Interrelation of the Circulating and Tissue MicroRNA-21 with Tissue PDCD4 Expression and the Invasiveness of Iraqi Female Breast Tumors
- 20 Downloads
The changes in the translational repression and variation in mRNA degradation induced by micro RNA are important aspects of tumorigenesis. The association of microRNA-21 with clinicopathologic features and expression of programed cell death 4 (PDCD4) in Iraqi female’s with breast tumors has not been studied. MicroRNAs were extracted from a set of 60 breast tumor tissues and blood samples of females with breast cancer and benign breast lesions obtained after breast-reductive surgery, and only blood samples from 30 normal volunteers. These extracts were evaluated for miR-21 expression by quantitative RT-PCR. Analysis of PDCD4 protein expression was carried out as miR-21 target gene by immunohistochemical tests and correlating the results with patients’ clinicopathological features. Significant overexpression of miRNA-21 was found in breast cancer group. The fold increase in the miR-21 gene expression was significantly higher in circulating exosomes and breast tissues of breast cancer patients as compared to other groups (P < 0.001). Overexpression of miR-21 was also significantly associated with the advanced tumor stage and histological grade. In breast cancer patients, PDCD4 protein expression was decreased to about 70% of the level in the control group. The delta Ct of exosomal and breast tissue miRNA-21 was negatively associated with PDCD4 expression. In conclusion, the translational repression of the PDCD4 induced by the high expression of miR-21 promotes breast cell transformation and development of breast tumor, and circulating miR-21 level could be applied to the screening panels for early detection of women breast cancer.
KeywordsBreast cancer Benign breast lesion Programed death cell 4 MicroRNA-21
Authors would express their sincere appreciation to Professor Robert C. Benjamin, University of North Texas, USA for revising and editing this article prior to submission to the journal.
Professor Dr. NAH has conceived, designed the experiments and share in writing the paper. Dr. MMA has collected the samples, performed the molecular experiments under the supervision of Professor Dr. NAH, contributed reagents/materials/analysis tools and analysed the data. Professor Dr. AGH has performed the immunohistochemical analyses and interpretation of the results.
Compliance with Ethical Standards
Conflict of interest
All authors declare that they have no conflict of interest.
- 1.International Agency for Research on Cancer: Early Detection and Prevention. Globocan 2012. Available from: http://www.iarc.fr/en/research-groups/sec10/index.php. Accessed 13 June 2017.
- 2.Alsaraj M, Alsaed SJ. Iraqi cancer registry 2011. Baghdad: Iraqi Cancer Board, Ministry of Health; 2011. p. 25–38.Google Scholar
- 3.Majid RA, Hassan HA, Muhealdeen DN, Mohammed HA, Hughson MD. Breast cancer in Iraq is associated with a unimodally distributed predominance of luminal type B over luminal type A, surrogates from young to old age. BMC Womens Health. 2017;17:27. https://doi.org/10.1186/s12905-017-0376-0.CrossRefPubMedPubMedCentralGoogle Scholar
- 4.AL-Janabi AA, Naseer ZH, Hamody TA. Epidemiological study of cancers in Iraq-Karbala from 2008 to 2015. Intern J Med Res Health Sci. 2017;6(1):79-86Google Scholar
- 24.Alwan, N. Iraqi initiative of a regional comparative breast cancer research project in the Middle East. J Cancer Biol Res. 2014. Available from: https://www.jscimedcentral.com/CancerBiology/cancerbiology-spidbreastcancer-1016.php. Accessed 13 June 2017.
- 25.AL-wasiti EA, Hasan NA, AL-Salhi AR. Evaluation of markers of oxidative DNA damage in females with breast tumors. Iraqi J Med Sci. 2010;8(1):51–65.Google Scholar
- 26.Abed Oun MA, El-Yssin HD, Al-Alwan NA. Prevalence of soluble fas protein in breast cancer patients: correlation with the clinico-pathological parameter. Iraqi Postgr Med J. 2016;15:107–17.Google Scholar
- 35.De Mattos-Arruda L, Bottai G, Nuciforo PG, Di Tommaso L, Giovannetti E, Peg V, et al. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget. 2015;6(35):37269–80.PubMedPubMedCentralGoogle Scholar
- 39.Hornick N, Huan J, Goloviznina NA, Potter A, Kurre P. Hypoxia regulates exosomal microrna content, trafficking and function of key elements in the AML microenvironment. Blood. 2013. http://www.bloodjournal.org/content/122/21/742. Accessed 13 July 2017.
- 44.Badr FM. Potential role of miR-21 in breast cancer diagnosis and therapy. JSM Biotechnol Bioeng. 2016;3(5):1068.Google Scholar
- 47.Kumar N, Wethkamp N, Waters LC, Carr MD, Klempnauer K-H. Tumor suppressor protein Pdcd4 interacts with Daxx and modulates the stability of Daxx and the Hipk2-dependent phosphorylation of p53 at serine 46. Oncogenesis. 2013;. https://doi.org/10.1038/oncsis.2012.37.CrossRefPubMedPubMedCentralGoogle Scholar
- 51.Qi L, Bart J, Tan LP, Platteel I, Sluis TVD, Huitema S, et al. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer. 2009;9:163. https://doi.org/10.1186/1471-2407-9-163.CrossRefPubMedPubMedCentralGoogle Scholar