Cited by 53Extracellular vesicles in diseaseMicroRNA in disease regulationCancer-related molecular mechanisms research

Presence of Circulating miR-145, miR-155, and miR-382 in Exosomes Isolated from Serum of Breast Cancer Patients and Healthy Donors

Open access
Gonzalez-Villasana, Vianey, Rashed, Mohammed H., Gonzalez-Cantú, Yessica, Bayraktar, Recep, Menchaca-Arredondo, Jorge Luis, Vazquez-Guillen, Jose Manuel, Rodriguez-Padilla, Cristina, Lopez-Berestein, Gabriel +1 more·2019·Disease Markers

Abstract

miR-145, miR-155, and miR-382 have been proposed as noninvasive biomarkers to distinguish breast cancer patients from healthy individuals. However, it is unknown if these three miRNAs are secreted by exosomes. Thus, we hypothesized that miR-145, miR-155, and miR-382 in breast cancer patients are present in exosomes. We isolated exosomes from serum of breast cancer patients and healthy donors, then we characterized them according to their shape, size, and exosome markers by scanning electron microscopy, atomic force microscopy, nanoparticle tracking analysis (NTA), and Western blot and determined the exosome concentration in all samples by NTA. Later, exosomal small RNA extraction was done to determine the expression levels of miR-145, miR-155, and miR-382 by qRT-PCR. We observed a round shape of exosomes with a mean size of 119.84 nm in breast cancer patients and 115.4 nm in healthy donors. All exosomes present the proteins CD63, Alix, Tsg, CD9, and CD81 commonly used as markers. Moreover, we found a significantly high concentration of exosomes in breast cancer patients with stages I, III, and IV compared to healthy donors. We detected miR-145, miR-155, and miR-382 in the exosomes isolated from serum of breast cancer patients and healthy donors. Our results show that the exosomes isolated from the serum of breast cancer patients and healthy donors contains miR-145, miR-155, and miR-382 but not in a selective manner in breast cancer patients. Moreover, our data support the association between exosome concentration and the presence of breast cancer, opening the possibility to study how miRNAs packaged into exosomes play a role in BC progression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2019/6852917

