Pluto Bioinformatics

GSE153287: Transcriptional changes induced by miR-21 antagonism in T helper cells abrogates Th17 tumor promoting functions

Bulk RNA sequencing

Multiple myeloma (MM) is a hematologic malignancy tightly dependent on inflammatory bone marrow microenvironment. IL-17 producing CD4+ T cells (Th17) sustain MM cells growth and osteclast-dependent bone damage. In turn, Th17 generation and function rely on inflammatory stimuli. There is compelling evidence that miR-21 is involved in Th17 differentiation and effector functions. Here, we investigated the role of miR-21, which is an inflammation induced miRNA, in Th17-mediated MM tumor growth and bone disease. We found that inhibition of miR-21 in naive T cells (miR-21i-T cells) impaired differentiation towards Th17 in vitro. Analysis of miR-21-related molecular pathways in Th17 cells demonstrated upregulation of STAT-1/-5a-5b, downregulation of STAT-3 and redirection of Th17 to Th1/activated like cells as shown by a pair-to-pair RNAseq and proteome/phosphoproteome analysis. Inhibition of miR-21 impaired Th17 mediated MM cell proliferation and osteoclast activity in vitro. We recapitulated and validated these findings in NOD/SCID gNULL mice, injected intratibially with miR-21i-T cells and MM cells. Our findings disclose the critical involvement of miR-21 in pathogenic Th17 development and activity and open the avenue to the design of miR-21-targeting strategies to counteract microenviromental dependence of MM growth and bone disease. SOURCE: Cirino Botta ( - "Annunziata" Hospital of Cosenza

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