RESEARCH ARTICLE IL-17/miR-192/IL-17Rs Regulatory Feedback Loop Facilitates Multiple Myeloma Progression

Multiple myeloma (MM) is a clonal plasma cell disorder which constitutes the second most common hematological malignancy, and remains an incurable tumor with poor survival. Recently, interleukin-17 (IL-17), produced locally in the tumor microenvironment, has been reported to play a crucial role in tumor immunity. In this study, we determined that exposure of MM cells to IL-17 had various promotive influences on different aspects of tumor progression. IL-17 significantly induced cell proliferation, inhibited cellular apoptosis, repressed cell adhesion to fibronectin and collagen I, and facilitated cell migration. Exposure to IL-17 also resulted in epithelial-mesenchymal transition (EMT), as evidenced by repression of the epithelial marker E-cadherin, and induction of the mesenchymal marker Vimentin, and EMT transcription factors Snail and Slug. Further experiments showed that IL-17 activated the oncogenic p65 transcription factor, which directly repressed the miR-192 gene via binding to the miR-192 promoter. Loss of miR-192 in MM cells can mimic the effects of IL-17, and was required for the above oncogenic effects o