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Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Prostate Cancer | Research

Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2

Authors: Shuangjian Jiang, Chengqiang Mo, Shengjie Guo, Jintao Zhuang, Bin Huang, Xiaopeng Mao

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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Abstract

Background

Human bone marrow mesenchymal stem cells (hBMSCs) are implicated in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the physiological mechanisms by which exosomal miR-205 derived from hBMSCs may modulate the growth of prostate cancer cells.

Methods

Microarray-based gene expression profiling of prostate cancer was adopted to identify differentially expressed genes and regulatory miRNAs, which identified the candidates RHPN2 and miR-205 as the study focus. Then the binding affinity between miR-205 and RHPN2 was identified using in silico analysis and luciferase activity detection. Prostate cancer cells were co-cultured with exosomes derived from hBMSCs treated with either miR-205 mimic or miR-205 inhibitor. Subsequently, prostate cancer cell proliferation, invasion, migration, and apoptosis were detected in vitro. The effects of hBMSCs-miR-205 on tumor growth were investigated in vivo.

Results

miR-205 was downregulated, while RHPN2 was upregulated in prostate cancer cells. RHPN2 was a target of miR-205, and upregulated miR-205 inhibited prostate cancer cell proliferation, invasion, and migration and promoted apoptosis by targeting RHPN2. Next, experiments demonstrated that hBMSCs-derived exosomes carrying miR-205 contributed to repressed prostate cancer cell proliferation, invasion, and migration and enhanced apoptosis. Furthermore, in vivo assays confirmed the inhibitory effects of hBMSCs-derived exosomal miR-205 on prostate cancer.

