Author:
Miaomiao Sun,Xiaoqian Wang,Yuwei Shou,Chao Chen,Chenbo Yang,Yinghao Liang,Yichen Hong,Jiao Shu,Kuisheng Chen
Abstract
AbstractMultiple myeloma (MM) is the second most common hematological malignancy, and angiogenesis determines its progression. In the tumor microenvironment, normal fibroblasts (NFs) are transformed into cancer-associated fibroblasts (CAFs), which can promote angiogenesis. Microribonucleic acid-21 (miR-21) is highly expressed in various tumors. However, research on the relationship between tumor angiogenesis and miR-21 is rare. We analyzed the relationship between miR-21, CAFs, and angiogenesis in MM. NFs and CAFs were isolated from the bone marrow fluids of patients with dystrophic anemia and newly-diagnosed MM. Co-culturing of CAF exosomes with multiple myeloma endothelial cells (MMECs) showed that CAF exosomes were able to enter MMECs in a time-dependent manner and initiate angiogenesis by promoting proliferation, migration, and tubulogenesis. We found that miR-21 was abundant in CAF exosomes, entering MMECs and regulating angiogenesis in MM. By transfecting NFs with mimic NC, miR-21 mimic, inhibitor NC, and miR-21 inhibitor, we found that miR-21 significantly increased the expression of alpha-smooth muscle actin and fibroblast activation protein in NFs. Our results showed that miR-21 can transform NFs into CAFs, and that CAF exosomes promote angiogenesis by carrying miR-21 into MMECs. Therefore, CAF-derived exosomal miR-21 may serve as a novel diagnostic biomarker and therapeutic target for MM.
Funder
National Natural Science Foundation of China
Young and middle-aged health science and technology innovation leading talents in Henan Province
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献