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

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

PROVIDER: PRJEB30028 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2938230.fastq.gz	Fastqsanger.gz
	ERR2938240.fastq.gz	Fastqsanger.gz
	ERR2938250.fastq.gz	Fastqsanger.gz
	ERR2938260.fastq.gz	Fastqsanger.gz
	ERR2938231.fastq.gz	Fastqsanger.gz

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

Project description: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).

2019-01-28 | E-MTAB-7446 | biostudies-arrayexpress

Comprehensive Investigation of miRNome Identifies Novel Candidate miRNA-mRNA Interactions Implicated in T-Cell Acute Lymphoblastic Leukemia.

Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we characterized the miRNome of 34 pediatric T-ALL samples, including the expression of isomiRs and the identification of candidate novel miRNAs (not previously annotated in miRBase). For the first time, we show that immunophenotypic subtypes of T-ALL present different miRNA expression profiles. To extend miRNome characteristics in T-ALL (to 82 T-ALL cases), we combined our small RNA-seq results with data available in Gene Expression Omnibus. We report on miRNAs most abundantly expressed in pediatric T-ALL and miRNAs differentially expressed in T-ALL versus normal mature T-lymphocytes and thymocytes, representing candidate oncogenic and tumor suppressor miRNAs. Using eight target prediction algorithms and pathway enrichment analysis, we identified differentially expressed miRNAs and their predicted targets implicated in processes (defined in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of potential importance in pathogenesis of T-ALL, including interleukin-6-mediated signaling, mTOR signaling, and regulation of apoptosis. We finally focused on hsa-mir-106a-363 cluster and functionally validated direct interactions of hsa-miR-20b-5p and hsa-miR-363-3p with 3' untranslated regions of their predicted targets (PTEN, SOS1, LATS2), overrepresented in regulation of apoptosis. hsa-mir-106a-363 is a paralogue of prototypic oncogenic hsa-mir-17-92 cluster with yet unestablished role in the pathogenesis of T-ALL. Our study provides a firm basis and data resource for functional analyses on the role of miRNA-mRNA interactions in T-ALL.

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Project description:Purpose: Cadmium is a nonessential heavy metal and a well known toxic agent. Cadmium is known to alter the gene expression and signaling but the role of miRNAs during Cadmium exposure is not understood. Methods: Mice were treated with 100 mg/ ml cadmium chloride for 120 days and accumulation of cadmium in blood and organs are confirmed by GFAAS. Subsequently, the total RNA was isolated from the whole blood and small RNA sequencing was executed in Illumina HiSeq 1000. Results: The reads were annotated to the mice genome and miRNAs in miRbase using miRDeep* and novel miRNAs were also predicted. The differential expression was studied by DeSeq Conclusions: This is the first report to reveal the cadmium responsive miRNome. These candidate miRNAs can serve as biomarkers for cadmium Whole blood small RNA profiles of control and cadmium exposed mice generated by deep sequencing using Illumina HiSeq 1000

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