Conclusion

The hBMSCs-derived exosomal miR-205 retards prostate cancer progression by inhibiting RHPN2, suggesting that miR-205 may present a predictor and potential therapeutic target for prostate cancer.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012. Int J Cancer. 2015;136(5):E359–86.CrossRef Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012. Int J Cancer. 2015;136(5):E359–86.CrossRef
2.
go back to reference Pernar CH, Ebot EM, Wilson KM, Mucci LA. The epidemiology of prostate cancer. Cold Spring Harb Perspect Med. 2018;8(12):a030361.CrossRef Pernar CH, Ebot EM, Wilson KM, Mucci LA. The epidemiology of prostate cancer. Cold Spring Harb Perspect Med. 2018;8(12):a030361.CrossRef
3.
go back to reference Attard G, Parker C, Eeles RA, Schroder F, Tomlins SA, Tannock I, et al. Prostate cancer. Lancet. 2016;387(10013):70–82.CrossRef Attard G, Parker C, Eeles RA, Schroder F, Tomlins SA, Tannock I, et al. Prostate cancer. Lancet. 2016;387(10013):70–82.CrossRef
4.
go back to reference Misawa A, Takayama KI, Inoue S. Long non-coding rnas and prostate cancer. Cancer Sci. 2017;108(11):2107–14.CrossRef Misawa A, Takayama KI, Inoue S. Long non-coding rnas and prostate cancer. Cancer Sci. 2017;108(11):2107–14.CrossRef
5.
go back to reference Bergfeld SA, DeClerck YA. Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev. 2010;29(2):249–61.CrossRef Bergfeld SA, DeClerck YA. Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev. 2010;29(2):249–61.CrossRef
6.
go back to reference Ye H, Cheng J, Tang Y, Liu Z, Xu C, Liu Y, et al. Human bone marrow-derived mesenchymal stem cells produced tgfbeta contributes to progression and metastasis of prostate cancer. Cancer Invest. 2012;30(7):513–8.CrossRef Ye H, Cheng J, Tang Y, Liu Z, Xu C, Liu Y, et al. Human bone marrow-derived mesenchymal stem cells produced tgfbeta contributes to progression and metastasis of prostate cancer. Cancer Invest. 2012;30(7):513–8.CrossRef
7.
go back to reference Zhang T, Lee YW, Rui YF, Cheng TY, Jiang XH, Li G. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res Ther. 2013;4(3):70.CrossRef Zhang T, Lee YW, Rui YF, Cheng TY, Jiang XH, Li G. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res Ther. 2013;4(3):70.CrossRef
8.
go back to reference Zhu W, Huang L, Li Y, Zhang X, Gu J, Yan Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012;315(1):28–37.CrossRef Zhu W, Huang L, Li Y, Zhang X, Gu J, Yan Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012;315(1):28–37.CrossRef
9.
go back to reference Arscott WT, Tandle AT, Zhao S, Shabason JE, Gordon IK, Schlaff CD, et al. Ionizing radiation and glioblastoma exosomes: implications in tumor biology and cell migration. Transl Oncol. 2013;6(6):638–48.CrossRef Arscott WT, Tandle AT, Zhao S, Shabason JE, Gordon IK, Schlaff CD, et al. Ionizing radiation and glioblastoma exosomes: implications in tumor biology and cell migration. Transl Oncol. 2013;6(6):638–48.CrossRef
10.
go back to reference Duijvesz D, Luider T, Bangma CH, Jenster G. Exosomes as biomarker treasure chests for prostate cancer. Eur Urol. 2011;59(5):823–31.CrossRef Duijvesz D, Luider T, Bangma CH, Jenster G. Exosomes as biomarker treasure chests for prostate cancer. Eur Urol. 2011;59(5):823–31.CrossRef
11.
go back to reference Lasser C. Exosomal rna as biomarkers and the therapeutic potential of exosome vectors. Expert Opin Biol Ther. 2012;12(Suppl 1):S189–97.CrossRef Lasser C. Exosomal rna as biomarkers and the therapeutic potential of exosome vectors. Expert Opin Biol Ther. 2012;12(Suppl 1):S189–97.CrossRef
12.
go back to reference Kim WT, Kim WJ. Micrornas in prostate cancer. Prostate Int. 2013;1(1):3–9.CrossRef Kim WT, Kim WJ. Micrornas in prostate cancer. Prostate Int. 2013;1(1):3–9.CrossRef
13.
go back to reference Zhang W, Zang J, Jing X, Sun Z, Yan W, Yang D, et al. Identification of candidate mirna biomarkers from mirna regulatory network with application to prostate cancer. J Transl Med. 2014;12:66.CrossRef Zhang W, Zang J, Jing X, Sun Z, Yan W, Yang D, et al. Identification of candidate mirna biomarkers from mirna regulatory network with application to prostate cancer. J Transl Med. 2014;12:66.CrossRef
14.
go back to reference Hessvik NP, Sandvig K, Llorente A. Exosomal mirnas as biomarkers for prostate cancer. Front Genet. 2013;4:36.CrossRef Hessvik NP, Sandvig K, Llorente A. Exosomal mirnas as biomarkers for prostate cancer. Front Genet. 2013;4:36.CrossRef
15.
