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
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
Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 3/2014

01-03-2014 | Educational Series - Blue Series

MicroRNA-21 in breast cancer: diagnostic and prognostic potential

Authors: J. Chen, X. Wang

Published in: Clinical and Translational Oncology | Issue 3/2014

Login to get access

Abstract

Breast cancer is the most common malignancy in women and is considered as a complex and heterogeneous disease. The identification of novel biomarkers for early detection of breast cancer and prediction of disease outcome is urgently required. MicroRNAs (miRNAs) are small non-coding endogenous RNA molecules that act to regulate gene expression and play vital roles in many crucial processes. Recent evidence demonstrates that miRNAs could emerge as revolutionary sources of biomarkers for cancer diagnosis and prognosis. miR-21 is one of the most commonly observed aberrant miRNAs in a variety of cancers including breast cancer. Emerging studies show that miR-21 could be measured stably and easily in tumor tissues, formalin-fixed paraffin-embedded tissues and blood circulation. In this review, we will summarize the current evidence of miR-21 as a promising biomarker for diagnosis and prognosis in breast cancer. We will also discuss the issues and challenges of miR-21 as a potential biomarker in future clinical applications.
Literature
1.
2.
Murphy IG, Dillon MF, Doherty AO, McDermott EW, Kelly G, O’Higgins N, et al. Analysis of patients with false negative mammography and symptomatic breast carcinoma. J Surg Oncol. 2007;96:457–63.PubMedCrossRef
3.
Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.PubMedCrossRef
4.
Uehara M, Kinoshita T, Hojo T, Akashi-Tanaka S, Iwamoto E, Fukutomi T. Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in breast cancer. Int J Clin Oncol. 2008;13:447–51.PubMedCrossRef
5.
Opstal-van Winden AW, Rodenburg W, Pennings JL, van Oostrom CT, Beijnen JH, Peeters PH, et al. A bead-based multiplexed immunoassay to evaluate breast cancer biomarkers for early detection in pre-diagnostic serum. Int J Mol Sci. 2012;13:13587–604.PubMedCentralPubMedCrossRef
6.
Ng EK, Wong CL, Ma ES, Kwong A. MicroRNAs as new players for diagnosis, prognosis, and therapeutic targets in breast cancer. J Oncol. 2009;2009:305420.PubMedCentralPubMedCrossRef
7.
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.PubMedCrossRef
8.
9.
Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769–73.PubMedCrossRef
10.
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 USA. 2004;101:2999–3004.PubMedCrossRef
11.
Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene. 2006;25:6188–96.PubMedCrossRef
12.
Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.PubMedCrossRef
13.
Wu CW, Ng SS, Dong YJ, Ng SC, Leung WW, Lee CW, et al. Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut. 2012;61:739–45.PubMedCrossRef
14.
Jamieson NB, Morran DC, Morton JP, Ali A, Dickson EJ, Carter CR, et al. MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. Clin Cancer Res. 2012;18:534–45.PubMedCrossRef
15.
Wang S, Li Q, Wang K, Dai Y, Yang J, Xue S, et al. Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer. Clin Transl Oncol. 2013. doi:10.​1007/​s12094-013-1014-4.PubMedCentral
16.
Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S. A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS ONE. 2010;5:e13735.PubMedCentralPubMedCrossRef
17.
Madhavan D, Zucknick M, Wallwiener M, Cuk K, Modugno C, Scharpff M, et al. Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer. Clin Cancer Res. 2012;18:5972–82.PubMedCrossRef
18.
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.PubMedCrossRef
19.
Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006;103:2257–61.PubMedCrossRef
20.
Wang B, Zhang Q. The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors. J Cancer Res Clin Oncol. 2012;138:1659–66.PubMedCrossRef
21.
Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120:1046–54.PubMedCentralPubMedCrossRef
22.
Nam EJ, Yoon H, Kim SW, Kim H, Kim YT, Kim JH, et al. MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 2008;14:2690–5.PubMedCrossRef
23.
Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91.PubMedCrossRef
24.
Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008;14:2348–60.PubMedCrossRef
25.
Heneghan HM, Miller N, Kelly R, Newell J, Kerin MJ. Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. Oncologist. 2010;15:673–82.PubMedCrossRef
26.
Qian B, Katsaros D, Lu L, Preti M, Durando A, Arisio R, et al. High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1. Breast Cancer Res Treat. 2009;117:131–40.PubMedCrossRef
27.
Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65:6029–33.PubMedCrossRef
28.
29.
Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, et al. Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res. 2007;67:11612–20.PubMedCrossRef
30.
Chen L, Li Y, Fu Y, Peng J, Mo MH, Stamatakos M, et al. Role of deregulated microRNAs in breast cancer progression using FFPE tissue. PLoS ONE. 2013;8:e54213.PubMedCentralPubMedCrossRef
