We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Short Communication

Expression profiles of exosomal miRNAs isolated from plasma of patients with desmoplastic small round cell tumor

    Marta Colletti

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    Authors contributed equally

    Search for more papers by this author

    ,
    Alessandro Paolini

    Research Laboratories, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy

    Authors contributed equally

    Search for more papers by this author

    ,
    Angela Galardi

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    ,
    Virginia Di Paolo

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    ,
    Luisa Pascucci

    Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy

    ,
    Ida Russo

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    ,
    Biagio De Angelis

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    ,
    Hector Peinado

    Microenvironment & Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029 Madrid, Spain

    ,
    Rita De Vito

    Department of Pathology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio 4, 00165 Rome, Italy

    ,
    Giuseppe M Milano

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    ,
    Franco Locatelli

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    Department of Ginecology/Obstetrics & Pediatrics, Sapienza University of Rome, Italy

    ,
    Andrea Masotti

    **Author for correspondence: Tel.: +39 06 6859 2650; Fax: +39 06 23323 4321;

    E-mail Address: andrea.masotti@opbg.net

    Research Laboratories, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy

    &
    Angela Di Giannatale

    *Author for correspondence: Tel.: +39 06 6859 3707; Fax: +39 06 6859 2904;

    E-mail Address: angela.digiannatale@opbg.net

    Department of Pediatric Hematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant’ Onofrio, 4, 00165 Rome, Italy