go back to reference Li J, Yang X, Guan H, Mizokami A, Keller ET, Xu X, et al. Exosome-derived micrornas contribute to prostate cancer chemoresistance. Int J Oncol. 2016;49(2):838–46.CrossRef Li J, Yang X, Guan H, Mizokami A, Keller ET, Xu X, et al. Exosome-derived micrornas contribute to prostate cancer chemoresistance. Int J Oncol. 2016;49(2):838–46.CrossRef
16.
go back to reference Majid S, Dar AA, Saini S, Yamamura S, Hirata H, Tanaka Y, et al. Microrna-205-directed transcriptional activation of tumor suppressor genes in prostate cancer. Cancer. 2010;116(24):5637–49.CrossRef Majid S, Dar AA, Saini S, Yamamura S, Hirata H, Tanaka Y, et al. Microrna-205-directed transcriptional activation of tumor suppressor genes in prostate cancer. Cancer. 2010;116(24):5637–49.CrossRef
17.
go back to reference He D, Ma L, Feng R, Zhang L, Jiang Y, Zhang Y, et al. Analyzing large-scale samples highlights significant association between rs10411210 polymorphism and colorectal cancer. Biomed Pharmacother. 2015;74:164–8.CrossRef He D, Ma L, Feng R, Zhang L, Jiang Y, Zhang Y, et al. Analyzing large-scale samples highlights significant association between rs10411210 polymorphism and colorectal cancer. Biomed Pharmacother. 2015;74:164–8.CrossRef
18.
go back to reference Danussi C, Akavia UD, Niola F, Jovic A, Lasorella A, Pe'er D, et al. Rhpn2 drives mesenchymal transformation in malignant glioma by triggering rhoa activation. Cancer Res. 2013;73(16):5140–50.CrossRef Danussi C, Akavia UD, Niola F, Jovic A, Lasorella A, Pe'er D, et al. Rhpn2 drives mesenchymal transformation in malignant glioma by triggering rhoa activation. Cancer Res. 2013;73(16):5140–50.CrossRef
19.
go back to reference Kang BW, Jeon HS, Chae YS, Lee SJ, Park JY, Choi JE, et al. Association between gwas-identified genetic variations and disease prognosis for patients with colorectal cancer. PLoS One. 2015;10(3):e0119649.CrossRef Kang BW, Jeon HS, Chae YS, Lee SJ, Park JY, Choi JE, et al. Association between gwas-identified genetic variations and disease prognosis for patients with colorectal cancer. PLoS One. 2015;10(3):e0119649.CrossRef
20.
go back to reference Nayak RR, Bernal WE, Lee JW, Kearns MJ, Cheung VG. Stress-induced changes in gene interactions in human cells. Nucleic Acids Res. 2014;42(3):1757–71.CrossRef Nayak RR, Bernal WE, Lee JW, Kearns MJ, Cheung VG. Stress-induced changes in gene interactions in human cells. Nucleic Acids Res. 2014;42(3):1757–71.CrossRef
21.
go back to reference Kim J, Mizokami A, Shin M, Izumi K, Konaka H, Kadono Y, et al. Sod3 acts as a tumor suppressor in pc-3 prostate cancer cells via hydrogen peroxide accumulation. Anticancer Res. 2014;34(6):2821–31.PubMed Kim J, Mizokami A, Shin M, Izumi K, Konaka H, Kadono Y, et al. Sod3 acts as a tumor suppressor in pc-3 prostate cancer cells via hydrogen peroxide accumulation. Anticancer Res. 2014;34(6):2821–31.PubMed
22.
go back to reference Li R, Yan G, Li Q, Sun H, Hu Y, Sun J, et al. Microrna-145 protects cardiomyocytes against hydrogen peroxide (h (2) o (2))-induced apoptosis through targeting the mitochondria apoptotic pathway. PLoS One. 2012;7(9):e44907.CrossRef Li R, Yan G, Li Q, Sun H, Hu Y, Sun J, et al. Microrna-145 protects cardiomyocytes against hydrogen peroxide (h (2) o (2))-induced apoptosis through targeting the mitochondria apoptotic pathway. PLoS One. 2012;7(9):e44907.CrossRef
23.
go back to reference Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319(5867):1244–7.CrossRef Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319(5867):1244–7.CrossRef
24.
go back to reference Yan W, Wu X, Zhou W, Fong MY, Cao M, Liu J, et al. Cancer-cell-secreted exosomal mir-105 promotes tumour growth through the myc-dependent metabolic reprogramming of stromal cells. Nat Cell Biol. 2018;20(5):597–609.CrossRef Yan W, Wu X, Zhou W, Fong MY, Cao M, Liu J, et al. Cancer-cell-secreted exosomal mir-105 promotes tumour growth through the myc-dependent metabolic reprogramming of stromal cells. Nat Cell Biol. 2018;20(5):597–609.CrossRef
25.
go back to reference Ferreira ADF, Cunha PDS, Carregal VM, da Silva PC, de Miranda MC, Kunrath-Lima M, et al. Extracellular vesicles from adipose-derived mesenchymal stem/stromal cells accelerate migration and activate akt pathway in human keratinocytes and fibroblasts independently of mir-205 activity. Stem Cells Int. 2017;2017:9841035.CrossRef Ferreira ADF, Cunha PDS, Carregal VM, da Silva PC, de Miranda MC, Kunrath-Lima M, et al. Extracellular vesicles from adipose-derived mesenchymal stem/stromal cells accelerate migration and activate akt pathway in human keratinocytes and fibroblasts independently of mir-205 activity. Stem Cells Int. 2017;2017:9841035.CrossRef