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 43

  1. [1]Siegel R. L. Miller K. D. Jemal A. Cancer statistics, 2018 CA: a Cancer Journal for Clinicians 2018 68 1 7 30 10.3322/caac.21442 2-s2.0-85040049759 29313949 · DOI
  2. [3]Ambros V. The functions of animal microRNAs Nature 2004 431 7006 350 355 10.1038/nature02871 2-s2.0-4644309196 15372042 · DOI · Paper page
  3. [4]Bayraktar R. Van Roosbroeck K. Calin G. A. Cell-to-cell communication: microRNAs as hormones Molecular Oncology 2017 11 12 1673 1686 10.1002/1878-0261.12144 2-s2.0-85032967117 29024380 PMC5709614 · DOI · Paper page
  4. [5]Calin G. A. Ferracin M. Cimmino A. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia New England Journal of Medicine 2005 353 17 1793 1801 10.1056/NEJMoa050995 2-s2.0-27244434788 16251535 · DOI
  5. [6]Mandujano-Tinoco E. A. García-Venzor A. Melendez-Zajgla J. Maldonado V. New emerging roles of microRNAs in breast cancer Breast Cancer Research and Treatment 2018 171 2 247 259 10.1007/s10549-018-4850-7 2-s2.0-85048257055 29948402 · DOI
  6. [7]Mitchell P. S. Parkin R. K. Kroh E. M. Circulating microRNAs as stable blood-based markers for cancer detection Proceedings of the National Academy of Sciences of the United States of America 2008 105 30 10513 10518 10.1073/pnas.0804549105 2-s2.0-48749122914 18663219 PMC2492472 · DOI · Paper page
  7. [8]Turchinovich A. Samatov T. R. Tonevitsky A. G. Burwinkel B. Circulating miRNAs: cell-cell communication function? Frontiers in Genetics 2013 4 p. 119 10.3389/fgene.2013.00119 2-s2.0-84883496908 PMC3695387 23825476 · DOI
  8. [9]Liu X. Liu X. Wu Y. MicroRNAs in biofluids are novel tools for bladder cancer screening Oncotarget 2017 8 19 32370 32379 10.18632/oncotarget.16026 2-s2.0-85019061321 28423688 PMC5458291 · DOI
  9. [10]Lan H. Lu H. Wang X. Jin H. MicroRNAs as potential biomarkers in cancer: opportunities and challenges BioMed Research International 2015 2015 17 125094 10.1155/2015/125094 2-s2.0-84926675821 25874201 PMC4385606 · DOI
  10. [11]Bahrami A. Aledavood A. Anvari K. The prognostic and therapeutic application of microRNAs in breast cancer: tissue and circulating microRNAs Journal of Cellular Physiology 2018 233 2 774 786 10.1002/jcp.25813 2-s2.0-85017136677 28109133 · DOI
  11. [12]Sato-Kuwabara Y. Melo S. A. Soares F. A. Calin G. A. The fusion of two worlds: non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications (review) International Journal of Oncology 2015 46 1 17 27 10.3892/ijo.2014.2712 2-s2.0-84917711130 25338714 PMC4238728 · DOI
  12. [13]Rajagopal C. Harikumar K. B. The origin and functions of exosomes in cancer Frontiers in Oncology 2018 8 66 10.3389/fonc.2018.00066 2-s2.0-85044364477 PMC5869252 29616188 · DOI
  13. [14]Hesari A. Golrokh Moghadam S. A. Siasi A. Tumor-derived exosomes: potential biomarker or therapeutic target in breast cancer? Journal of Cellular Biochemistry 2018 119 6 4236 4240 10.1002/jcb.26364 2-s2.0-85043330548 28833502 · DOI
  14. [15]Kalluri R. The biology and function of exosomes in cancer The Journal of Clinical Investigation 2016 126 4 1208 1215 10.1172/JCI81135 2-s2.0-84964597652 27035812 PMC4811149 · DOI
  15. [16]He Y. Deng F. Yang S. Exosomal microRNA: a novel biomarker for breast cancer Biomarkers in Medicine 2018 12 2 177 188 10.2217/bmm-2017-0305 2-s2.0-85041387418 29151358 · DOI
  16. [17]Yoshikawa M. Iinuma H. Umemoto Y. Yanagisawa T. Matsumoto A. Jinno H. Exosome‑encapsulated microRNA‑223‑3p as a minimally invasive biomarker for the early detection of invasive breast cancer Oncology Letters 2018 15 6 9584 9592 10.3892/ol.2018.8457 2-s2.0-85046414394 29805680 PMC5958689 · DOI
  17. [18]Wang M. Ji S. Shao G. Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients Clinical & Translational Oncology 2018 20 7 906 911 10.1007/s12094-017-1805-0 2-s2.0-85034059238 29143228 · DOI
  18. [19]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 2017 8 41 69934 69944 10.18632/oncotarget.19482 2-s2.0-85030213045 29050253 PMC5642528 · DOI
  19. [20]Mar-Aguilar F. Mendoza-Ramírez J. A. Malagón-Santiago I. Serum circulating microRNA profiling for identification of potential breast cancer biomarkers Disease Markers 2013 34 3 169 10.1155/2013/259454 PMC3810231 23334650 · DOI
  20. [21]Zheng M. Sun X. Li Y. Zuo W. MicroRNA-145 inhibits growth and migration of breast cancer cells through targeting oncoprotein ROCK1 Tumour Biology 2016 37 6 8189 8196 10.1007/s13277-015-4722-2 2-s2.0-84951989529 26715279 · DOI
  21. [22]Zhao H. Kang X. Xia X. miR-145 suppresses breast cancer cell migration by targeting FSCN-1 and inhibiting epithelial-mesenchymal transition American Journal of Translational Research 2016 8 7 3106 3114 27508031 PMC4969447
  22. [23]Tang L. Wei D. Yan F. MicroRNA-145 functions as a tumor suppressor by targeting matrix metalloproteinase 11 and Rab GTPase family 27a in triple-negative breast cancer Cancer Gene Therapy 2016 23 8 258 265 10.1038/cgt.2016.27 2-s2.0-84976530571 27364572 · DOI
