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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Suvi-Katri Leivonen, Katherine Icay, Kirsi Jäntti, Ilari Siren, Chengyu Liu, Amjad Alkodsi, Alejandra Cervera, Maja Ludvigsen, Stephen Jacques Hamilton-Dutoit, Francesco d’Amore, Marja-Liisa Karjalainen-Lindsberg, Jan Delabie, Harald Holte, Rainer Lehtonen, Sampsa Hautaniemi, Sirpa 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 independent cohorts of chemoimmunotherapy-treated patients (n = 92 and n = 233). Taken together, our results demonstrate that differentially expressed miRNAs contribute to disease progression by regulating key cell survival pathways and by mediating chemosensitivity, thus representing potential novel therapeutic targets. More... »

PAGES

654

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41408-017-0033-8

    DOI

    http://dx.doi.org/10.1038/s41408-017-0033-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1099663742

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29242506


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