Murat DEMİR, Osman ERGÜN, Alim KOŞAR, Muhammet Yusuf TEPEBAŞI, Pınar ASLAN KOŞAR, Okan SANCER

Determination of miRNA expression profile in patients with prostate cancer and benign prostate hyperplasia

Background/aim: It is a known fact that the role of microRNAs (miRNA) has a very important place in cancer development and progression. miRNAs target a significant part of pathways as well as genes. This study aimed to compare the differential expression profiles of miRNAs in prostate cancer and benign prostatic hyperplasia patients. Materials and methods: Peripheral blood mononuclear cells (PBMCs) and tissue samples were collected from prostate cancer (PCa) (n:20) and benign prostatic hyperplasia (BPH) (n: 20) patients. Total RNA isolation was performed. As a result of the RNA concentration and purity measurement, each patient group was pooled, and the miRNAs profiles comparison was performed with the Affymetrix Microarray System. Results: In tissue samples, 37 different expressed miRNAs were identified in PCa patients compared to BPH patients. In PBMCs samples, 27 different expressed miRNAs were identified in PCa patients compared to benign prostatic hyperplasia patients. As a result of the comparison of tissue and PBMCs samples, it was determined that down regülated hsa-miR-494-3p, hsa-miR-3128, hsa-miR-8084 were common miRNAs. 3 (HIF1A, NHS,INSL4) targets identified for hsa-miR-494-3p, 2 (HIF1A, AVRP1A) for hsa-miR-3128, 3 (AVRP1A, NHS, INSL4) for hsa-miR-8084. Conclusion: Our results suggested that determined common hsa-miR-494-3p, hsa-miR-3128, hsa-miR-8084 and their target HIF1A, AVRP1A, NHS, INSL4 may play a crucial role in therapeutic and early diagnostic strategies for prostate cancer. The present study may represent the first in-depth analysis of PBMCs and tissue samples miRNA profiles.

