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

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2021 Feb 10

PMID 33564242

Citations 22

Authors

Fujiang Li

Xin Chen

Cong Shang

Qinglong Ying

Xianjun Zhou

Rongkun Zhu

Hongting Lu

Xiwei Hao

Qian Dong

Zhong Jiang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Significance of exosomes in osteosarcoma research: a systematic review and meta-analysis of a singular clinical investigation.

Liu X, Ye J, Guo W, Wang J Front Cell Dev Biol. 2024; 12:1473044.

PMID: 39605980 PMC: 11599209. DOI: 10.3389/fcell.2024.1473044.

The role of neutrophils in osteosarcoma: insights from laboratory to clinic.

Xia M, Han Y, Sun L, Li D, Zhu C, Li D Front Immunol. 2024; 15:1490712.

PMID: 39582869 PMC: 11582048. DOI: 10.3389/fimmu.2024.1490712.

Exosomes Derived from Runx2-Overexpressing BMSCs Enhance Cartilage Tissue Regeneration and Prevent Osteoarthritis of the Knee in a Rabbit Model.

Hu J, Shi Z, Liu X, Cai H, Yang A, Sun D Stem Cells Int. 2024; 2022:6865041.

PMID: 39282499 PMC: 11401735. DOI: 10.1155/2022/6865041.

Osteosarcoma in a ceRNET perspective.

Mosca N, Alessio N, Di Paola A, Marrapodi M, Galderisi U, Russo A J Biomed Sci. 2024; 31(1):59.

PMID: 38835012 PMC: 11151680. DOI: 10.1186/s12929-024-01049-y.

Exploring the Impact of Exosomal Cargos on Osteosarcoma Progression: Insights into Therapeutic Potential.

Chen C, Benavente C Int J Mol Sci. 2024; 25(1).

PMID: 38203737 PMC: 10779183. DOI: 10.3390/ijms25010568.

References

Barile L, Vassalli G . Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol Ther. 2017; 174:63-78. DOI: 10.1016/j.pharmthera.2017.02.020. View

Chen Y, Huang W, Sun W, Zheng B, Wang C, Luo Z . LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway. Cell Physiol Biochem. 2018; 51(3):1313-1326. DOI: 10.1159/000495550. View

Smolle M, Pichler M . The Role of Long Non-Coding RNAs in Osteosarcoma. Noncoding RNA. 2018; 4(1). PMC: 5890394. DOI: 10.3390/ncrna4010007. View

Wang Y, Chu Y, Li K, Zhang G, Guo Z, Wu X . Exosomes Secreted by Adipose-Derived Mesenchymal Stem Cells Foster Metastasis and Osteosarcoma Proliferation by Increasing COLGALT2 Expression. Front Cell Dev Biol. 2020; 8:353. PMC: 7262406. DOI: 10.3389/fcell.2020.00353. View

Ren F, Zhang W, Lu S, Ren H, Guo Y . NRSN2 promotes breast cancer metastasis by activating PI3K/AKT/mTOR and NF-κB signaling pathways. Oncol Lett. 2019; 19(1):813-823. PMC: 6924201. DOI: 10.3892/ol.2019.11152. View

Arun G, Spector D . MALAT1 long non-coding RNA and breast cancer. RNA Biol. 2019; 16(6):860-863. PMC: 6546402. DOI: 10.1080/15476286.2019.1592072. View

Yang X, Yang J, Lei P, Wen T . LncRNA MALAT1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microRNA-34c/SATB2 axis. Aging (Albany NY). 2019; 11(20):8777-8791. PMC: 6834402. DOI: 10.18632/aging.102264. View

Wang J, Liu S, Shi J, Li J, Wang S, Liu H . The Role of miRNA in the Diagnosis, Prognosis, and Treatment of Osteosarcoma. Cancer Biother Radiopharm. 2019; 34(10):605-613. DOI: 10.1089/cbr.2019.2939. View

Tang W, Ren A, Xiao H, Sun H, Li B . Highly expressed NRSN2 is related to malignant phenotype in ovarian cancer. Biomed Pharmacother. 2016; 85:248-255. DOI: 10.1016/j.biopha.2016.11.012. View

10.

Yan L, Wu X, Liu Y, Xian W . LncRNA Linc00511 promotes osteosarcoma cell proliferation and migration through sponging miR-765. J Cell Biochem. 2018; 120(5):7248-7256. DOI: 10.1002/jcb.27999. View

11.

Keremu A, Maimaiti X, Aimaiti A, Yushan M, Alike Y, Yilihamu Y . NRSN2 promotes osteosarcoma cell proliferation and growth through PI3K/Akt/MTOR and Wnt/β-catenin signaling. Am J Cancer Res. 2017; 7(3):565-573. PMC: 5385644. View

12.

Kong G, Qi X, Wang J . Effect of lncRNA LET on proliferation and invasion of osteosarcoma cells. Eur Rev Med Pharmacol Sci. 2018; 22(6):1609-1614. DOI: 10.26355/eurrev_201803_14567. View

13.

Qin F, Tang H, Zhang Y, Zhang Z, Huang P, Zhu J . Bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-208a promotes osteosarcoma cell proliferation, migration, and invasion. J Cell Physiol. 2019; 235(5):4734-4745. DOI: 10.1002/jcp.29351. View

14.

Simpson E, Brown H . Understanding osteosarcomas. JAAPA. 2018; 31(8):15-19. DOI: 10.1097/01.JAA.0000541477.24116.8d. View

15.

Mulcahy L, Pink R, Carter D . Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014; 3. PMC: 4122821. DOI: 10.3402/jev.v3.24641. View

16.

Zhang X, Hamblin M, Yin K . The long noncoding RNA Malat1: Its physiological and pathophysiological functions. RNA Biol. 2017; 14(12):1705-1714. PMC: 5731810. DOI: 10.1080/15476286.2017.1358347. View

17.

Sun Y, Huo C, Qiao Z, Shang Z, Uzzaman A, Liu S . Comparative Proteomic Analysis of Exosomes and Microvesicles in Human Saliva for Lung Cancer. J Proteome Res. 2018; 17(3):1101-1107. DOI: 10.1021/acs.jproteome.7b00770. View

18.

Kager L, Tamamyan G, Bielack S . Novel insights and therapeutic interventions for pediatric osteosarcoma. Future Oncol. 2016; 13(4):357-368. DOI: 10.2217/fon-2016-0261. View

19.

Xu R, Rai A, Chen M, Suwakulsiri W, Greening D, Simpson R . Extracellular vesicles in cancer - implications for future improvements in cancer care. Nat Rev Clin Oncol. 2018; 15(10):617-638. DOI: 10.1038/s41571-018-0036-9. View

20.

Hou Y, Feng H, Jiao J, Qian L, Sun B, Chen P . Mechanism of miR-143-3p inhibiting proliferation, migration and invasion of osteosarcoma cells by targeting MAPK7. Artif Cells Nanomed Biotechnol. 2019; 47(1):2065-2071. DOI: 10.1080/21691401.2019.1620252. View