THE INFLUENCE OF RADIOTHERAPY ON CIRCULATING miRNA EXPRESSION LEVELS AND HEMORHEOLOGICAL PROPERTIES IN PROSTATE CANCER

Year 2017, Volume: 3 Issue: 1, 42 - 49, 30.03.2017

Nazlı Eyvan Topçu Özden Fatma Behice Cinemre Hakan Cinemre Selim Ögüt Nurten Bahtiyar Didem Karaçetin Haldun Şükrü Erkal Birsen Aydemir

Abstract

Background: In prostate cancer, radiotherapy has therapeutic
effect and increase treatment efficacy and thus the survival rate. However
radio-resistant tumors may relapse and metastases. In cancer cells, some genes
effected by radiation has direct effects on results of radiotherapy. MikroRNAs
(miRNAs) are the molecules which regulate some processes related with internal
and external stresses. It has been showed that radiation resulted in some
changes on synthesis of miRNAs and so, cellular responses in tumor cells. The
aim of our study was to investigate expression levels of miR-20a and miR-106b
and some biochemical parameters, and plasma viscosity in patients with prostate
cancer, before and after radiotherapy.

Materials
and Methods: 35 patients
who admitted to Radiation Oncology Department for prostat cancer radiotherapy
were included in this study. Blood samples were obtained before and after
radiotherapy. miR-20a and miR-106b expressions were analyzed by using
quantitative reverse-transcription polymerase chain reaction (qRT-PZR). Plasma
viscosity values were measured by using Harkness capillary viscometer. Blood
albumin and total protein levels were analyzed by autoanalyser system.
Leukocyte, lymphocyte, erythrocyte, platelet and neutrophil counts were
measured by automatic cell counter.

Results:
We found that miR-20a
and miR-106b expression levels, and plasma viscosity values increased in the
patients after radiotherapy. We also found that erythrocyte and platelet
counts, albumin and total protein levels did not significantly change while PSA,
fPSA, leukocyte, lymphocyte and neutrophil counts significantly decreased in
patients after radiation treatment. From Pearson’s rank correlation analysis, we
found that miR-20a expression levels positively correlated with miR-106b
expression levels after radiotherapy group (r=0.722, p=0.01). The levels of
fPSA correlated significantly with miR-106b expression levels before
radiotherapy group (r=-0.598, p=0.014). Additionally, the leukocyte count
correlated significantly with miR-20a expression levels before radiotherapy
group (r=−0.474, p=0.035).  

 

 

 

 

 

Conclusion: Our findings showed that expression levels of some
miRNAs such as miR-20a and miR-106b and hemorheological parameters were changed in prostate cancer patient after
radiation treatment. These changes might be an important factor for cancer treatment
and metastasis. Effects of these changes on prostate cancer patients must be
clarified with further studies. 

Keywords

Radiotherapy, prostate cancer, miR-20a, miR-106b, plasma viscosity

References

• 1. Mu P, Deng S, Fan X. MicroRNAs in Prostate Cancer: Small RNAs with Big Roles. J Clin Cell Immunol 2015; 6: 315.
• 2. Vakifahmetoglu H, Olsson M, Zhivotovsky B. Death through a tragedy: Mitotic catastrophe. Cell Death Differ 2008; 15: 1153–62.
• 3. Willers H, Held KD. Introduction to clinical radiation biology. Hematol Oncol Clin North Am 2006; 20: 1–24.
• 4. Li L, Story M, Legerski RJ. Cellular responses to ionizing radiation damage. Int J Radiat Oncol Biol Phys 2001; 49:1157–62.
• 5. Steel GG. From targets to genes: a brief history of radiosensitivity. Phys Med Biol 1996; 41:205–22.
• 6. Metheetrairut C, Slack FJ. MicroRNAs in the Ionizing Radiation Response and in Radiotherapy. Curr Opin Genet Dev. 2013; 23(1):12–9.
• 7. Leung CH, Li SC, Chen TW. et al. Comprehensive microRNA profiling of prostate cancer cells after ionizing radiation treatment. Oncol Reports 2014; 31: 1067-78.
• 8. Li B, Shi XB, Nori D, et al: Down-regulation of microRNA 106b is involved in p21-mediated cell cycle arrest in response to radiation in prostate cancer cells. Prostate 2011; 71: 567-74.
• 9. Sylvestre Y, De Guire V, Querido E, Mukhopadhyay UK, Bourdeau V, Major F, Ferbeyre G and Chartrand P: An E2F/miR- 20a autoregulatory feedback loop. J Biol Chem. 2007; 282(4): 2135- 43.
• 10. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006; 103(7): 2257-61.
• 11. Pesta M, Klecka J, Kulda V, et al. Importance of miR-20a expression in prostate cancer tissue. Anticancer Res 2010; 30(9):3579-83.
• 12. Fliedner TM, Graessle DH. Hemopoeitic response to low dose-rates of ionizing radiation shows stem cell tolerance and adaptation. Dose Response 2012; 10: 644-63.
• 13. Dainiak N, Sorba S. Early identification of radiation accident victims for therapy of bone marrow failure. Stem Cells 1997; 15: 275-85.
• 14. Smirnova OA. Environmental Radiation Effects on Mammals-A Dynamical Modeling Approach. NY, USA Springer 2010; 23: 12-9.
• 15. Edwards G. Health and Environmental Issues Linked to the Nuclear Fuel Chain. Canadian Environmental Advisory Council. 1977. http://www.ccnr.org/ceac_A.html.)
• 16. International Committee for Standardization in Heamatology (ICSH). Recommendation for a selected method for the measurement of plasma viscosity. J Clin Pathol. 1984; 37: 1147–52.
• 17. Barutcu UB, Akyolcu MC, Toplan S, et al. Effects of coronary artery diseases on haemorheological parameters and trace elements. J Basic Clin Physiol Pharmacol 1995; 6: 289–94.
• 18. Runkle EA, Zhang H, Cai Z, et al: Reversion of the ErbB malignant phenotype and the DNA damage response. Exp Mol Pathol 2012; 93: 324-33.
• 19. Zhao L, Bode AM, Cao Y, Dong Z. Regulatory mechanisms and clinical perspectives of miRNA in tumor radiosensitivity. Carcinogenesis 2012; 33:2220-27.
• 20. Zhao L, Lu X, Cao Y. MicroRNA and signal transduction pathways in tumor radiation response. Cell Signal 2013; 25:1625-34.
• 21. John-Aryankalayil M, Palayoor ST, Makinde AY, et al: Fractionated radiation alters oncomir and tumor suppressor miRNAs in human prostate cancer cells. Radiat Res. 2012; 178: 105-17.