%0 Journal Article
%T Comprehensive Investigation of miRNome Identifies Novel Candidate miRNA-mRNA Interactions Implicated in T-Cell Acute Lymphoblastic Leukemia
%A Anna Lalik
%A Bronis£¿awa Szarzy¨½ska-Zawadzka
%A Jerzy R. Kowalczyk
%A Krzysztof Ka£¿wak
%A Ludomi£¿a Machowska
%A Marek Ussowicz
%A Maria Kosmalska
%A Ma£¿gorzata Dawidowska
%A Micha£¿ Witt
%A Monika Drobna
%A Monika Lejman
%A Roman Jaksik
%A Tomasz Szczepa¨½ski
%A £¿ukasz S£¿dek
%J Archive of "Neoplasia (New York, N.Y.)".
%D 2019
%R 10.1016/j.neo.2019.01.004
%X 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¨Cmediated 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¡ä 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
%K ALL
%K acute lymphoblastic leukemia
%K EGIL
%K European Group for Immunological Classification of Leukemias
%K GEO
%K Gene Expression Omnibus
%K GO
%K Gene Ontology
%K isomiR
%K isoform of miRNA
%K KEGG
%K Kyoto Encyclopedia of Genes and Genomes
%K miRNome
%K transcriptome of miRNAs
%K MRE
%K miRNA response element
%K OR
%K Odds ratio
%K RT-qPCR
%K quantitative reverse transcription polymerase chain reaction
%K small RNA-seq
%K next-generation sequencing of small RNAs
%K T-ALL
%K T-cell acute lymphoblastic leukemia
%K 3¡äUTR
%K 3¡ä untranslated region
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372882/