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 1/2015

Open Access 01-12-2015 | Research article

MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid

Authors: Sonja Khan, Deirdre Wall, Catherine Curran, John Newell, Michael J Kerin, Roisin M Dwyer

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a.

Methods

Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3.

Results

The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log10 RQ, p < 0.05). The levels of both RARβ and THRα gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RARβ (r = 0.31, p < 0.001) and also with THRα (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T4 alone did not stimulate miR-10a expression, the combination of T4 and ATRA was found to have a positive synergistic effect.

Conclusion

The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the microRNA.
Appendix
Available only for authorised users
Literature
1.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97. doi:S0092867404000455.CrossRefPubMed
2.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66. doi:10.1038/nrc1997.CrossRefPubMed
3.
Bieche I, Vacher S, Lallemand F, Tozlu-Kara S, Bennani H, Beuzelin M, et al. Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidy. Mol Cancer. 2011;10:23. doi:10.1186/1476-4598-10-23.CrossRefPubMedPubMedCentral
4.
Sassen S, Miska EA, Caldas C. MicroRNA: implications for cancer. Virchows Arch. 2008;452(1):1–10. doi:10.1007/s00428-007-0532-2.CrossRefPubMed
5.
Kuhling H, Alm P, Olsson H, Ferno M, Baldetorp B, Parwaresch R, et al. Expression of cyclins E, A, and B, and prognosis in lymph node-negative breast cancer. J Pathol. 2003;199(4):424–31. doi:10.1002/path.1322.CrossRefPubMed
6.
Rudolph P, Kuhling H, Alm P, Ferno M, Baldetorp B, Olsson H, et al. Differential prognostic impact of the cyclins E and B in premenopausal and postmenopausal women with lymph node-negative breast cancer. Int J Cancer. 2003;105(5):674–80. doi:10.1002/ijc.11132.CrossRefPubMed
7.
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(7):673–82. doi:10.1634/theoncologist.2010-0103.CrossRefPubMedPubMedCentral
8.
Tan Y, Zhang B, Wu T, Skogerbo G, Zhu X, Guo X, et al. Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells. BMC Mol Biol. 2009;10:12. doi:10.1186/1471-2199-10-12.CrossRefPubMedPubMedCentral
9.
Lund AH. miR-10 in development and cancer. Cell Death Differ. 2010;17(2):209–14. doi:10.1038/cdd.2009.58.CrossRefPubMed
10.
Jia HY, Zhang ZY, Zou DL, Wang B, Yan YM, Luo M, et al. MicroRNA-10a is down-regulated by DNA methylation and functions as a tumor suppressor in gastric cancer cells. PloS One. 2014;9(1). doi:ARTN e88057 doi:10.1371/journal.pone.0088057.
11.
Zeng TH, Li GL. MicroRNA-10a enhances the metastatic potential of cervical cancer cells by targeting phosphatase and tensin homologue. Mol Med Rep. 2014;10(3):1377–82. doi:10.3892/mmr.2014.2370.PubMed
12.
Hudson J, Duncavage E, Tamburrino A, Salerno P, Xi L, Raffeld M, et al. Overexpression of miR-10a and miR-375 and downregulation of YAP1 in medullary thyroid carcinoma. Exp Mol Pathol. 2013;95(1):62–7. doi:10.1016/j.yexmp.2013.05.001.CrossRefPubMedPubMedCentral
13.
Meseguer S, Mudduluru G, Escamilla JM, Allgayer H, Barettino D. MicroRNAs-10a and -10b contribute to retinoic acid-induced differentiation of neuroblastoma cells and target the alternative splicing regulatory factor SFRS1 (SF2/ASF). J Biol Chem. 2011;286(6):4150–64. doi:10.1074/jbc.M110.167817.CrossRefPubMed
14.
Foley NH, Bray I, Watters KM, Das S, Bryan K, Bernas T, et al. MicroRNAs 10a and 10b are potent inducers of neuroblastoma cell differentiation through targeting of nuclear receptor corepressor 2. Cell Death Differ. 2011;18(7):1089–98. doi:10.1038/cdd.2010.172.CrossRefPubMedPubMedCentral
15.
16.
Chang CH, Fan TC, Yu JC, Liao GS, Lin YC, Shih A, et al. The prognostic significance of RUNX2 and miR-10a/10b and their inter-relationship in breast cancer. J Transl Med. 2014;12(1):257. doi:10.1186/s12967-014-0257-3.CrossRefPubMedPubMedCentral
17.
Perez-Rivas LG, Jerez JM, Carmona R, de Luque V, Vicioso L, Claros MG, et al. A microRNA signature associated with early recurrence in breast cancer. PloS One. 2014;9(3). doi:ARTN e91884. doi:10.1371/journal.pone.0091884.
18.
Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer. 2010;127(8):1785–94. doi:10.1002/ijc.25191.CrossRefPubMed
19.
Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM, et al. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med. 1990;323(12):795–801. doi:10.1056/NEJM199009203231205.CrossRefPubMed
20.
Kakizuka A, Miller WH, Umesono K, Warrell RP, Frankel SR, Murty VVVS, et al. Chromosomal translocation T(15–17) in human acute promyelocytic leukemia fuses Rar-Alpha with a novel putative transcription factor, Pml. Cell. 1991;66(4):663–74. doi:10.1016/0092-8674(91)90112-C.CrossRefPubMed
21.
Lippman SM, Benner SE, Hong WK. Retinoid chemoprevention studies in upper aerodigestive tract and lung carcinogenesis. Cancer Res. 1994;54(7):S2025–8.
22.
Alizadeh F, Bolhassani A, Khavari A, Bathaie SZ, Naji T, Bidgoli SA. Retinoids and their biological effects against cancer. Int Immunopharmacol. 2014;18(1):43–9. doi:10.1016/j.intimp.2013.10.027.CrossRefPubMed
23.
Theodosiou M, Laudet V, Schubert M. From carrot to clinic: an overview of the retinoic acid signaling pathway. Cell Mol Life Sci. 2010;67(9):1423–45. doi:10.1007/s00018-010-0268-z.CrossRefPubMed
24.
Prakash P, Russell RM, Krinsky NI. In vitro inhibition of proliferation of estrogen-dependent and estrogen-independent human breast cancer cells treated with carotenoids or retinoids. J Nutr. 2001;131(5):1574–80.PubMed
25.
Rubin M, Fenig E, Rosenauer A, Menendez-Botet C, Achkar C, Bentel JM, et al. 9-Cis retinoic acid inhibits growth of breast cancer cells and down-regulates estrogen receptor RNA and protein. Cancer Res. 1994;54(24):6549–56.PubMed
26.
Toma S, Isnardi L, Raffo P, Riccardi L, Dastoli G, Apfel C, et al. RARalpha antagonist Ro 41–5253 inhibits proliferation and induces apoptosis in breast-cancer cell lines. Int J Cancer. 1998;78(1):86–94.CrossRefPubMed
27.
Ryan J, Curran CE, Hennessy E, Newell J, Morris JC, Kerin MJ, et al. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. PLoS One. 2011;6(1):e16023. doi:10.1371/journal.pone.0016023.CrossRefPubMedPubMedCentral
28.
Widschwendter M, Berger J, Daxenbichler G, Muller-Holzner E, Widschwendter A, Mayr A, et al. Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer. Cancer Res. 1997;57(19):4158–61.PubMed
29.
Wu Q, Dawson MI, Zheng Y, Hobbs PD, Agadir A, Jong L, et al. Inhibition of trans-retinoic acid-resistant human breast cancer cell growth by retinoid X receptor-selective retinoids. Mol Cell Biol. 1997;17(11):6598–608.CrossRefPubMedPubMedCentral
30.
Yang QF, Sakurai T, Kakudo K. Retinoid, retinoic acid receptor beta and breast cancer. Breast Cancer Res Treat. 2002;76(2):167–73. doi:10.1023/A:1020576606004.CrossRefPubMed
31.
Silva J, Domínguez G, González-Sancho J, García J, Silva J, García-Andrade C, et al. Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer. Oncogene. 2002;21(27):4307–16.CrossRefPubMed
32.
Lee S, Privalsky ML. Heterodimers of retinoic acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties. Mol Endocrinol. 2005;19(4):863–78. doi:10.1210/me.2004-0210.CrossRefPubMedPubMedCentral
33.
Barton KN, Stricker H, Brown SL, Elshaikh M, Aref I, Lu M, et al. Phase I study of noninvasive imaging of adenovirus-mediated gene expression in the human prostate. Mol Ther. 2008;16(10):1761–9. doi:10.1038/mt.2008.172.CrossRefPubMedPubMedCentral
34.
Takahashi H, Kanno T, Nakayamada S, Hirahara K, Sciume G, Muljo SA, et al. TGF-beta and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat Immunol. 2012;13(6):587–95. doi:10.1038/ni.2286.CrossRefPubMedPubMedCentral
35.
Weiss FU, Marques IJ, Woltering JM, Vlecken DH, Aghdassi A, Partecke LI, et al. Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer. Gastroenterology. 2009;137(6):2136–45. e1-7. doi:10.1053/j.gastro.2009.08.065.CrossRefPubMed
36.
Huang H, Xie C, Sun X, Ritchie RP, Zhang J, Chen YE. miR-10a contributes to retinoid acid-induced smooth muscle cell differentiation. J Biol Chem. 2010;285(13):9383–9. doi:10.1074/jbc.M109.095612.CrossRefPubMedPubMedCentral
37.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25(4):402–8. doi:10.1006/meth.2001.1262 S1046-2023(01)91262-9.CrossRefPubMed
38.
McNeill RE, Miller N, Kerin MJ. Evaluation and validation of candidate endogenous control genes for real-time quantitative PCR studies of breast cancer. BMC Mol Biol. 2007;8:107. doi:10.1186/1471-2199-8-107.CrossRefPubMedPubMedCentral
39.
Davoren PA, McNeill RE, Lowery AJ, Kerin MJ, Miller N. Identification of suitable endogenous control genes for microRNA gene expression analysis in human breast cancer. BMC Mol Biol. 2008;9:76. doi:10.1186/1471-2199-9-76.CrossRefPubMedPubMedCentral
40.
Stadthagen G, Tehler D, Hoyland-Kroghsbo NM, Wen J, Krogh A, Jensen KT, et al. Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice. PLoS Genet. 2013;9(10):e1003913. doi:10.1371/journal.pgen.1003913.CrossRefPubMedPubMedCentral
Metadata
Title
MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid
Authors
Sonja Khan
Deirdre Wall
Catherine Curran
John Newell
Michael J Kerin
Roisin M Dwyer
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1374-y

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma

Research article

The effect of pre-diagnostic vitamin D supplementation on cancer survival in women: a cohort study within the UK Clinical Practice Research Datalink

Research article

Texture analysis on MR images helps predicting non-response to NAC in breast cancer

Research article

Fractal analysis of nuclear histology integrates tumor and stromal features into a single prognostic factor of the oral cancer microenvironment

Research article

Conventional transarterial chemoembolization versus drug-eluting bead transarterial chemoembolization for the treatment of hepatocellular carcinoma

Research article

Negative effect of cyclin D1 overexpression on recurrence-free survival in stage II-IIIA lung adenocarcinoma and its expression modulation by vorinostat in vitro
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