  23. [24]Hemmatzadeh M. Mohammadi H. Jadidi-Niaragh F. Asghari F. Yousefi M. The role of oncomirs in the pathogenesis and treatment of breast cancer Biomedicine & Pharmacotherapy 2016 78 129 139 10.1016/j.biopha.2016.01.026 2-s2.0-84958640151 26898434 · DOI
  24. [25]Kim S. Song J. H. Kim S. Loss of oncogenic miR-155 in tumor cells promotes tumor growth by enhancing C/EBP-β-mediated MDSC infiltration Oncotarget 2016 7 10 11094 11112 10.18632/oncotarget.7150 2-s2.0-84962026496 26848978 PMC4905460 · DOI
  25. [26]Ho J. Y. Hsu R. J. Liu J. M. MicroRNA-382-5p aggravates breast cancer progression by regulating the RERG/Ras/ERK signaling axis Oncotarget 2017 8 14 22443 22459 10.18632/oncotarget.12338 2-s2.0-85016959297 27705918 PMC5410235 · DOI
  26. [27]Horcas I. Fernández R. Gómez-Rodríguez J. M. Colchero J. Gómez-Herrero J. Baro A. M. WSXM: A software for scanning probe microscopy and a tool for nanotechnology The Review of Scientific Instruments 2007 78 1, article 013705 10.1063/1.2432410 2-s2.0-34047109564 17503926 · DOI
  27. [28]Livak K. J. Schmittgen T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔC T method Methods 2001 25 4 402 408 10.1006/meth.2001.1262 2-s2.0-0035710746 11846609 · DOI · Paper page
  28. [29]Jeyaram A. Jay S. M. Preservation and Storage stability of extracellular vesicles for therapeutic applications The AAPS Journal 2018 20 1 10.1208/s12248-017-0160-y 2-s2.0-85037032817 PMC6582961 29181730 · DOI
  29. [30]Kalra H. Adda C. G. Liem M. Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma Proteomics 2013 13 22 3354 3364 10.1002/pmic.201300282 2-s2.0-84888042782 24115447 · DOI
  30. [31]Zhao L. Yu J. Wang J. Li H. Che J. Cao B. Isolation and identification of miRNAs in exosomes derived from serum of colon cancer patients Journal of Cancer 2017 8 7 1145 1152 10.7150/jca.18026 2-s2.0-85017663525 28607588 PMC5463428 · DOI
  31. [32]Jenjaroenpun P. Kremenska Y. Nair V. M. Kremenskoy M. Joseph B. Kurochkin I. V. Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing PeerJ 2013 1 p. e201 10.7717/peerj.201 2-s2.0-84888329506 24255815 PMC3828613 · DOI
  32. [33]Melo S. A. Sugimoto H. O’Connell J. T. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis Cancer Cell 2014 26 5 707 721 10.1016/j.ccell.2014.09.005 2-s2.0-84911966357 25446899 PMC4254633 · DOI
  33. [34]Rashed M. H. Bayraktar E. Helal G. K. Exosomes: from garbage bins to promising therapeutic targets International Journal of Molecular Sciences 2017 18 3 10.3390/ijms18030538 2-s2.0-85014551872 28257101 PMC5372554 · DOI
  34. [35]Eldh M. Lötvall J. Malmhäll C. Ekström K. Importance of RNA isolation methods for analysis of exosomal RNA: evaluation of different methods Molecular Immunology 2012 50 4 278 286 10.1016/j.molimm.2012.02.001 2-s2.0-84858330248 22424315 · DOI
  35. [36]Schwarzenbach H. da Silva A. M. Calin G. Pantel K. Data normalization strategies for microRNA quantification Clinical Chemistry 2015 61 11 1333 1342 10.1373/clinchem.2015.239459 2-s2.0-84946576277 26408530 PMC4890630 · DOI · Paper page
  36. [37]Lange T. Stracke S. Rettig R. Identification of miR-16 as an endogenous reference gene for the normalization of urinary exosomal miRNA expression data from CKD patients PLoS One 2017 12 8, article e0183435 10.1371/journal.pone.0183435 2-s2.0-85029170567 PMC5578666 28859135 · DOI
  37. [38]Wang J. Chen J. Chang P. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease Cancer Prevention Research (Philadelphia, Pa.) 2009 2 9 807 813 10.1158/1940-6207.CAPR-09-0094 2-s2.0-70449700281 PMC5859193 19723895 · DOI
  38. [39]Gallo A. Tandon M. Alevizos I. Illei G. G. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes PLoS One 2012 7 3, article e30679 10.1371/journal.pone.0030679 2-s2.0-84857968441 PMC3302865 22427800 · DOI · Paper page
  39. [40]Turchinovich A. Weiz L. Langheinz A. Burwinkel B. Characterization of extracellular circulating microRNA Nucleic Acids Research 2011 39 16 7223 7233 10.1093/nar/gkr254 2-s2.0-80052381608 21609964 PMC3167594 · DOI · Paper page
  40. [41]Arroyo J. D. Chevillet J. R. Kroh E. M. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma Proceedings of the National Academy of Sciences of the United States of America 2011 108 12 5003 5008 10.1073/pnas.1019055108 2-s2.0-79953202200 21383194 PMC3064324 · DOI · Paper page
  41. [42]Hamam R. Hamam D. Alsaleh K. A. Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers Cell Death & Disease 2017 8 9, article e3045 10.1038/cddis.2017.440 2-s2.0-85042726147 PMC5636984 28880270 · DOI
  42. [43]Mihelich B. L. Dambal S. Lin S. Nonn L. miR-182, of the miR-183 cluster family, is packaged in exosomes and is detected in human exosomes from serum, breast cells and prostate cells Oncology Letters 2016 12 2 1197 1203 10.3892/ol.2016.4710 2-s2.0-84977136920 27446418 PMC4950593 · DOI
  43. [44]Eichelser C. Stückrath I. Müller V. Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients Oncotarget 2014 5 20 9650 9663 10.18632/oncotarget.2520 2-s2.0-84923699297 25333260 PMC4259427 · DOI

