Exosomal miR‐21‐5p derived from bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion by targeting PIK3R1

• Published in: Journal of cellular and molecular medicine 2021-12, Vol.25 (23), p.11016-11030
• Main Authors: Qi, Jin, Zhang, Ruihao, Wang, Yapeng
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Antigens; Bioinformatics; Bone cancer; Bone marrow; Cell culture; Cell growth; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cells, Cultured; Class Ia Phosphatidylinositol 3-Kinase - genetics; Coculture Techniques - methods; Exosomes; Exosomes - genetics; Experiments; Flow cytometry; Gene expression; Humans; Kinases; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Metastasis; Mice; Microenvironments; MicroRNAs - genetics; miR‐21‐5p; Original; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma cells; Paracrine signalling; PI3K/Akt/mTOR pathway; PIK3R1; Pluripotency; Polymerase chain reaction; Reporter gene; Sarcoma; Stem cells; TOR protein; Transcription Factors - genetics; Tumor Microenvironment - genetics; Tumors
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.17024

Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can release a large number of exosomes which act as paracrine mediators in tumour‐associated microenvironment. However, the role of MSC‐derived exosomes in pathogenesis and progression of cancer cells especially osteosarcoma has not been thoroughly clarified until now. In this study, we established a co‐culture model for human bone marrow‐derived MSCs with osteosarcoma cells, then extraction of exosomes from induced MSCs and study the role of MSC‐derived exosomes in the progression of osteosarcoma cell. The aim of this study was to address potential cell biological effects between MSCs and osteosarcoma cells. The results showed that MSC‐derived exosomes can significantly promote osteosarcoma cells’ proliferation and invasion. We also found that miR‐21‐5p was significantly over‐expressed in MSCs and MSC‐derived exosomes by quantitative real‐time polymerase chain reaction (qRT‐PCR), compared with human foetal osteoblastic cells hFOB1.19. MSC‐derived exosomes transfected with miR‐21‐5p could significantly enhance the proliferation and invasion of osteosarcoma cells in vitro and in vivo. Bioinformatics analysis and dual‐luciferase reporter gene assays validated the targeted relationship between exosomal miR‐21‐5p and PIK3R1; we further demonstrated that miR‐21‐5p‐abundant exosomes derived human bone marrow MSCs could activate PI3K/Akt/mTOR pathway by suppressing PIK3R1 expression in osteosarcoma cells. In summary, our study provides new insights into the interaction between human bone marrow MSCs and osteosarcoma cells in tumour‐associated microenvironment.