MicroRNAs regulate key cell survival pathways and mediate chemosensitivity during progression of diffuse large B-cell lymphoma

Blood Cancer Journal
Suvi-Katri LeivonenSirpa Leppä

Abstract

Despite better therapeutic options and improved survival of diffuse large B-cell lymphoma (DLBCL), 30-40% of the patients experience relapse or have primary refractory disease with a dismal prognosis. To identify biological correlates for treatment resistance, we profiled microRNAs (miRNAs) of matched primary and relapsed DLBCL by next-generation sequencing. Altogether 492 miRNAs were expressed in the DLBCL samples. Thirteen miRNAs showed significant differential expression between primary and relapse specimen pairs. Integration of the differentially expressed miRNAs with matched mRNA expression profiles identified highly anti-correlated, putative targets, which were significantly enriched in cancer-associated pathways, including phosphatidylinositol (PI)), mitogen-activated protein kinase (MAPK), and B-cell receptor (BCR) signaling. Expression data suggested activation of these pathways during disease progression, and functional analyses validated that miR-370-3p, miR-381-3p, and miR-409-3p downregulate genes on the PI, MAPK, and BCR signaling pathways, and enhance chemosensitivity of DLBCL cells in vitro. High expression of selected target genes, that is, PIP5K1 and IMPA1, was found to be associated with poor survival in two ...Continue Reading

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Citations

Jul 18, 2020·International Journal of Molecular Sciences·Alex Cleber Improta-CariaBruno Solano de Freitas Souza
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Datasets Mentioned

BETA
GSE69810
GSE10846

Methods Mentioned

BETA
reverse transcription PCR
RNA-seq
Tandem Repeat
PCR

Software Mentioned

DIANA microT
SePIA
Microcosm
SPSS
TargetScan Human
PITA
Cytoscape

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