PDF

___

1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin D et al. Estimating the global cancer incidence and mortality in 2018: Globocan sources and methods. International Journal of Cancer. 2019; 144 (8): 1941-1953. doi: 10.1002/ijc.31937
2. Wong MC, Goggins WB, Wang HH, Fung FD, Leung C et al. Global incidence and mortality for prostate cancer: analysis of temporal patterns and trends in 36 countries. European Urology. 2016; 70 (5): 862-874. doi: 10.1371/journal.pone.0221775
3. Hatcher D, Garrett Daniels IO, Lee P. Molecular mechanisms involving prostate cancer racial disparity. American Journal of Translational Research. 2009; 1 (3): 235.
4. Krasanakis T, Nikolouzakis TK, Sgantzos M, Mariolis-Sapsakos T, Souglakos J et al. Role of anabolic agents in colorectal carcinogenesis: myths and realities. Oncology reports. 2019; 42 (6): 2228-2244. doi: 10.3892/or.2019.7351
5. Mettlin C, Lee F, Drago J, Murphy GP. Project IotACSNPCD: The American cancer society national prostate cancer detection project. Findings on the detection of early prostate cancer in 2425 men. Cancer. 1991; 67 (12): 2949- 2958. doi: 10.1002/1097-0142(19910615)67:12<2949::aidcncr2820671202>3.0.co;2-x
6. Prestigiacomo A, Stamey T. Clinical usefulness of free and complexed PSA. Scandinavian Journal of Clinical and Laboratory Investigation 1995; 55 (221): 32-34. doi: 10.3109/00365519509090561
7. Morote J, Lopez M, Encabo G, De Torres I. Effect of inflammation and benign prostatic enlargement on total and percent free serum prostatic specific antigen. European Urology. 2000; 37 (5): 537-540. doi: 10.1159/000020190
8.Smith DK, Natasha Venugopal, Martha K. Terris, Bal L. Lokeshwar. The critical role of interleukin-8 chemokine axis in the development of benign prostatic hyperplasia (BPH). In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; Atlanta, GA, USA. pp. 123.
9. Jarvis TR, Chughtai B, Kaplan SA. Testosterone and benign prostatic hyperplasia. Asian Journal of Andrology. 2015; 17 (2): 212. doi: 10.4103/1008-682X.140966
10. Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Medical Clinics. 2011; 95 (1): 87-100. doi: 10.1016/j.mcna.2010.08.013
11. Ma J, Lin Y, Zhan M, Mann DL, Stass SA et al. Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer. Laboratory Investigation. 2015; 95 (10):1197-1206. doi: 10.1038/labinvest.2015.88
12. Chen S, Liu M, Liang B, Ge S, Peng J et al. Identification of human peripheral blood monocyte gene markers for early screening of solid tumors. PloS One. 2020; 15 (3): e0230905. doi: 10.1371/ journal.pone.0230905
13. Jung SH, Young SS. Power and sample size calculation for microarray studies. Journal of Biopharmaceutical Statistics. 2012; 22 (1): 30-42. doi: 10.1080/10543406.2010.500066
14. Lin WJ, Hsueh HM, Chen JJ. Power and sample size estimation in microarray studies. BMC Bioinformatics. 2010; 11 (1): 1-9. doi: 10.1186/1471-2105-11-48
15. Huang W, Kang XL, Cen S, Wang Y, Chen X. High-level expression of microRNA-21 in peripheral blood mononuclear cells is a diagnostic and prognostic marker in prostate cancer. Genetic Testing and Molecular Biomarkers. 2015; 19 (9): 469- 475. doi: 10.1089/gtmb.2015.0088
16. Gungormez C, Aktas HG, Dilsiz N, Borazan E. Novel miRNAs as potential biomarkers in stage II colon cancer: microarray analysis. Molecular Biology Reports. 2019; 46 (4): 4175-4183. doi: 10.1007/s11033-019-04868-7
17. Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS et al. Prostatespecific antigen as a serum marker for adenocarcinoma of the prostate. New England Journal of Medicine. 1987; 317 (15): 909-916. doi: 10.1056/NEJM198710083171501
18. Stephan C, Stroebel G, Heinau M, Lenz A, Roemer A. The ratio of prostate‐specific antigen (PSA) to prostate volume (PSA density) as a parameter to improve the detection of prostate carcinoma in PSA values in the range of< 4 ng/mL. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2005; 104 (5): 993-1003. doi: 10.1002/cncr.21267
19. Richardsen E, Andersen S, Melbø-Jørgensen C, Rakaee M, Ness N et al. MicroRNA 141 is associated to outcome and aggressive tumor characteristics in prostate cancer. Scientific Reports. 2019; 9 (1): 1-9. doi: 10.1038/s41598-018-36854-7
20. Cai B, Peng JH. Increased Expression of miR-494 in Serum of Patients with Prostate Cancer and its Potential Diagnostic Value. Clinical Laboratory. 2019; 65 (8). doi: 10.7754/Clin. Lab.2019.190422
21. Luo J, Guo Y, Liu X, Yang X, Xiao F et al. Long non-coding RNA LINC01410 promotes colon cancer cell proliferation and invasion by inhibiting miR-3128. Experimental and Therapeutic Medicine. 2018; 16 (6): 4824-4830. doi: 10.3892/ etm.2018.6806
22. Gao Y, Ma H, Gao C, Lv Y, Chen X et al. Tumor-promoting properties of miR-8084 in breast cancer through enhancing proliferation, suppressing apoptosis and inducing epithelial– mesenchymal transition. Journal of translational medicine 2018, 16(1):1-13. doi: 10.1186/s12967-018-1419-5
23. Liu K, Liu S, Zhang W, Jia B, Tan L et al. miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN. Oncology Reports. 2015; 34 (2): 1003-1010. doi: 10.3892/ or.2015.4030
24. Lin H, Huang ZP, Liu J, Qiu Y, Tao YP et al. miR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN. Scientific Reports. 2018; 8 (1): 1-9. doi: 10.1038/s41598-018-28519-2
25. Lu Q, Liu T, Feng H, Yang R, Zhao X et al. Circular RNA circSLC8A1 acts as a sponge of miR-130b/miR-494 in suppressing bladder cancer progression via regulating PTEN. Molecular Cancer. 2019; 18 (1): 1-13. doi: 10.1186/s12943-019- 1040-0
26. Li L, Li Z, Kong X, Xie D, Jia Z et al. Down-regulation of microRNA-494 via loss of SMAD4 increases FOXM1 and β-catenin signaling in pancreatic ductal adenocarcinoma cells. Gastroenterology. 2014; 147 (2): 485-497. doi: 10.1053/j. gastro.2014.04.048
27. Xu Q, He L, Ma L, Fan L, Yan L et al. LINC01410 accelerated the invasion and proliferation of osteosarcoma by sponging miR3128. Aging (Albany NY). 2020; 12 (24): 24957–24966. doi: 10.18632/aging.103464
28. Zhao L, Zhang X, Guo H, Liu M, Wang L. LOXL1-AS1 contributes to non-small cell lung cancer progression by regulating miR3128/RHOXF2 Axis. OncoTargets and Therapy. 2020; 13: 6063–6071. doi: 10.2147/OTT.S247900
29. Chong GO, Jeon HS, Han HS, Son JW, Lee YH et al. Differential microRNA expression profiles in primary and recurrent epithelial ovarian cancer. Anticancer Research. 2015; 35 (5): 2611-2617
30. Tran MG, Bibby BA, Yang L, Lo F, Warren AY et al. Independence of HIF1a and androgen signaling pathways in prostate cancer. BMC Cancer. 2020; 20: 1-12. doi: 10.1186/s12885-020-06890-6
31. Ivell R, Agoulnik AI, Anand‐Ivell R. Relaxin‐like peptides in male reproduction–a human perspective. British Journal of Pharmacology. 2017, 174 (10): 990-1001. doi: 10.1111/ bph.13689
32. Zhao N, Peacock SO, Lo CH, Heidman LM, Rice MA et al. Arginine vasopressin receptor 1a is a therapeutic target for castration-resistant prostate cancer. Science Translational Medicine. 2019; 11 (498): eaaw4636. doi: 10.1126/scitranslmed. aaw4636
33. Fenner A. AVPR1A: a target in CRPC? Nature Reviews Urology. 2019; 16 (9): 508. doi:10.1038/s41585-019-0218-y
34. Hernández V, Pascual Camps I, Aparisi M, Martínez Matilla M, Martínez F et al. Great clinical variability of Nance Horan syndrome due to deleterious NHS mutations in two unrelated Spanish families. Ophthalmic Genetics. 2019; 40 (6): 553-557. doi: 10.1080/13816810.2019.1692362
35. Brooks SP, Coccia M, Tang HR, Kanuga N, Machesky LM et al. The Nance–Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology. Human Molecular Genetics. 2010; 19 (12): 2421-2432. doi: 10.1093/ hmg/ddq125