Exosomes MiR-22-3p Derived from Mesenchymal Stem Cells Suppress Colorectal Cancer Cell Proliferation and Invasion by Regulating RAP2B and PI3K/AKT Pathway

Overview

Journal J Oncol

Specialty Oncology

Date 2021 Jul 9

PMID 34239562

Citations 32

Authors

Yan Wang

Changkun Lin

Affiliations

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Abstract

Objective: Exosomes (exo) which contain proteins, microRNAs (miRNAs), and other bioactive substances can participate in intercellular signal transduction and material transport. Bone marrow mesenchymal stem cells (BMSCs) have a strong ability to produce exosomes. The purpose of this study was to observe the effect of hBMSCs-derived-exo miR-22-3p on proliferation and invasion of colorectal cancer (CRC) cells and to explore its mechanism.

Methods: miR-22-3p and RAS oncogene family (RAP2B) expression was detected using qRT-PCR or Western blotting. Their interaction was confirmed by dual luciferase activity assay. Effects of miR-22-3p on cell proliferation and invasion were evaluated by CCK-8 and Transwell assay, respectively. Exosomes were extracted by the ultracentrifugation and identified through electron microscopy and Western blotting.

Results: In CRC tissues and cells, downregulation of miR-22-3p and upregulation of RAP2B were observed. According to the analysis of dual luciferase activity, RAP2B was a target gene of miR-22-3p. In addition, miR-22-3p obviously repressed the cells proliferation and invasion via mediating RAP2B/PI3K/AKT pathway. Coculture experiments indicated that miR-22-3p derived from hBMSCs-exo had inhibition effects on SW480 cell proliferation and invasion.

Conclusions: Collectively, miR-22-3p from hBMSCs-exo might impede CRC progression, which emphasized the potential of hBMSCs-exo-miR-22-3p as CRC treatment in the future.

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References

Chen H, Li J, Jiang F, Shi W, Chang G . MicroRNA-4461 derived from bone marrow mesenchymal stem cell exosomes inhibits tumorigenesis by downregulating COPB2 expression in colorectal cancer. Biosci Biotechnol Biochem. 2019; 84(2):338-346. DOI: 10.1080/09168451.2019.1677452. View

Shen L, Li Q, Wang W, Zhu L, Zhao Q, Nie Y . Treatment patterns and direct medical costs of metastatic colorectal cancer patients: a retrospective study of electronic medical records from urban China. J Med Econ. 2020; 23(5):456-463. DOI: 10.1080/13696998.2020.1717500. View

Zhang H, Grizzle W . Exosomes and cancer: a newly described pathway of immune suppression. Clin Cancer Res. 2011; 17(5):959-64. PMC: 3155407. DOI: 10.1158/1078-0432.CCR-10-1489. View

Hong S . Genetic and epigenetic alterations of colorectal cancer. Intest Res. 2018; 16(3):327-337. PMC: 6077299. DOI: 10.5217/ir.2018.16.3.327. View

Barcellos-de-Souza P, Gori V, Bambi F, Chiarugi P . Tumor microenvironment: bone marrow-mesenchymal stem cells as key players. Biochim Biophys Acta. 2013; 1836(2):321-35. DOI: 10.1016/j.bbcan.2013.10.004. View

Marley A, Nan H . Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016; 7(3):105-114. PMC: 5069274. View

Yu B, Zhang X, Li X . Exosomes derived from mesenchymal stem cells. Int J Mol Sci. 2014; 15(3):4142-57. PMC: 3975389. DOI: 10.3390/ijms15034142. View

Zhang G, Xia S, Tian H, Liu Z, Zhou T . Clinical significance of miR-22 expression in patients with colorectal cancer. Med Oncol. 2012; 29(5):3108-12. DOI: 10.1007/s12032-012-0233-9. View

Pegtel D, Gould S . Exosomes. Annu Rev Biochem. 2019; 88:487-514. DOI: 10.1146/annurev-biochem-013118-111902. View

10.

Wen D, Zou W, Wen X, Yang Y, Chen Y, He Y . Urban-rural disparity in colorectal cancer incidence and increasing trend in relation to socioeconomic development and urbanization in China. J Int Med Res. 2018; 46(10):4181-4196. PMC: 6166325. DOI: 10.1177/0300060518791090. View

11.

Tomasetti M, Lee W, Santarelli L, Neuzil J . Exosome-derived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy. Exp Mol Med. 2017; 49(1):e285. PMC: 5291842. DOI: 10.1038/emm.2016.153. View

12.

Shirafkan N, Mansoori B, Mohammadi A, Shomali N, Ghasbi M, Baradaran B . MicroRNAs as novel biomarkers for colorectal cancer: New outlooks. Biomed Pharmacother. 2017; 97:1319-1330. DOI: 10.1016/j.biopha.2017.11.046. View

13.

Bergfeld S, DeClerck Y . Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev. 2010; 29(2):249-61. DOI: 10.1007/s10555-010-9222-7. View

14.

Xu Y, Shen L, Li F, Yang J, Wan X, OuYang M . microRNA-16-5p-containing exosomes derived from bone marrow-derived mesenchymal stem cells inhibit proliferation, migration, and invasion, while promoting apoptosis of colorectal cancer cells by downregulating ITGA2. J Cell Physiol. 2019; 234(11):21380-21394. DOI: 10.1002/jcp.28747. View

15.

Jin Y, Yu L, Zhang B, Liu C, Chen Y . Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge. Braz J Med Biol Res. 2018; 51(12):e7811. PMC: 6233523. DOI: 10.1590/1414-431X20187811. View

16.

Zhang X, He Y, Lee K, Dubois W, Li Z, Wu X . Rap2b, a novel p53 target, regulates p53-mediated pro-survival function. Cell Cycle. 2013; 12(8):1279-91. PMC: 3674092. DOI: 10.4161/cc.24364. View

17.

Zhang L, Duan H, Yang Y . Knockdown of Rap2B Inhibits the Proliferation and Invasion in Hepatocellular Carcinoma Cells. Oncol Res. 2017; 25(1):19-27. PMC: 7840814. DOI: 10.3727/096504016X14685034103914. View

18.

Mousavi S, Moallem R, Hassanian S, Sadeghzade M, Mardani R, Ferns G . Tumor-derived exosomes: Potential biomarkers and therapeutic target in the treatment of colorectal cancer. J Cell Physiol. 2019; 234(8):12422-12432. DOI: 10.1002/jcp.28080. View

19.

Corsini E, Mitchell K, Mehran R, Rice D, Sepesi B, Walsh G . Colorectal cancer mutations are associated with survival and recurrence after pulmonary metastasectomy. J Surg Oncol. 2019; 120(4):729-735. DOI: 10.1002/jso.25630. View

20.

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View