Abstract
Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro. We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy.
Highlights
Multiple myeloma (MM) is the second most common hematological malignancy after non-Hodgkin lymphoma (Siegel et al, 2021)
Osteogenesis induction results showed that primary cultured Bone marrow-derived mesenchymal stem cell (BMSC) formed small lamellar mineralized nodules after 21 days of culture, but the bone nodules from benign diseases (BD)-MSCs were darker and larger in appearance compared to those from MM-MSCs (Figure 1D)
These results suggested that miR-483-5p/tissue inhibitor of metalloproteinase 2 (TIMP2) axis may play a vital role in MM (Figure 6)
Summary
Multiple myeloma (MM) is the second most common hematological malignancy after non-Hodgkin lymphoma (Siegel et al, 2021). MM is a diffuse neoplasm of bone marrow B cell-derived plasma cells (PCs) and the malignant cells mingle with the hematopoietic cells throughout the bone marrow (BM) (Palumbo and Anderson, 2011). Though emerging therapies such as immunotherapy and targeted therapeutics have evolved, MM remains an incurable disease and causes end-organ damage, including hypercalcemia, renal impairment, anemia and bone lesions (Shah and Mailankody, 2020). BMSCs play an essential role in the malignant progression of hematologic diseases, including MM
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