31.
Huang GL, Zhang XH, Guo GL, Huang KT, Yang KY, Shen X, et al. Clinical significance of miR-21 expression in breast cancer: SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma. Oncol Rep. 2009;21:673–9.PubMed
32.
Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119:586–5893.PubMedCrossRef
33.
Song B, Wang C, Liu J, Wang X, Lv L, Wei L, et al. MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. J Exp Clin Cancer Res. 2010;29:29.PubMedCrossRef
34.
Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 2013;139:223–9.PubMedCentralPubMedCrossRef
35.
Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS ONE. 2013;8:e53141.PubMedCentralPubMedCrossRef
36.
Savad S, Mehdipour P, Miryounesi M, Shirkoohi R, Fereidooni F, Mansouri F, et al. Expression analysis of MiR-21, MiR-205, and MiR-342 in breast cancer in Iran. Asian Pac J Cancer Prev. 2012;13:873–7.PubMedCrossRef
37.
Mar-Aguilar F, Luna-Aguirre CM, Moreno-Rocha JC, Araiza-Chavez J, Trevino V, Rodriguez-Padilla C, et al. Differential expression of miR-21, miR-125b and miR-191 in breast cancer tissue. Asia Pac J Clin Oncol. 2013;9:53–9.PubMedCrossRef
38.
Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.PubMedCrossRef
39.
40.
Lee JA, Lee HY, Lee ES, Kim I, Bae JW. Prognostic implications of microRNA-21 overexpression in invasive ductal carcinomas of the breast. J Breast Cancer. 2011;14:269–75.PubMedCentralPubMedCrossRef
41.
Lehmann U, Streichert T, Otto B, Albat C, Hasemeier B, Christgen H, et al. Identification of differentially expressed microRNAs in human male breast cancer. BMC Cancer. 2010;10:109.PubMedCentralPubMedCrossRef
42.
Ozgun A, Karagoz B, Bilgi O, Tuncel T, Baloglu H, Kandemir EG. MicroRNA-21 as an indicator of aggressive phenotype in breast cancer. Onkologie. 2013;36:115–8.PubMedCrossRef
43.
Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141:672–5.PubMedCrossRef
44.
Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, et al. hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res. 2008;14:1340–8.PubMedCrossRef
45.
Ota D, Mimori K, Yokobori T, Iwatsuki M, Kataoka A, Masuda N, et al. Identification of recurrence-related microRNAs in the bone marrow of breast cancer patients. Int J Oncol. 2011;38:955–62.PubMed
46.
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.PubMedCrossRef
47.
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–8.PubMedCrossRef
48.
Lima LG, Chammas R, Monteiro RQ, Moreira ME, Barcinski MA. Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner. Cancer Lett. 2009;283:168–75.PubMedCrossRef
49.
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. 2007;9:654–9.PubMedCrossRef
50.
Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101:2087–92.PubMedCrossRef
51.
Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2:ra81.PubMed
52.
Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA. 2011;108:5003–8.PubMedCrossRef
53.
Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH, et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene. 2008;27:4373–9.PubMedCrossRef
54.
Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 2008;283:1026–33.PubMedCrossRef
55.
Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 2007;282:14328–36.PubMedCrossRef
56.
Wickramasinghe NS, Manavalan TT, Dougherty SM, Riggs KA, Li Y, Klinge CM. Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids Res. 2009;37:2584–95.PubMedCentralPubMedCrossRef
57.
Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 2008;18:350–9.PubMedCrossRef
58.
Yang Y, Chaerkady R, Beer MA, Mendell JT, Pandey A. Identification of miR-21 targets in breast cancer cells using a quantitative proteomic approach. Proteomics. 2009;9:1374–84.PubMedCentralPubMedCrossRef
59.
Cheng HH, Yi HS, Kim Y, Kroh EM, Chien JW, Eaton KD, et al. Plasma processing conditions substantially influence circulating microRNA biomarker levels. PLoS ONE. 2013;8:e64795.PubMedCentralPubMedCrossRef
60.
Metadata
Title
MicroRNA-21 in breast cancer: diagnostic and prognostic potential
Authors
J. Chen
X. Wang
Publication date
01-03-2014
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 3/2014
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1132-z

Other articles of this Issue 3/2014

Clinical and Translational Oncology 3/2014 Go to the issue

Research Article

The clinical significance of memory T cells and its subsets in gastric cancer

Research Article

Overexpressed transcription factor FOXM1 is a potential diagnostic and adverse prognostic factor in postoperational gastric cancer patients

Research Article

Oropharyngeal cancer related to Human Papilloma Virus: incidence and prognosis in Madrid, Spain

Research Article

PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer

Research Article

Combined preoperative CEA and CD44v6 improves prognostic value in patients with stage I and stage II colorectal cancer

Research Article

Microvesicle microRNA profiles and functional roles between chronic hepatitis B and hepatocellular carcinoma
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