared levels of key UPR signalling proteins in VIRMA FL-overexpressing SKBR3 cells and eGFP control. To our surprise, none of the key UPR signalling proteins measured showed increased levels in VIRMA FL cells compared to control We then performed ribosome profiling analysis between SKBR cells overexpressing VIRMA FL and eGFP control
2023-08-03 | GSE205873 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant internal RNA modification in mRNA molecules and plays important roles in multiple important biological processes including cancer development. KIAA1429/VIRMA is an important component of m6A methyltransferase complex to facilitate depositing m6A modification in RNA molecules. Here we found that KIAA1429/VIRMA was overexpressed in breast cancer patients among other m6A related enzymes. Breast cancer patients with higher KIAA1429 expression have worse survival compared with control group. In addition, KIAA1429/VIRMA protein mislocated in cytosol in breast cancer tissues and cell lines. KIAA1429/VIRMA depletion reduced breast cancer cell proliferation and migration. Mechanism studies showed that cytosolic expressed KIAA1429/VIRMA interacted with m6A reader protein IGF2BP3 and stabilized expression of m6A-modified HAS2 expression. HAS2 is downstream of KIAA1429/VIRMA to mediate breast cancer cell proliferation and migration and has positive correlation with KIAA1429/VIRMA expression in cancer patients.
2021-11-02 | GSE185494 | GEO
Project description:N6-methyadenosine (m6A) is enriched in 3`UTR (3` untranslated region) and near stop codon of mature polyadenylated mRNAs in mammalian systems and has regulatory roles in eukaryotic mRNA transcriptome switch. Significantly, the mechanism for this modification preference remains unknown, however. Herein we report a characterization of the full m6A methyltransferase complex in HeLa cells identifying METTL3/METTL14/WTAP/VIRMA/HAKAI/ZC3H13 as the key components, and we show that VIRMA mediates preferential mRNA methylation in 3`UTR and near stop codon. Biochemical studies reveal that VIRMA recruits the catalytic core components METTL3/METTL14/WTAP to guide region-selective methylations. Around 60% of VIRMA mRNA immunoprecipitation targets manifest strong m6A enrichment in 3`UTR. Depletions of VIRMA and METTL3 induce 3`UTR lengthening of several hundred mRNAs with over 50% targets in common. VIRMA associates with polyadenylation cleavage factors CPSF5 and CPSF6 in an RNA-dependent manner. Depletion of CPSF5 leads to significant shortening of 3`UTR of over 2,800 mRNAs, 84% of which are modified with m6A. Together our studies provide insights into m6A deposition specificity in 3`UTR and its correlation with alternative polyadenylation.
2018-03-07 | GSE102493 | GEO
Project description:To confirm the contribution of elevated VIRMA levels towards cell proliferation and colony formation, we depleted VIRMA in four breast cancer cell lines, SKBR3, HS578T, MCF7 and MDAMB453 using short-hairpin RNAs (shRNAs). We then performed gene expression profiling analysis using data obtained from RNA-seq data
2023-08-03 | GSE205855 | GEO
Project description:Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the recent finding of FTO?s (Fat Mass Obesity) N6-methyl-adenosine (m6A) deaminase activity, thus suggested a link between obesity-associated diseases and the presence of m6A in mRNA. Another catalyst of the sudden rise in mRNA methylation research was the release of mRNA methylomes for human, mouse and Saccharomyces cerevisiae. However, the molecular function, or functions of this mRNA ?epimark? remain to be discovered. There is supportive evidence that m6A could be a mark for mRNA degradation due to its binding to YTH domain proteins, and consequently being chaperoned to P bodies. Nonetheless, only a subpopulation of the methylome was found binding to YTHDF2 in HeLa cells. The model organism Saccharomyces cerevisiae, has only one YTH domain protein (Pho92, Mrb1), which targets PHO4 transcripts for degradation under phosphate starvation. However, mRNA methylation is only found under meiosis inducing conditions, and PHO4 transcripts are apparently non-methylated. In this paper we set out to investigate if m6A could function alternatively to being a degradation mark in S. cerevisiae, we also sought to test whether it can be induced under non-standard sporulation conditions. We find associations between the presence of m6A and message translatability. We also find m6A induction following prolonged rapamycin treatment. GeneChip analyses were performed to investigate the distribution of early meiotic transcripts (3hours) on different polysome and monosome fractions
2015-08-12 | E-GEOD-68435 | biostudies-arrayexpress
Project description:Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the recent finding of FTO?s (Fat Mass Obesity) N6-methyl-adenosine (m6A) deaminase activity, thus suggested a link between obesity-associated diseases and the presence of m6A in mRNA. Another catalyst of the sudden rise in mRNA methylation research was the release of mRNA methylomes for human, mouse and Saccharomyces cerevisiae. However, the molecular function, or functions of this mRNA ?epimark? remain to be discovered. There is supportive evidence that m6A could be a mark for mRNA degradation due to its binding to YTH domain proteins, and consequently being chaperoned to P bodies. Nonetheless, only a subpopulation of the methylome was found binding to YTHDF2 in HeLa cells. The model organism Saccharomyces cerevisiae, has only one YTH domain protein (Pho92, Mrb1), which targets PHO4 transcripts for degradation under phosphate starvation. However, mRNA methylation is only found under meiosis inducing conditions, and PHO4 transcripts are apparently non-methylated. In this paper we set out to investigate if m6A could function alternatively to being a degradation mark in S. cerevisiae, we also sought to test whether it can be induced under non-standard sporulation conditions. We find associations between the presence of m6A and message translatability. We also find m6A induction following prolonged rapamycin treatment.
2015-08-12 | GSE68435 | GEO
Project description:KIAA1429/VIRMA promotes breast cancer proliferation and migration by stabilizing m6A-modified HAS2 RNA expression in cytosol
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Project description:Dysregulations of long non-coding RNAs (lncRNA) contribute to tumorigenesis by modulating specific cancer-related pathways, but the roles of m6A-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profile, and discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis in vitro and in vivo. Mechanistically, LINC00839 interacted directly with transcription factor, TATA-box binding protein associated factor (TAF15), and coordinated its recruitment to promoter region of amine oxidase copper-containing 1 (AOC1), thereby activating AOC1 transcription in trans. Ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, silencing vir like m6A methyltransferase associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) were found to attenuate the expression level and RNA stability of LINC00839 in an m6A-dependent manner. This study unveils a novel oncogenic VIRMA/IGF2BP1–LINC00839–TAF15–AOC1 axis, and highlights significance and prognostic value of LINC00839 in NPC carcinogenesis.
2023-07-05 | GSE228724 | GEO
Project description:Dysregulations of long non-coding RNAs (lncRNA) contribute to tumorigenesis by modulating specific cancer-related pathways, but the roles of m6A-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profile, and discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis in vitro and in vivo. Mechanistically, LINC00839 interacted directly with transcription factor, TATA-box binding protein associated factor (TAF15), and coordinated its recruitment to promoter region of amine oxidase copper-containing 1 (AOC1), thereby activating AOC1 transcription in trans. Ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, silencing vir like m6A methyltransferase associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) were found to attenuate the expression level and RNA stability of LINC00839 in an m6A-dependent manner. This study unveils a novel oncogenic VIRMA/IGF2BP1–LINC00839–TAF15–AOC1 axis, and highlights significance and prognostic value of LINC00839 in NPC carcinogenesis.
2023-07-05 | GSE228723 | GEO