Functional role of the miR-24-1 cluster in IL-6- and APRIL-dependent survival of plasma cells

• Applicant: Dr. Melanie Abram
• Subject Area: Immunology
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 281487682

At that time, plasma cell-triggered chronic inflammations as well as plasma cell malignancies still remain a clinical problem, because of the long-term survival of pathogenic plasma cells in their survival niches. Plasma cell survival is a complex process which depends both on extracellular survival factors as well as intracellular effectors that regulate cell homeostasis. The cytokines APRIL and IL-6 represent prominent plasma cell survival factors, and IL-6 is also an effective mediator of chronic inflammatory processes. In our preliminary work, we could show a direct connection between a small, non-coding RNA, the miR-24-3p, and IL-6-dependent survival of human plasma cells. Furthermore, there seems a direct impact of IL-6 and APRIL on the expression level of miR-24-3p and the adjacent miRNAs miR-27b-3p and miR-23b-3p, which all build together the miR-24-1 cluster on chromosome 9. Our aim is to discover how miR-24-1 cluster genes are regulated by IL-6 and APRIL, and how these miRNAs intervene in plasma cell function, particularly their survival. For that, we will induce knockdown or overexpression of the miR-24-1 cluster genes in IL-6 and APRIL-induced plasma cell survival, combined with target gene analysis. Furthermore, the role of the miR-24-1 cluster in vivo will be analyzed by using a mouse model of multiple myeloma. Our results could provide new opportunities for the treatment of plasma cell-mediated disease.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Rudolf Manz