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Micro RNA 34a and Let-7a Expression in Human Breast Cancers is Associated with Apoptotic Expression Genes

  • Behzad, Mansoori (Immunology Research Center, Tabriz University of Medical Sciences) ;
  • Ali, Mohammadi (Immunology Research Center, Tabriz University of Medical Sciences) ;
  • Solmaz, Shirjang (Immunology Research Center, Tabriz University of Medical Sciences) ;
  • Elham, Baghbani (Immunology Research Center, Tabriz University of Medical Sciences) ;
  • Behzad, Baradaran (Immunology Research Center, Tabriz University of Medical Sciences)
  • Published : 2016.06.01

Abstract

Breast cancer is the most common cause of cancer-related death among women in the whole world. MiR- 34a and let-7a are well known tumor suppressors that participate in the regulation of apoptosis, invasion and other cellular functions. In this study, expression of miR-34a, let-7a and apoptosis pathway genes such as Bcl-2, Caspase-3 and P53 were evaluated using quantitative real-time PCR in 45 paired samples of normal margin and tumor tissue collected from breast cancer patient at advanced stage (3-4). MiR-34a, let-7a, caspase-3 and P53 expression are reduced and Bcl-2 expression is increased within tumoral tissues in comparison with normal margin tissues. P53 expression directly or indirectly was correlated with miR-34a, let-7a, Bcl-2 and caspase-3 expression. In This study we found that MiR-34a and let-7a expression are reduced in the tumoral tissues. Down-regulation of these two molecules correlated with expression of genes associated with apoptosis. These results suggest that due to the correlation of miR-34a and let-7a with apoptotic and anti-apoptotic pathways these molecules could participate as regulators in advanced clinical stages of breast cancer and should be considered as markers for diagnosis, prognostic assessment and targeted therapy.

Keywords

References

  1. Bussing I, Slack FJ, Grosshans H (2008). let-7 microRNAs in development, stem cells and cancer. Trends Molecular Med, 14, 400-9. https://doi.org/10.1016/j.molmed.2008.07.001
  2. Chou J, Shahi P, Werb Z (2013). microRNA-mediated regulation of the tumor microenvironment. Cell Cycle, 12, 3262-71. https://doi.org/10.4161/cc.26087
  3. Costa PM, Pedroso de Lima MC (2013). MicroRNAs as molecular targets for cancer therapy: on the modulation of microRNA expression. Pharmaceuticals, 6, 1195-220. https://doi.org/10.3390/ph6101195
  4. Davis S, Lollo B, Freier S, et al (2006). Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res, 34, 2294-304. https://doi.org/10.1093/nar/gkl183
  5. Fang Y, Gao W (2014). Roles of microRNAs during prostatic tumorigenesis and tumor progression. Oncogene, 33, 135-47. https://doi.org/10.1038/onc.2013.54
  6. Fridman JS, Lowe SW (2003). Control of apoptosis by p53. Oncogene, 22, 9030-40. https://doi.org/10.1038/sj.onc.1207116
  7. Garzon R, Calin GA, Croce CM (2009). MicroRNAs in cancer. Annual Review Med, 60, 167-79. https://doi.org/10.1146/annurev.med.59.053006.104707
  8. Giono LE, Manfredi JJ (2006). The p53 tumor suppressor participates in multiple cell cycle checkpoints. J Cellular Physiol, 209, 13-20. https://doi.org/10.1002/jcp.20689
  9. Hannafon BN, Sebastiani P, de las Morenas A, et al (2011). Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer. Breast Cancer Res, 13, 24.
  10. Iorio MV, Casalini P, Tagliabue E, et al (2008). MicroRNA profiling as a tool to understand prognosis, therapy response and resistance in breast cancer. Eur J Cancer, 44, 2753-9. https://doi.org/10.1016/j.ejca.2008.09.037
  11. Kumar MS, Erkeland SJ, Pester RE, et al (2008). Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci USA, 105, 3903-8. https://doi.org/10.1073/pnas.0712321105
  12. Mansoori B, Mohammadi A, Shirjang S, et al (2014). Micro- RNAs: The new potential biomarkers in cancer diagnosis, prognosis and cancer therapy. Cellular Molecular Biol, 61, 1-10.
  13. Ong CC, Gierke S, Pitt C, et al (2015). Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents. Breast Cancer Res, 17, 59. https://doi.org/10.1186/s13058-015-0564-5
  14. Peltier HJ, Latham GJ (2008). Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA, 14, 844-52. https://doi.org/10.1261/rna.939908
  15. Reis LO, Pereira TC, Lopes-Cendes I, et al (2010). MicroRNAs: a new paradigm on molecular urological oncology. Urol, 76, 521-7. https://doi.org/10.1016/j.urology.2010.03.012
  16. Shi X-B, Tepper CG, deVere White RW (2008). Cancerous miRNAs and their regulation. Cell Cycle, 7, 1529-38. https://doi.org/10.4161/cc.7.11.5977
  17. Thun MJ, DeLancey JO, Center MM, et al (2010). The global burden of cancer: priorities for prevention. Carcinogenesis, 31, 100-10. https://doi.org/10.1093/carcin/bgp263
  18. Yao Y, Hu J, Shen Z, et al (2015). MiR 200b expression in breast cancer: a prognostic marker and act on cell proliferation and apoptosis by targeting Sp1. J Cellular Molecular Med, 19, 760-9. https://doi.org/10.1111/jcmm.12432
  19. Yu F, Yao H, Zhu P, et al (2007). let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell, 131, 1109-23. https://doi.org/10.1016/j.cell.2007.10.054
  20. Zenz T, Mohr J, Eldering E, et al (2009). miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood, 113, 3801-8. https://doi.org/10.1182/blood-2008-08-172254
  21. Zhang D-G, Zheng J-N, Pei D-S (2014). P53/microRNA- 34-induced metabolic regulation: new opportunities in anticancer therapy. Molecular Cancer, 13, 1-7. https://doi.org/10.1186/1476-4598-13-1

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