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Comprehensive investigation of miRNome identifies novel candidate miRNA-mRNA interactions implicated in T-cell acute lymphoblastic leukemia

ABSTRACT: The aim of the study was to characterize the landscape of miRNA expression in 34 samples of pediatric T-cell acute lymphoblastic leukemia (T-ALL) and to identify miRNAs differentially expressed between T-ALL and normal mature T lymphocytes (5 samples).

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Małgorzata Dawidowska

PROVIDER: E-MTAB-7446 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Small RNA-Seq Reveals similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia

Project description:We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several known and putative oncogenes targeted by this miRNA, including KRAS, FGF1, and FGF9. Pathway analysis indicated signaling pathways related to cell growth and proliferation, including FGFR signaling and PI3K-AKT signaling, with the majority of genes overrepresented in these pathways being predicted targets of hsa-miR-143-3p. By luciferase reporter assays, we validated direct interactions of this miRNA with KRAS, FGF1 and FGF9. In cell proliferation assays, we showed reduction of cell growth upon miR-143-3p overexpression in two T-ALL cell lines. Our study is the first description of the miRNA transcriptome in AYA T-ALL patients and the first report on tumor suppressor potential of miR-143-3p in T-ALL. Downregulation of this miRNA in T-ALL patients might contribute to enhanced growth and viability of leukemic cells. We also discuss the potential role of miR-143-3p in FGFR signaling. Although this requires more extensive validation, it might be an interesting direction, since FGFR inhibition proved promising in preclinical studies in various cancers.

2022-09-06 | E-MTAB-11987 | biostudies-arrayexpress

Deep-sequencing influences the results obtained in small-RNA sequencing

Project description:This study presents a comparison of small RNA sequencing libraries generated from the same cell lines but using different sequencing platforms and protocols. The samples were analyzed and compared at the level of miRNAs expression and as a population of small RNAs derived from repetitive elements. Despite a good correlation between sequencing platforms, there are qualitative and quantitative variations in the results depending on the protocol used. 10 samples were examined: 6 from the ES E14 XY cell type: 1 454, 2 SOLiD from 2 technological versions, and 3 SOLEXA from 3 different protocols, and 4 samples from ES PGK XX cells: 1 454 and 1 SOLEXA sample, and 2 SOLiD samples from 2 technological versions.

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microRNA (miRNA) expression profiles of murine polyploid trophoblast giant cells (TGCs) from day 9.5 implantation sites.

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2013-07-28 | E-GEOD-43531 | biostudies-arrayexpress

High-throughput sequencing reveals differential expression of miRNAs in intestine from sea cucumber during aestivation [miRNA-Seq]

Project description:The regulatory role of miRNA in gene expression is an emerging hot new topic in the control of hypometabolism. Sea cucumber aestivation is a complicated physiological process that includes obvious hypometabolism as evidenced by a decrease in the rates of oxygen consumption and ammonia nitrogen excretion, as well as a serious degeneration of the intestine into a very tiny filament. To determine whether miRNAs play an important regulatory roles in this process, the present study analyzed profiles of miRNA expression in the intestine of sea cucumber (Apostichopus japonicus), using Solexa deep sequencing technology. We identified 309 sea cucumber miRNAs, including 19 novel miRNAs specific to sea cucumber. Animals sampled during deep aestivation (DA) after at least 15 days of continuous torpor, were compared with animals from a non-aestivation (NA) state (animals that had passed through aestivation and returned to an active state). We identified 42 differentially expressed miRNAs (RPM (reads per million) >10, |FC| (|fold change|) ≥1, FDR<0.01) during aestivation, which were validated by two other miRNA profiling methods: miRNA microarray and real-time PCR. Among the most prominent miRNA species, miR-200-3p, miR-2004, miR-2010, miR-22, miR-252a, miR-252a-3p and miR-92 were significantly over-expressed during deep aestivation compared with non-aestivation animals. Preliminary analyses of their putative target genes suggest that these miRNAs could play important roles in global transcriptional depression during aestivation. analyze the global profile of small RNAs in non-aestivation (NA) and deep aestivation (DA) sea cucumbers' intestine using Solexa sequencing technology

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2021-10-18 | E-MTAB-10438 | biostudies-arrayexpress

Large-scale identification and comparative analysis of miRNA expression profile in the respiratory tree of the sea cucumber Apostichopus japonicus during aestivation (part 2)

Project description:The sea cucumber Apostichopus japonicus withstands high water temperatures in the summer by suppressing metabolic rate and entering a state of aestivation. We hypothesized that changes in the expression of miRNAs could provide important post-transcriptional regulation of gene expression during hypometabolism via control over mRNA translation. The present study analyzed profiles of miRNA expression in the sea cucumber respiratory tree using Solexa deep sequencing technology. We identified 279 sea cucumber miRNAs, including 15 novel miRNAs specific to sea cucumber. Animals sampled during deep aestivation (DA; after at least 15 days of continuous torpor) were compared with animals from a non-aestivation (NA) state (animals that had passed through aestivation and returned to an active state). We identified 30 differentially expressed miRNAs ([RPM (reads per million) >10, |FC| (|fold change|) ≥1, FDR (false discovery rate) <0.01]) during aestivation, which were validated by two other miRNA profiling methods: miRNA microarray and real-time PCR. Among the most prominent miRNA species, miR-124, miR-124-3p, miR-79, miR-9 and miR-2010 were significantly over-expressed during deep aestivation compared with non-aestivation animals, suggesting that these miRNAs may play important roles in metabolic rate suppression during aestivation. analyze the global profile of small RNAs in non-aestivation (NA) and deep aestivation (DA) sea cucumbers' respiratory tree using Solexa sequencing technology

2014-10-01 | E-GEOD-52225 | biostudies-arrayexpress

MicroRNA-203 represses selection and expansion of oncogenic HRas transformed tumor initiating cells [seq]

Project description:In many mouse models of skin cancer, only a few tumors typically form although many cells competent for tumorigenesis receive the same oncogenic mutations. These observations suggest a selection process for defining tumor initiating cells. Here we use quantitative mRNA- and miR-Seq to determine the impact of HRasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HRasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 with an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for HRas-initiated tumorigenesis. These targets include important effectors of the Ras pathway and essential genes required for cell division. Together, this study establishes a role for the loss of microRNA-203 in promoting selection and expansion of HRas mutated cells and identifies a mechanism through which microRNA-203 antagonizes HRas-mediated tumorigenesis. Identifying mRNA and microRNA networks regulated by oncogenic HRasG12V in primary keratinocytes through the use of 3Seq and small-RNA-Sequencing. Additionally we utilize ribosome-profiling, 3Seq, Microarray and Ago2-HITS-CLIP approaches to identify novel miR-203 target genes.

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