Paired miRNA- and messenger RNA-sequencing identifies novel miRNA-mRNA interactions in multiple myeloma.

Autor: Aass KR; Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Gastrosenteret, Prinsesse Kristinas gt. 1, 7491, Trondheim, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, 7491, Trondheim, Norway., Nedal TMV; Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Gastrosenteret, Prinsesse Kristinas gt. 1, 7491, Trondheim, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, 7491, Trondheim, Norway., Tryggestad SS; Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Gastrosenteret, Prinsesse Kristinas gt. 1, 7491, Trondheim, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, 7491, Trondheim, Norway., Haukås E; Department of Hematology, Stavanger University Hospital, 4011, Stavanger, Norway., Slørdahl TS; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, 7491, Trondheim, Norway.; Department of Hematology, St. Olavs University Hospital, 7030, Trondheim, Norway., Waage A; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, 7491, Trondheim, Norway.; Department of Hematology, St. Olavs University Hospital, 7030, Trondheim, Norway., Standal T; Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Gastrosenteret, Prinsesse Kristinas gt. 1, 7491, Trondheim, Norway. therese.standal@ntnu.no.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, 7491, Trondheim, Norway. therese.standal@ntnu.no.; Department of Hematology, St. Olavs University Hospital, 7030, Trondheim, Norway. therese.standal@ntnu.no., Mjelle R; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Erling Skjalgssons gt. 1, 7491, Trondheim, Norway. robin.mjelle@ntnu.no.; Bioinformatics Core Facility - BioCore, Norwegian University of Science and Technology NTNU, 7491, Trondheim, Norway. robin.mjelle@ntnu.no.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jul 15; Vol. 12 (1), pp. 12147. Date of Electronic Publication: 2022 Jul 15.
DOI: 10.1038/s41598-022-16448-0
Abstrakt: Multiple myeloma (MM) is an incurable cancer of terminally differentiated plasma cells that proliferate in the bone marrow. miRNAs are promising biomarkers for risk stratification in MM and several miRNAs are shown to have a function in disease pathogenesis. However, to date, surprisingly few miRNA-mRNA interactions have been described for and functionally validated in MM. In this study, we performed miRNA-seq and mRNA-seq on CD138 + cells isolated from bone marrow aspirates of 86 MM patients to identify novel interactions between sRNAs and mRNAs. We detected 9.8% significantly correlated miRNA-mRNA pairs of which 5.17% were positively correlated and 4.65% were negatively correlated. We found that miRNA-mRNA pairs that were predicted by in silico target-prediction algorithms were more negatively correlated than non-target pairs, indicating functional miRNA targeting and that correlation between miRNAs and mRNAs from patients can be used to identify miRNA-targets. mRNAs for negatively correlated miRNA-mRNA target pairs were associated with gene ontology terms such as autophagy, protein degradation and endoplasmic stress response, reflecting important processes in MM. Targets for two specific miRNAs, miR-125b-5p and miR-365b-3p, were functionally validated in MM cell line transfection experiments followed by RNA-sequencing and qPCR. In summary, we identified functional miRNA-mRNA target pairs by correlating miRNA and mRNA data from primary MM cells. We identified several target pairs that are of potential interest for further studies. The data presented here may serve as a hypothesis-generating knowledge base for other researchers in the miRNA/MM field. We also provide an interactive web application that can be used to exploit the miRNA-target interactions as well as clinical parameters associated to these target-pairs.
(© 2022. The Author(s).)
Databáze: MEDLINE
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