Cancer-associated fibroblast-derived exosome microRNA-21 promotes angiogenesis in multiple myeloma.
Autor: | Miaomiao S; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.; BGI College, Zhengzhou University, Zhengzhou, People's Republic of China.; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Xiaoqian W; BGI College, Zhengzhou University, Zhengzhou, People's Republic of China.; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Yuwei S; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Chao C; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Chenbo Y; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Yinghao L; BGI College, Zhengzhou University, Zhengzhou, People's Republic of China.; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Yichen H; BGI College, Zhengzhou University, Zhengzhou, People's Republic of China.; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Jiao S; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China., Kuisheng C; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China. chenksh2002@163.com.; Henan Province Key Laboratory of Tumor Pathology, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China. chenksh2002@163.com. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2023 Jun 14; Vol. 13 (1), pp. 9671. Date of Electronic Publication: 2023 Jun 14. |
DOI: | 10.1038/s41598-023-36092-6 |
Abstrakt: | Multiple 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. (© 2023. The Author(s).) |
Databáze: | MEDLINE |
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