    Published Online:https://doi.org/10.2217/epi-2018-0179

    Aim: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal tumor, lacking biomarkers for diagnosis, treatment stratification and prognosis. We investigated the exosomal miRNA profile in plasma samples collected from DSRCT patients, evaluating their potential as circulating biomarkers for this tumor. Patients & methods: We isolated exosomes from plasma of three DSRCT adolescents and four age-matched healthy controls; expression of circulating miRNAs was quantified by qPCR. Results: We identified 55 miRNAs significantly modulated compared with healthy controls. Among these miRNAs, 14 were highly dysregulated in at least one patient and 5 were expressed in all patients. Conclusion: To our knowledge, this is the first report describing exosomal miRNAs as promising biomarkers to characterize disease status in DSRCT patients.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Gerald WL, Rosai J. Desmoplastic small cell tumor with divergent differentiation. Pediatr. Pathol. 9(2), 177–183 (1989).
    • 2 Umeda K, Saida S, Yamaguchi H et al. Central nervous system recurrence of desmoplastic small round cell tumor following aggressive multimodal therapy: a case report. Oncol. Lett. 11(1), 856–860 (2016).
    • 3 Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP. Results of multimodal treatment for desmoplastic small round cell tumors. J. Pediatr. Surg. 40(1), 251–255 (2005).
    • 4 Ladanyi M, Gerald WL. Specificity of the EWS/WT1 gene fusion for desmoplastic small round cell tumour. J. Pathol. 180(4), 462 (1996). • Emphasizes the importance and specificity of the EWS/WT1 fusion gene for diagnosis of desmoplastic small round cell tumors.
    • 5 Lee SB, Kolquist KA, Nichols K et al. The EWS-WT1 translocation product induces PDGFA in desmoplastic small round-cell tumour. Nat. Genet. 17(3), 309–313 (1997).
    • 6 Karnieli E, Werner H, Rauscher FJ 3rd, Benjamin LE, LeRoith D. The IGF-receptor gene promoter is a molecular target for the Ewing's sarcoma-Wilms’ tumor 1 fusion protein. J. Biol. Chem. 271(32), 19304–19309 (1996).
    • 7 Saito T, Yokotsuka M, Motoi T et al. EWS-WT1 chimeric protein in desmoplastic small round cell tumor is a potent transactivator of FGFR4. Cancer Sci. Ther. 4, 335–340 (2012).
    • 8 Bandopadhayay P, Jabbour AM, Riffkin C et al. The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts. BMC Cancer 13, 585 (2013).
    • 9 Wang H, Peng R, Wang J, Qin Z, Xue L. Circulating microRNAs as potential cancer biomarkers: the advantage and disadvantage. Clin. Epigenetics 10, 59 (2018).
    • 10 Bracken CP, Scott HS, Goodall GJ. A network-biology perspective of microRNA function and dysfunction in cancer. Nat. Rev. Genet. 17(12), 719–732 (2016).
    • 11 Salehi M, Sharifi M. Exosomal miRNAs as novel cancer biomarkers: challenges and opportunities. J. Cell Physiol. 233(9), 6370–6380 (2018).
    • 12 Hoshino A, Costa-Silva B, Shen TL et al. Tumour exosome integrins determine organotropic metastasis. Nature 527(7578), 329–335 (2015). • Describing the specific targeting for certain sites of exosomes.
    • 13 Guduric-Fuchs J, O'Connor A, Camp B, O'Neill CL, Medina RJ, Simpson DA. Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genomics 13, 357 (2012).
    • 14 Kim KY, Hwang YJ, Jung MK et al. A multifunctional protein EWS regulates the expression of drosha and microRNAs. Cell Death Differ. 21(1), 136–145 (2014).
    • 15 Masotti A, Alisi A. Integrated bioinformatics analysis of microRNA expression profiles for an in-depth understanding of pathogenic mechanisms in non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 27(2), 187–188 (2012).
    • 16 Fan Y, Siklenka K, Arora SK, Ribeiro P, Kimmins S, Xia J. miRNet – dissecting miRNA-target interactions and functional associations through network-based visual analysis. Nucleic Acids Res. 44(W1), W135–W141 (2016).
    • 17 Huang da W, Sherman BT, Zheng X et al. Extracting biological meaning from large gene lists with DAVID. Curr. Protoc. Bioinformatics Chapter 13: Unit 13.11 (2009).
    • 18 Peng Y, Croce CM. The role of microRNAs in human cancer. Signal Transduct. Target Ther. 1, 15004 (2016).
    • 19 Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–659 (2007). •• The first evidence of the ability of exosomes to deliver nucleic acids to cells at a distance.
    • 20 Tang S, Chen Y, Feng S et al. MiR-483-5p promotes IGF-II transcription and is associated with poor prognosis of hepatocellular carcinoma. Oncotarget 8(59), 99871–99888 (2017).
    • 21 Sueta A, Yamamoto Y, Tomiguchi M, Takeshita T, Yamamoto-Ibusuki M, Iwase H. Differential expression of exosomal miRNAs between breast cancer patients with and without recurrence. Oncotarget 8(41), 69934–69944 (2017).
    • 22 Zhang Y, Li T, Guo P et al. MiR-424-5p reversed epithelial–mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression. Sci. Rep. 4, 6248 (2014).
    • 23 Thor T, Künkele A, Pajtler KW et al. MiR-34a deficiency accelerates medulloblastoma formation in vivo. Int. J. Cancer 136(10), 2293–2303 (2015).
    • 24 Guessous F, Zhang Y, Kofman A et al. microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle 9(6), 1031–1036 (2010).
    • 25 Galardi A, Colletti M, Businaro P, Quintarelli C, Locatelli F, Di Giannatale A. MicroRNAs in neuroblastoma: biomarkers with therapeutic potential. Curr. Med. Chem. 25(5), 584–600 (2018). •• Very interesting review describing the role and the importance of several dysregulated miRNAs in a pediatric cancer such as neuroblastoma.
    • 26 Nan D, Haiying Wu, Tao T, Erxuan P. NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2. Onco Targets Ther. 10, 4905–4915 (2017).
    • 27 Youguang P, Fangfang Z, Haiyan W, Shanbao C. MiR-34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene. Sci. Rep. 7, 44218 (2017).
    • 28 Youguang P, Fangfang Z, Yinpeng L et al. The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene. BMC Cancer 17(1), 45 (2017).
    • 29 Chen J, Wu FX, Luo HL et al. Berberine upregulates miR-22-3p to suppress hepatocellular carcinoma cell proliferation by targeting Sp1. Am. J. Transl. Res. 8(11), 4932–4941 (2016).
    • 30 Lv KT, Liu Z, Feng J et al. MiR-22-3p Regulates cell proliferation and inhibits cell apoptosis through targeting the eIF4EBP3 gene in human cervical squamous carcinoma cells. Int. J. Med. Sci. 15(2), 142–152 (2018).
    • 31 Kuo WT, Yu SY, Li SC et al. MicroRNA-324 in human cancer: miR-324-5p and miR-324-3p have distinct biological functions in human cancer. Anticancer Res. 36(10), 5189–5196 (2016).
    • 32 Cao L, Xie B, Yang X et al. MiR-324-5p Suppresses hepatocellular carcinoma cell invasion by counteracting ECM degradation through post-transcriptionally downregulating ETS1 and SP1. PLoS ONE 10(7), e0133074 (2015).
    • 33 Li XR, Chu HJ, Lv T, Wang L, Kong SF, Dai SZ. miR-342-3p suppresses proliferation, migration and invasion by targeting FOXM1 in human cervical cancer. FEBS Lett. 588, 3298–3307 (2014).
    • 34 Xue X, Fei X, Hou W, Zhang Y, Liu L, Hu R. miR-342-3p suppresses cell proliferation and migration by targeting AGR2 in non-small cell lung cancer. Cancer Lett. 412, 170–178 (2018).
    • 35 Liu W, Kang L, Han J et al. miR-342-3p suppresses hepatocellular carcinoma proliferation through inhibition of IGF-1R-mediated Warburg effect. Onco. Targets Ther. 11, 1643–1653 (2018).
    • 36 Leoncini PP, Bertaina A, Papaioannou D et al. MicroRNA fingerprints in juvenile myelomonocytic leukemia (JMML) identified miR-150-5p as a tumor suppressor and potential target for treatment. Oncotarget 7(34), 55395–55408 (2016).
    • 37 Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 4, 2980 (2013).
    • 38 Bullock MD, Silva AM, Kanlikilicer-Unaldi P et al. Exosomal non-coding RNAs: ciagnostic, prognostic and therapeutic applications in cancer. Non-coding RNA 1(1), 53–68 (2015). •• Very intriguing review exploring the therapeutic and biomarker potential of exosomes with particular focus on the noncoding RNA, microRNA and long-noncoding RNA.
    • 39 Yi-Lei Z, Ruo-Chen W, Ken C, Brian ZR, Li S. Roles of Rap1 signaling in tumor cell migration and invasion. Cancer Biol. Med. 14(1), 90–99 (2017).