Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours

Authors: Malgorzata Bulkowska, Agata Rybicka, Kerem Mert Senses, Katarzyna Ulewicz, Katarzyna Witt, Joanna Szymanska, Bartlomiej Taciak, Robert Klopfleisch, Eva Hellmén, Izabella Dolka, Ali O. Gure, Joanna Mucha, Mariusz Mikow, Slawomir Gizinski, Magdalena Krol

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans.

Methods

Expression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases) and in 25 control samples were evaluated. The profiling was performed using microarrays. Significance Analysis of Microarrays test was applied in the analysis of microarray data (both unsupervised and supervised data analyses were performed). Validation of the obtained results was performed using real-time qPCR. Subsequently, predicted targets for the microRNAs were searched for in miRBase.

Results

Results of the unsupervised analysis indicate that the primary factor separating the samples is the metastasis status. Predicted targets for microRNAs differentially expressed in the metastatic vs. non-metastatic group are mostly engaged in cell cycle regulation, cell differentiation and DNA-damage repair. On the other hand, the supervised analysis reveals clusters of differentially expressed microRNAs unique for the tumour type, malignancy grade and metastasis factor.

Conclusions

The most significant difference in microRNA expression was observed between the metastatic and non-metastatic group, which suggests a more important role of microRNAs in the metastasis process than in the malignant transformation. Moreover, the differentially expressed microRNAs constitute potential metastasis markers. However, validation of cfa-miR-144, cfa-miR-32 and cfa-miR-374a levels in blood samples did not follow changes observed in the non-metastatic and metastatic tumours.
Appendix
Available only for authorised users
Literature
1.
Egenvall A, Bonnett BN, Ohagen P, Olson P, Hedhammar A, von Euler H. Incidence of and survival after mammary tumors in a population of over 80,000 insured female dogs in Sweden from 1995 to 2002. Prev Vet Med. 2005;69:109–27.CrossRefPubMed
2.
Misdorp W. In: Meuten DJ, editor. Tumors of the mammary gland. 4th ed. Ames: Iowa State Press; 2002. p. 575–606.
3.
Shafiee R, Javanbakht J, Atyabi N, Kheradmand P, Kheradmand D, Bahrami A, et al. Diagnosis, classification and grading of canine mammary tumours as a model to study human breast cancer: an Clinico-Cytohistopathological study with environmental factors influencing public health and medicine. Cancer Cell Int. 2013;13:79.CrossRefPubMedPubMedCentral
4.
Weigelt B, Horlings HM, Kreike B, Hayes MM, Hauptmann M, Wessels LF, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216:141–50.CrossRefPubMed
5.
Gilbertson SR, Kurzman ID, Zachrau RE, Hurvitz AI, Black MM. Canine mammary epithelial neoplasms: biologic implications of morphologic characteristics assessed in 232 dogs. Vet Pathol. 1983;20:127–42.CrossRefPubMed
6.
Hellmen E, Svensson S. Progression of canine mammary tumours as reflected by DNA ploidy in primary tumours and their metastases. J Comp Pathol. 1995;113:327–42.CrossRefPubMed
7.
Rosol TJ, Tannehill-Gregg SH, LeRoy BE, Mandl S, Contag CH. Animal models of bone metastasis. Cancer. 2003;97(Suppl 3):748–57.CrossRefPubMed
8.
Al-Kahiry W, Omer HH, Saeed NM, Hamid GA. Late presentation of breast cancer in Aden, Yemen. Gulf J Oncolog. 2011;9:7–11.
9.
Boggs RM, Wright ZM, Stickney MJ, Porter WW, Murphy KE. MicroRNA expression in canine mammary cancer. Mamm Genome. 2008;19:561–9.CrossRefPubMed
10.
Uva P, Aurisicchio L, Watters J, Loboda A, Kulkarni A, Castle J, et al. Comparative expression pathway analysis of human and canine mammary tumors. BMC Genomics. 2009;10:135.CrossRefPubMedPubMedCentral
11.
12.
Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.CrossRefPubMed
13.
Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMedPubMedCentral
14.
Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26:745–52.CrossRefPubMedPubMedCentral
15.
Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC. Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res. 2006;66:1277–81.CrossRefPubMed
16.
Mertens-Talcott SU, Chintharlapalli S, Li X, Safe S. The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res. 2007;67:11001–11.CrossRefPubMed
17.
Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.CrossRefPubMed
18.
19.
Hellmen E, Bergstrom R, Holmberg L, Spangberg IB, Hansson K, Lindgren A. Prognostic factors in canine mammary tumors: a multivariate study of 202 consecutive cases. Vet Pathol. 1993;30:20–7.CrossRefPubMed
20.
Misdorp W, Else RW, Hellmen E, Lipscomb TP. Histologic classification of mammary tumor of the dog and the cat in: WHO international histological classification tumor of domestic animals. Washington, DC. 1999;7:3–29.
21.
Elston CW, Ellis IO. Assessment of histological grade. In: Elston CW, Ellis IO, editors. Systemic pathology: the breast, vol. 13. 3rd ed. Edinburgh: Churchill-Livingstone; 1998. p. 365–84.
22.
Rossum Gv. Python tutorial. Technical Report CS-R9526. Centrum voor Wiskunde en Informatica (CWI), Amsterdam. 1995.
23.
Hunter JD. Matplotlib: a 2D graphics environment. Comput Sci Eng. 2007;9:90–5.CrossRef
24.
Blondal T, Jensby Nielsen S, Baker A, Andreasen D, Mouritzen P, Wrang Teilum M, et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods. 2013;59:S1–6.CrossRefPubMed
25.
Kirschner MB, Edelman JJ, Kao SC, Vallely MP, van Zandwijk N, Reid G. The impact of Hemolysis on cell-free microRNA biomarkers. Front Genet. 2013;4:94.PubMedPubMedCentral
26.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3:1101–8.CrossRefPubMed
27.
Klopfleisch R, Lenze D, Hummel M, Gruber AD. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles. BMC Cancer. 2010;10:618.CrossRefPubMedPubMedCentral
28.
Fu L, Li Z, Zhu J, Wang P, Fan G, Dai Y, et al. Serum expression levels of microRNA-382-3p, −598-3p, −1246 and −184 in breast cancer patients. Oncol Lett. 2016;12:269–74.PubMedPubMedCentral
29.
Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39:D152–7.CrossRefPubMed
30.
Biagioni F, Bossel Ben-Moshe N, Fontemaggi G, Canu V, Mori F, Antoniani B, et al. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours. EMBO Mol Med. 2012;4:1214–29.CrossRefPubMedPubMedCentral
31.
Luo Q, Li X, Li J, Kong X, Zhang J, Chen L, et al. MiR-15a is underexpressed and inhibits the cell cycle by targeting CCNE1 in breast cancer. Int J Oncol. 2013;43:1212–8.CrossRefPubMed
32.
Yang J, Zhang Z, Chen C, Liu Y, Si Q, Chuang TH, et al. MicroRNA-19a-3p inhibits breast cancer progression and metastasis by inducing macrophage polarization through downregulated expression of Fra-1 proto-oncogene. Oncogene. 2014;33:3014–23.CrossRefPubMed
33.
Liu XX, Li XJ, Zhang B, Liang YJ, Zhou CX, Cao DX, et al. MicroRNA-26b is underexpressed in human breast cancer and induces cell apoptosis by targeting SLC7A11. FEBS Lett. 2011;585:1363–7.CrossRefPubMed
34.
Mathsyaraja H, Thies K, Taffany DA, Deighan C, Liu T, Yu L, et al. CSF1-ETS2-induced microRNA in myeloid cells promote metastatic tumor growth. Oncogene. 2015;34:3651–61.CrossRefPubMed
35.
Zhang N, Wang X, Huo Q, Sun M, Cai C, Liu Z, et al. MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin. Oncogene. 2014;33:3119–28.CrossRefPubMed
36.
Tanic M, Yanowsky K, Rodriguez-Antona C, Andres R, Marquez-Rodas I, Osorio A, et al. Deregulated miRNAs in hereditary breast cancer revealed a role for miR-30c in regulating KRAS oncogene. PLoS One. 2012;7:e38847.CrossRefPubMedPubMedCentral
37.
38.
39.
Cimino D, De Pitta C, Orso F, Zampini M, Casara S, Penna E, et al. miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J. 2013;27:1223–35.CrossRefPubMed
40.
