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Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/β-Catenin Axis

Authors Li F, Chen X, Shang C, Ying Q, Zhou X, Zhu R, Lu H, Hao X, Dong Q, Jiang Z

Received 22 September 2020

Accepted for publication 25 December 2020

Published 2 February 2021 Volume 2021:14 Pages 737—749

DOI https://doi.org/10.2147/OTT.S283459

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Nicola Silvestris


Fujiang Li, Xin Chen, Cong Shang, Qinglong Ying, Xianjun Zhou, Rongkun Zhu, Hongting Lu, Xiwei Hao, Qian Dong, Zhong Jiang

Department of Pediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People’s Republic of China

Correspondence: Zhong Jiang
Department of Pediatric Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, Shandong, People’s Republic of China
Tel +86 532-82911333
Email jiangzhongqd@126.com

Introduction: Osteosarcoma is a malignant primary bone tumor. Bone marrow-derived mesenchymal stem cells-derived extracellular vesicles (BMSC-EVs) bear repair function for bone and cartilage. This study investigated the mechanism of BMSC-EVs in osteosarcoma cell proliferation, migration and invasion.
Methods: BMSC-EVs were isolated and identified. The effects of different concentrations of EVs on osteosarcoma cell proliferation, migration and invasion were evaluated. LncRNA MALAT1 expression in osteosarcoma cells was detected. BMSCs were transfected with si-MALAT1 or si-NC. The binding relationships between MALAT1 and miR-143, and miR-143 and NRSN2 were verified. Levels of NRSN2 and Wnt/β-catenin pathway key proteins were detected. miR-143 mimic was transfected into EVs-treated osteosarcoma cells. Nude mice were injected with MG63 cells to verify the effect of EVs on osteosarcoma growth in vivo.
Results: BMSC-EVs facilitated proliferation, invasion and migration of osteosarcoma cells. BMSC-EVs carried MALAT1 into osteosarcoma cells. BMSC-EVs-treated osteosarcoma cells showed increased MALAT1 and NRSN2 expressions, decreased miR-143 expression, and activated Wnt/β-catenin pathway. miR-143 mimic or si-MALAT1 reversed the effects of BMSC-EVs on osteosarcoma cells. In vivo experiment confirmed that BMSC-EVs promoted tumor growth in nude mice.
Discussion: BMSC-EVs promoted proliferation, invasion and migration of osteosarcoma cells via the MALAT1/miR-143/NRSN2/Wnt/β-catenin axis. This study might offer new insights into osteosarcoma management.

Keywords: osteosarcoma, bone marrow-derived mesenchymal stem cells, extracellular vesicles, lncRNA MALAT1, miR-143, NRSN2, Wnt/β-catenin pathway

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