Cited by

Sorted by citations

Authors
Gonzalez-Villasana, V., Rashed, M. H., Gonzalez-Cantú, Y., Bayraktar, R., Menchaca-Arredondo, J. L., Vazquez-Guillen, J. M., Rodriguez-Padilla, C., Lopez-Berestein, G., & Resendez-Perez, D.
Affiliations
  • Universidad Autónoma de Nuevo León, College of Biological Sciences, Department of Cellular Biology and Genetics, San Nicolás de los Garza, Nuevo León, Mexico
  • The University of Texas MD Anderson Cancer Center (US)
  • Universidad Autónoma de Nuevo León, College of Biological Sciences, Laboratory of Immunology and Virology, San Nicolás de los Garza, Nuevo León, Mexico
  • Universidad Autónoma de Nuevo León, College of Physics and Mathematics, Research Center in Physics and Mathematic Sciences, San Nicolás de los Garza, Nuevo León, Mexico
  • Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Venue
Disease Markers
Publisher
Wiley
Published
2019-02-12
Volume
2019
Pages
1-9
ISSN
  • 0278-0240 (ISSN-L)
  • 1875-8630
OpenAlex
W2914867806
Cited by
53
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 14 · 2019: 3
FWCI
2.81
Type
journal article
Language
en
Open access
Locations
  • Disease Markers (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Universidad Autónoma de Nuevo León
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
breast cancer, exosomes, circulating microRNAs, miR-145, miR-155, miR-382, serum exosomes, exosomal biomarkers, non-invasive biomarkers, exosome size, tumor stage
MeSH terms
Cell-Free Nucleic Acids, Adult, Aged, Breast Neoplasms, Female, Humans, Middle Aged, Biomarkers, Tumor, MicroRNAs, Exosomes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review