Bisso A, Faleschini M, Zampa F, Capaci V, De Santa J, Santarpia L, et al. Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle. 2013;12:1679–87.CrossRefPubMedPubMedCentral
41.
Luo Q, Wei C, Li X, Li J, Chen L, Huang Y, et al. MicroRNA-195-5p is a potential diagnostic and therapeutic target for breast cancer. Oncol Rep. 2014;31:1096–102.CrossRefPubMedPubMedCentral
42.
Luthra R, Singh RR, Luthra MG, Li YX, Hannah C, Romans AM, et al. MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene. 2008;27(52):6667–78.CrossRefPubMed
43.
He DX, XT G, Jiang L, Jin J, Ma XA. Methylation-based regulatory network for microRNA 320a in chemoresistant breast cancer. Mol Pharmacol. 2014;86:536–47.CrossRefPubMed
44.
Cai J, Guan H, Fang L, Yang Y, Zhu X, Yuan J, et al. MicroRNA-374a activates Wnt/beta-catenin signaling to promote breast cancer metastasis. J Clin Invest. 2013;123:566–79.CrossRefPubMedPubMedCentral
45.
Liu Y, Lai L, Chen Q, Song Y, Xu S, Ma F, et al. MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J Immunol. 2012;188:5500–10.CrossRefPubMed
46.
47.
Yoshimura H, Michishita M, Ohkusu-Tsukada K, Takahashi K. Increased presence of stromal myofibroblasts and tenascin-C with malignant progression in canine mammary tumors. Vet Pathol. 2011;48:313–21.CrossRefPubMed
48.
Lancon A, Michaille JJ, Latruffe N. Effects of dietary phytophenols on the expression of microRNAs involved in mammalian cell homeostasis. J Sci Food Agric. 2013;93:3155–64.CrossRefPubMed
49.
Dong N, Tang X, Xu B. miRNA-181a inhibits the proliferation, migration, and epithelial-mesenchymal transition of lens epithelial cells. Invest Ophthalmol Vis Sci. 2015;56:993–1001.CrossRefPubMed
50.
Wang L, Zhou L, Jiang P, Lu L, Chen X, Lan H, et al. Loss of miR-29 in myoblasts contributes to dystrophic muscle pathogenesis. Mol Ther. 2012;20:1222–33.CrossRefPubMedPubMedCentral
51.
52.
Chen J, Yao D, Li Y, Chen H, He C, Ding N, et al. Serum microRNA expression levels can predict lymph node metastasis in patients with early-stage cervical squamous cell carcinoma. Int J Mol Med. 2013;32:557–67.CrossRefPubMedPubMedCentral
53.
Steudemann C, Bauersachs S, Weber K, Wess G. Detection and comparison of microRNA expression in the serum of Doberman pinschers with dilated cardiomyopathy and healthy controls. BMC Vet Res. 2013;9:12.CrossRefPubMedPubMedCentral
54.
Kirschner MB, Kao SC, Edelman JJ, Armstrong NJ, Vallely MP, van Zandwijk N, et al. Haemolysis during sample preparation alters microRNA content of plasma. PLoS One. 2011;6:e24145.CrossRefPubMedPubMedCentral
55.
Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 2010;251:499–505.CrossRefPubMed
56.
Huang Z, Huang D, Ni S, Peng Z, Sheng W, Plasma DX. microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 2010;127:118–26.CrossRefPubMed
Metadata
Title
MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours
Authors
Malgorzata Bulkowska
Agata Rybicka
Kerem Mert Senses
Katarzyna Ulewicz
Katarzyna Witt
Joanna Szymanska
Bartlomiej Taciak
Robert Klopfleisch
Eva Hellmén
Izabella Dolka
Ali O. Gure
Joanna Mucha
Mariusz Mikow
Slawomir Gizinski
Magdalena Krol
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3751-1

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue

Database

King’s Health Partners’ Prostate Cancer Biobank (KHP PCaBB)

Research article

Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA

Research article

Ageing, exposure to pollution, and interactions between climate change and local seasons as oxidant conditions predicting incident hematologic malignancy at KINSHASA University clinics, Democratic Republic of CONGO (DRC)

Case report

Gastric hepatoid adenocarcinoma resulting in a spontaneous gastric perforation: a case report and review of the literature

Research article

The prognosis of invasive micropapillary carcinoma compared with invasive ductal carcinoma in the breast: a meta-analysis

Research article

Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits