Identification of six key miRNAs associated with breast cancer through screening large‑scale microarray data

Liang,Faqing; Yang,Meng; Tong,Ning; Fang,Jinju; Pan,Yanbin; Li,Jianmin; Zhang,Xiao

doi:10.3892/ol.2018.9175

October-2018 Volume 16 Issue 4

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

October-2018 Volume 16 Issue 4

Full Size Image

Article Open Access

Identification of six key miRNAs associated with breast cancer through screening large‑scale microarray data

Authors:
- Faqing Liang
- Meng Yang
- Ning Tong
- Jinju Fang
- Yanbin Pan
- Jianmin Li
- Xiao Zhang
View Affiliations / Copyright

Affiliations: Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Dermatology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530031, P.R. China, Department of Neurology, Heze Minicipal Hospital, Heze, Shandong 274000, P.R. China, Department of Breast Surgery, Hospital of The University of Electronic Science and Technology of China and The Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China

Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 4159-4168
|
Published online on: July 19, 2018

https://doi.org/10.3892/ol.2018.9175
Expand metrics +

Abstract

Breast Cancer (BC) is one of the most common primary malignant tumors, which is life threatening. Previous studies have demonstrated that microRNAs (miRNA) may regulate or affect the incidence of BC. However, results of these studies are inconsistent, due to factors including the different sequencing platforms and sample selection methods used. To explore the key miRNAs involved in the pathogenesis of BC, and to use these miRNAs to monitor the tumor progression of BC, a systematic review was performed on the previous studies examining BC miRNA; the function of the target genes that were modulated by these key miRNAs were also analyzed. A total of 8 representative miRNA datasets examining the pathogenesis of BC were selected. Key miRNAs were identified by comparing the overlap between these datasets. Then, the target genes of these key miRNAs were predicted through TargetScan. Furthermore, functional enrichment analysis of target genes and transcription factor (TF) binding analysis was also performed using the Database for Annotation, Visualization and Integrated Discovery and Tfacts database, respectively. A total of 6 key miRNAs were identified by comparing the differentially expressed miRNAs datasets in the pathogenesis of BC. Compared with normal tissues, 3 miRNAs were upregulated: Hsa‑miR‑21b; hsa‑miR‑29b; and hsa‑miR‑155; and 3 miRNAs were downregulated: Hsa‑miR‑10b; hsa‑miR‑125; and hsa‑miR‑145. The target genes regulated by the up‑ and downregulated miRNAs were significantly enriched in the biological processes of ‘transcriptional regulation’, and these target genes depended on RNA polymerase II promoter and DNA template, respective to the up‑ and downregulated genes. The downregulated key miRNAs were specifically enriched in the biological processes of ‘ephrin receptor signaling pathway’ (GO: 0048013) and ‘axon guidance’ (GO: 0007411). TF analysis of the key miRNA target genes revealed that 104 TFs interacted with the 319 target genes of the upregulated miRNAs, while the 92 TFs interacted with the 254 target genes of the downregulated miRNAs. In total, there were 133 TFs and 63 (47.3%) TFs shared by the 2 types (up‑ and downregulated) of target genes. In summary, 6 key miRNAs in BC were identified by systematic review; the corresponding target genes and TFs that bind to these target genes were also identified, and the potential functions of target genes were revealed. These data may be beneficial to increasing the accuracy of BC treatment through monitoring miRNA.

View Figures

View References

1	DeSantis CE, Ma J, Goding Sauer A, Newman LA and Jemal A: Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 67:439–448. 2017. View Article : Google Scholar : PubMed/NCBI
2	Nowbar AN, Howard JP, Finegold JA, Asaria P and Francis DP: 2014 global geographic analysis of mortality from ischaemic heart disease by country, age and income: Statistics from world health organisation and united nations. Int J Cardiol. 174:293–298. 2014. View Article : Google Scholar : PubMed/NCBI
3	Stewart BW and Wild CP: The global and regional burden of cancerWorld Cancer Report 2014. World Health Organization; Geneva: pp. 162014
4	Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: GLOBOCAN 2012 Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. v1.0. International Agency for Research on Cancer; Lyon, France: 2013 Decembet 12–2016
5	Kosir MA: Breast Cancer. MSD manual consumer version. https://www.msdmanuals.com/home/women-s-health-issues/breast-disorders/breast-cancer%C2%A0Decembet 12–2016
6	Reeder JG and Vogel VG: Breast cancer prevention. Cancer Treatment and Res. 141:149–164. 2008. View Article : Google Scholar
7	Gage M, Wattendorf D and Henry LR: Translational advances regarding hereditary breast cancer syndromes. J Surg Oncol. 105:444–451. 2012. View Article : Google Scholar : PubMed/NCBI
8	Colditz GA, Kaphingst KA, Hankinson SE and Rosner B: Family history and risk of breast cancer: Nurses' health study. Breast Cancer Res Treat. 133:1097–1104. 2012. View Article : Google Scholar : PubMed/NCBI
9	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
10	Dalmay T: Mechanism of miRNA-mediated repression of mRNA translation. Essays Biochem. 54:29–38. 2013. View Article : Google Scholar : PubMed/NCBI
11	Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
12	Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI
13	Zhang C, Xie SH, Xu B, Lu S and Liu P: Digitalis use and the risk of breast cancer: A systematic review and meta-analysis. Drug Saf. 40:285–292. 2017. View Article : Google Scholar : PubMed/NCBI
14	Griffiths-Jones S, Saini HK, van Dongen S and Enright AJ: miRBase: Tools for microRNA genomics. Nucleic Acids Res. 36:D154–D158. 2008. View Article : Google Scholar : PubMed/NCBI
15	Kozomara A and Griffiths-Jones S: miRBase: Integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39:152–157. 2011. View Article : Google Scholar
16	Lewis BP, Shih Ih, Jones-Rhoades MW, Bartel DP and Burge CB: Prediction of mammalian microRNA targets. Cell. 115:787–798. 2003. View Article : Google Scholar : PubMed/NCBI
17	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
18	Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC and Lempicki RA: DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 4:P32003. View Article : Google Scholar : PubMed/NCBI
19	Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: Tool for the unification of biology. Nat Genet. 25:25–29. 2000. View Article : Google Scholar : PubMed/NCBI
20	Kanehisa M, Goto S, Kawashima S, Okuno Y and Hattori M: The KEGG resource for deciphering the genome. Nucleic Acids Res. 32:D277–D280. 2004. View Article : Google Scholar : PubMed/NCBI
21	Essaghir A, Toffalini F, Knoops L, Kallin A, van Helden J and Demoulin JB: Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data. Nucleic Acids Res. 38:e1202010. View Article : Google Scholar : PubMed/NCBI
22	Essaghir A and Demoulin JB: A minimal connected network of transcription factors regulated in human tumors and its application to the quest for universal cancer biomarkers. PLoS One. 7:e396662012. View Article : Google Scholar : PubMed/NCBI
23	Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, et al: Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 138:592–603. 2009. View Article : Google Scholar : PubMed/NCBI
24	Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:pp. 2257–2261. 2006; View Article : Google Scholar : PubMed/NCBI
25	Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J and Kerin MJ: Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 251:499–505. 2010. View Article : Google Scholar : PubMed/NCBI
26	Lowery AJ, Miller N, McNeill RE and Kerin MJ: MicroRNAs as prognostic indicators and therapeutic targets: Potential effect on breast cancer management. Clin Cancer Res. 14:360–365. 2008. View Article : Google Scholar : PubMed/NCBI
27	Kastl L, Brown I and Schofield AC: miRNA-34a is associated with docetaxel resistance in human breast cancer cells. Breast Cancer Res Treat. 131:445–454. 2012. View Article : Google Scholar : PubMed/NCBI
28	Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX and Shao JY: MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 14:2348–2360. 2008. View Article : Google Scholar : PubMed/NCBI
29	Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H and Hu C: Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 139:223–229. 2013. View Article : Google Scholar : PubMed/NCBI
30	Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9:189–198. 2006. View Article : Google Scholar : PubMed/NCBI
31	Selcuklu SD, Donoghue MT and Spillane C: miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 37:918–925. 2009. View Article : Google Scholar : PubMed/NCBI
32	Kong W, He L, Richards EJ, Challa S, Xu CX, Permuth-Wey J, Lancaster JM, Coppola D, Sellers TA, Djeu JY and Cheng JQ: Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer. Oncogene. 33:679–689. 2014. View Article : Google Scholar : PubMed/NCBI
33	Jiang H, Zhang G, Wu JH and Jiang CP: Diverse roles of miR-29 in cancer (review). Oncol Rep. 31:1509–1516. 2014. View Article : Google Scholar : PubMed/NCBI
34	Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP and James RJ: Reduced accumulation of specific MicroRNAs in colorectal neoplasia. Mol Cancer Res. 1:882–891. 2003.PubMed/NCBI
35	Sun YM, Lin KY and Chen YQ: Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol. 6:62013. View Article : Google Scholar : PubMed/NCBI
36	Huang L, Luo J, Cai Q, Pan Q, Zeng H, Guo Z, Dong W, Huang J and Lin T: MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3. Int J Cancer. 128:1758–1769. 2011. View Article : Google Scholar : PubMed/NCBI
37	Cowden Dahl KD, Dahl R, Kruichak JN and Hudson LG: The epidermal growth factor receptor responsive miR-125a represses mesenchymal morphology in ovarian cancer cells. Neoplasia. 11:1208–1215. 2009. View Article : Google Scholar : PubMed/NCBI
38	Rajabi H, Jin C, Ahmad R, McClary AC, Joshi MD and Kufe D: Mucin 1 oncoprotein expression is suppressed by the miR-125b oncomir. Genes Cancer. 1:62–68. 2010. View Article : Google Scholar : PubMed/NCBI
39	Kaenel P, Mosimann M and Andres AC: The multifaceted roles of Eph/ephrin signaling in breast cancer. Cell Adh Migr. 6:138–147. 2012. View Article : Google Scholar : PubMed/NCBI
40	Harburg GC and Hinck L: Navigating breast cancer: Axon guidance molecules as breast cancer tumor suppressors and oncogenes. J Mammary Gland Biol Neoplasia. 16:257–270. 2011. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Identification of six key miRNAs associated with breast cancer through screening large‑scale microarray data

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles