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http://dx.doi.org/10.7314/APJCP.2015.16.10.4203

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation  

Wang, Jian-Jun (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University)
Wang, Ze-You (Department of Clinical Laboratory, The Second Xiangya Hospital of Central South University)
Chen, Rui (Department of Pathology, Chongqing Cancer Institute)
Xiong, Jing (Department of Ophthalmology, Xiangya Hospital, Central South University)
Yao, Yong-Liang (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University)
Wu, Jian-Hong (Department of Clinical Laboratory, Kunshan First People's Hospital, Affiliated to JiangSu University)
Li, Guang-Xin (Department of Pathology, Chongqing Cancer Institute)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.10, 2015 , pp. 4203-4209 More about this Journal
Abstract
Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.
Keywords
Exosomes; gastric cancer; miR-21; macrophages;
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1 Alvarez-Erviti L, Seow Y, Yin H, et al (2011). Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol, 29, 341-5.   DOI   ScienceOn
2 Bartel DP (2009). MicroRNAs: Target recognition and regulatory functions. Cell, 136, 215-33.   DOI
3 Chen CY, Hogan MC, Ward CJ (2013). Purification of exosomelike vesicles from urine. Methods Enzymol, 524, 225-41.   DOI
4 Chen WX, Cai YQ, Lv MM, et al (2014). Exosomes from docetaxel-resistant breast cancer cells alter chemosensitivity by delivering microRNAs. Tumour Biol, 35, 9649-59.   DOI
5 Cui L, Zhang X, Ye G, et al (2013). Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer. Cancer, 119, 1618-26.   DOI
6 Delcayre, A, L. Pecq, JB (2006). Exosomes as novel therapeutic nanodevices. Curr Opin Mol Ther, 8, 31-8.
7 Du L, Pertsemlidis A (2012). MicroRNA regulation of cell viability and drug sensitivity in lung cancer. Expert Opin Biol Ther, 12, 1221-39.   DOI   ScienceOn
8 Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.   DOI
9 Guo J, Miao Y, Xiao B, et al (2009). Differential expression of microRNA species in human gastric cancer versus nontumorous tissues. J Gastroenterol Hepatol, 24, 652-7.   DOI   ScienceOn
10 He L, Hannon GJ (2004). MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet, 5, 522-31.   DOI
11 Hood JL, Wickline SA (2012). A systematic approach to exosome-based translational, nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 4, 458-67.   DOI
12 Hu G, Gong AY, Roth AL, et al (2013). Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense. PLoS Pathog, 9, 1003261.   DOI
13 Hu H, Li Y, Gu J, et al (2010). Antisense oligonucleotide against miR-21 inhibits migration and induces apoptosis in leukemic K562 cells. Leuk Lymphoma, 51, 694-701.   DOI   ScienceOn
14 Konishi H, Ichikawa D, Komatsu S, et al (2012). Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma. Br J Cancer, 106, 740-7.   DOI   ScienceOn
15 Huang Y, Yang YB, Zhang XH, et al (2013). MicroRNA-21 gene and cancer. Med Oncol, 30, 376-8.   DOI
16 Izquierdo-Useros N, Naranjo-Gómez M, Erkizia I, et al (2010). HIV and mature dendritic cells: Trojan exosomes riding the Trojan horse? PLoS Pathog, 6, 1000740.   DOI
17 Keller S, Ridinger J, Rupp AK, et al (2011). Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med, 9, 86.   DOI
18 Kooijmans SA, Vader P, van Dommelen SM, et al (2012). Exosome mimetics: a novel class of drug delivery systems. Int J Nanomedicine, 7, 1525-41.
19 Li SC, Liao YL, Ho MR, et al (2012). miRNA arm selection and isomiR distribution in gastric cancer. BMC Genomics, 1, 13.
20 Liu H (2012) MicroRNAs in breast cancer initiation and progression. Cell Mol Life Sci, 69, 3587-99.   DOI
21 Marcus ME, Leonard JN (2013). Fed exosomes: engineering therapeutic biological nanoparticles that truly deliver. Pharmaceuticals, 6, 659-80.   DOI
22 McDonald MK, Tian Y, Qureshi RA, et al (2014). Functional significance of macrophage-derived exosomes in inflammation and pain. Pain, 155, 1527-39.   DOI
23 Menendez P, Villarejo P, Padilla D, et al (2013). Diagnostic and prognostic significance of serum microRNAs in colorectal cancer. J Surg Oncol, 107, 217-20.   DOI   ScienceOn
24 Mu W, Rana S, Zöller M (2013). Host matrix modulation by tumor exosomespromotes motility and invasiveness. Neoplasia, 15, 875-87.   DOI
25 Segura E, Guerin C, Hogg N, et al (2007). CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. J Immunol, 179, 1489-96   DOI
26 Peinado H, Aleckovic M, Lavotshkin S, et al (2012). Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med, 18, 883-91.   DOI   ScienceOn
27 Ramakrishnaiah V, Thumann C, Fofana I, et al (2013). Exosomemediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc Natl Acad Sci USA, 110, 13109-13.   DOI
28 Saeki N, Ono H, Sakamoto H, et al (2013). Genetic factors related to gastric cancer susceptibility identified using a genomewide association study. Cancer Sci, 104, 1-8.   DOI   ScienceOn
29 Seow Y, Wood MJ (2009). Biological gene delivery vehicles: d. Mol Ther, 17, 767-77.   DOI
30 Torregrosa PP, Esser J, Admyre C, et al (2012). Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma. Allergy, 67, 911-9   DOI
31 Vaksman O, Trope C, Davidson B, et al (2014). Exosomederived miRNAs and ovarian carcinoma progression. Carcinogenesis, 35, 2113-20.   DOI
32 Vlassov AV, Magdaleno S, Setterquist R, et al (2012). Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta, 1820, 940-8.   DOI   ScienceOn
33 Wahlgren J, De L Karlson T, Brisslert M, et al (2012). Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res, 40, 130.
34 Yamada T, Inoshima Y, Matsuda T, et al (2012). Comparison of methods for isolating exosomes from bovine milk. J Vet Med Sci,74, 1523-5.   DOI
35 Whiteside TL, Mandapathil M, Szczepanski M, et al (2011). Mechanisms of tumor escape from the immune system: adenosine-producing Treg, exosomes and tumor-associated TLRs. Bull Cancer, 98, 25-31.
36 Wu JH, Yao YL, Gu T, et al (2014). MiR-421 regulates the apoptosis of BGC-823 gastric cancer cells by targeting caspase-3. Asian Pac J Cancer Prev, 15, 5463-8.   DOI   ScienceOn
37 Xu Y, Luo F, Liu Y, et al (2014). Exosomal miR-21 derived from arsenite-transformed human bronchial epithelial cells promotes cell proliferation associated with arsenite carcinogenesis. Arch Toxicol, [Epub ahead of print].
38 Yang L (2006). Incidence and mortality of gastric cancer in China. World J Gastroenterol, 12, 17-20.   DOI
39 Zech D, Rana S, Buchler MW, et al (2012). Tumor-exosomes and leukocyte activation: an ambivalent crosstalk. Cell Commun Signal, 10, 37.   DOI
40 Zeng Y, Wagner EJ, Cullen BR (2002). Both natural and designed microRNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Mol Cell, 9, 1327-33.   DOI
41 Zhang J, Yang Y, Liu Y,et al (20134). MicroRNA-21 regulates biological behaviors in papillary thyroid carcinoma by targeting programmed cell death 4. J Surg Res, 189, 68-74.
42 Zhuang X, Xiang X, Grizzle W, et al (2011). Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther, 19, 1769-79.   DOI