26.
go back to reference Mekhail SM, Yousef PG, Jackinsky SW, Pasic M, Yousef GM. Mirna in prostate cancer: new prospects for old challenges. EJIFCC. 2014;25(1):79–98.PubMedPubMedCentral Mekhail SM, Yousef PG, Jackinsky SW, Pasic M, Yousef GM. Mirna in prostate cancer: new prospects for old challenges. EJIFCC. 2014;25(1):79–98.PubMedPubMedCentral
27.
go back to reference Ono M, Kosaka N, Tominaga N, Yoshioka Y, Takeshita F, Takahashi RU, et al. Exosomes from bone marrow mesenchymal stem cells contain a microrna that promotes dormancy in metastatic breast cancer cells. Sci Signal. 2014;7(332):ra63.CrossRef Ono M, Kosaka N, Tominaga N, Yoshioka Y, Takeshita F, Takahashi RU, et al. Exosomes from bone marrow mesenchymal stem cells contain a microrna that promotes dormancy in metastatic breast cancer cells. Sci Signal. 2014;7(332):ra63.CrossRef
28.
go back to reference Ru P, Steele R, Newhall P, Phillips NJ, Toth K, Ray RB. Mirna-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling. Mol Cancer Ther. 2012;11(5):1166–73.CrossRef Ru P, Steele R, Newhall P, Phillips NJ, Toth K, Ray RB. Mirna-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling. Mol Cancer Ther. 2012;11(5):1166–73.CrossRef
29.
go back to reference Majid S, Dar AA, Saini S, Shahryari V, Arora S, Zaman MS, et al. Mirna-34b inhibits prostate cancer through demethylation, active chromatin modifications, and akt pathways. Clin Cancer Res. 2013;19(1):73–84.CrossRef Majid S, Dar AA, Saini S, Shahryari V, Arora S, Zaman MS, et al. Mirna-34b inhibits prostate cancer through demethylation, active chromatin modifications, and akt pathways. Clin Cancer Res. 2013;19(1):73–84.CrossRef
30.
go back to reference Wang W, Liu J, Wu Q. Mir-205 suppresses autophagy and enhances radiosensitivity of prostate cancer cells by targeting tp53inp1. Eur Rev Med Pharmacol Sci. 2016;20(1):92–100.PubMed Wang W, Liu J, Wu Q. Mir-205 suppresses autophagy and enhances radiosensitivity of prostate cancer cells by targeting tp53inp1. Eur Rev Med Pharmacol Sci. 2016;20(1):92–100.PubMed
31.
go back to reference Zhao L, Gu C, Ye M, Zhang Z, Li L, Fan W, et al. Integration analysis of microrna and mrna paired expression profiling identifies deregulated microrna-transcription factor-gene regulatory networks in ovarian endometriosis. Reprod Biol Endocrinol. 2018;16(1):4.CrossRef Zhao L, Gu C, Ye M, Zhang Z, Li L, Fan W, et al. Integration analysis of microrna and mrna paired expression profiling identifies deregulated microrna-transcription factor-gene regulatory networks in ovarian endometriosis. Reprod Biol Endocrinol. 2018;16(1):4.CrossRef
32.
go back to reference Hannafon BN, Ding WQ. Intercellular communication by exosome-derived micrornas in cancer. Int J Mol Sci. 2013;14(7):14240–69.CrossRef Hannafon BN, Ding WQ. Intercellular communication by exosome-derived micrornas in cancer. Int J Mol Sci. 2013;14(7):14240–69.CrossRef
33.
go back to reference Wang N, Li Q, Feng NH, Cheng G, Guan ZL, Wang Y, et al. Mir-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth. Asian J Androl. 2013;15(6):735–41.CrossRef Wang N, Li Q, Feng NH, Cheng G, Guan ZL, Wang Y, et al. Mir-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth. Asian J Androl. 2013;15(6):735–41.CrossRef
34.
go back to reference Bhagirath D, Yang TL, Bucay N, Sekhon K, Majid S, Shahryari V, et al. Microrna-1246 is an exosomal biomarker for aggressive prostate cancer. Cancer Res. 2018;78(7):1833–44.CrossRef Bhagirath D, Yang TL, Bucay N, Sekhon K, Majid S, Shahryari V, et al. Microrna-1246 is an exosomal biomarker for aggressive prostate cancer. Cancer Res. 2018;78(7):1833–44.CrossRef
35.
go back to reference Liang X, Zhang L, Wang S, Han Q, Zhao RC. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring mir-125a. J Cell Sci. 2016;129(11):2182–9.CrossRef Liang X, Zhang L, Wang S, Han Q, Zhao RC. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring mir-125a. J Cell Sci. 2016;129(11):2182–9.CrossRef
Metadata
Title
Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2
Authors
Shuangjian Jiang
Chengqiang Mo
Shengjie Guo
Jintao Zhuang
Bin Huang
Xiaopeng Mao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1488-1

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