Document Type : Research articles

Authors

1 Department of Biology, University Campus 2, University of Guilan, Rasht, Iran

2 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

3 Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.

Abstract

Background: Micro-ribonucleic acids (miRNAs) are noncoding small RNA species considered a varying class with a single-stranded structure whose expression is often dysregulated in cancer. The expression of miRNAs has been used as a promising new biomarker for the detection of breast cancer (BC).  
Objectives: The purpose of the present case-control study was to investigate the expression levels of miRNA-320a and miRNA-497-5p and their potential role in BC patients in comparison to those of the healthy controls in the Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran, in 2019. 
Methods: The concentrations of miR-320a and miR-497-5p were analyzed in 80 serum samples of 40 patients with a confirmed diagnosis of early-stage BC in comparison to those of 40 age-matched healthy volunteers. Real-time quantitative polymerase chain reaction was carried out for the detection of the expression level of these miRNAs.
Results: The results of the current study showed that the serum levels of miR-320a and miR-497-5p were down-regulated in the BC patients, compared to those reported for the healthy controls  (P=0.651 and P=0.044, respectively). However, the levels of miR-320a in the early-stage BC samples were not statistically different from those of the healthy volunteers. There was a reduction in the serum miRNA-320a of the premenopausal subjects under 48 years of age. Serum miRNA-497-5p also decreased among the cases under 48 years of age.
Conclusions: The identification and effectiveness of these miRNAs were demonstrated in the early-stage BC screening. It seems that miRNAs have the potential to be used as biomarkers for the screening and diagnosis of BC.

Keywords

  1. Waks AG, Winer EP. Breast cancer treatment. JAMA. 2019;321(3):316. doi: 10.1001/jama.2018.20751. [PubMed: 30667503].
  2. Wang L. Early diagnosis of breast cancer. Sensors (Basel). 2017;17(7):1572. doi: 10.3390/s17071572. [PubMed: 28678153].
  3. Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004 . doi: 10.1038/sigtrans.2015.4. [PubMed: 29263891].
  4. O'Brien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne). 2018;9:402. doi: 10.3389/fendo.2018.00402. [PubMed: 30123182].
  5. Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci. 2016;17(10):1712. doi: 10.3390/ijms17101712. [PubMed: 27754357].
  6. Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 2012;4(3):143-59. doi: 10.1002/emmm.201100209. [PubMed: 22351564].
  7. Jafarian AH, Kooshkiforooshani M, Farzad F, Mohamadian Roshan N. The Relationship between fibroblastic growth factor receptor-1 (FGFR1) gene amplification in triple negative breast carcinomas and clinicopathological prognostic factors. Iran J Pathol. 2019;14(4):299-304. doi: 10.30699/ijp.2019.96713.1952. [PubMed: 31754359].
  8. Wu X, Ding M, Lin J. Three-microRNA expression signature predicts survival in triple-negative breast cancer. Oncol Lett. 2020;19(1):301-8. doi: 10.3892/ol.2019.11118. [PubMed: 31897142].
  9.  Garzon R, Marcucci G. Potential of microRNAs for cancer diagnostics, prognostication, and therapy. Curr Opin Oncol. 2012;24(6):655-9. doi: 10.1097/CCO.0b013e328358522c. [PubMed: 23079782].
  10. Tie J, Fan D. Big roles of microRNAs in tumorigenesis and tumor development. Histol Histopathol. 2011;26(10):1353-61. doi: 10.14670/HH-26.1353. [PubMed: 21870338].
  11. Ali Syeda Z, Langden SS, Munkhzul C, Lee M, Song SJ. Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci. 2020;21(5):1723. doi: 10.3390/ijms21051723.[PubMed: 32138313].
  12. Baldassarre A, Felli C, Prantera G, Masotti A. Circulating microRNAs and bioinformatics tools to discover novel diagnostic biomarkers of pediatric diseases. Genes (Basel). 2017;8(9):234. doi: 10.3390/genes8090234. [PubMed: 28925938].
  13. Wang B, Yang Z, Wang H, Cao Z, Zhao Y, Gong C, et al. MicroRNA-320a inhibits proliferation and invasion of breast cancer cells by targeting RAB11A. Am J Cancer Res. 2015;5(9):2719-29. [PubMed: 26609479].
  14. Shen L, Li J, Xu L, Ma J, Li H, Xiao X, et al. MiR-497 induces apoptosis of breast cancer cells by targeting Bcl-w. Exp Ther Med. 2012;3(3):475-80. doi: 10.3892/etm.2011.428. [PubMed: 22969914].
  15. Yang H, Yu J, Wang L, Ding D, Zhang L, Chu C, et al. MiR-320a is an independent prognostic biomarker for invasive breast cancer. Oncol Lett. 2014;8(3):1043-50. doi: 10.3892/ol.2014.2298. [PubMed: 25120655].
  16. Lieb V, Weigelt K, Scheinost L, Fischer K, Greither T, Marcou M, et al. Serum levels of miR-320 family members are associated with clinical parameters and diagnosis in prostate cancer patients. Oncotarget. 2017;9(12):10402-16. doi: 10.18632/oncotarget.23781. [PubMed: 29535815].
  17. Luo L, Yang R, Zhao S, Chen Y, Hong S, Wang K, et al. Decreased miR-320 expression is associated with breast cancer progression, cell migration, and invasiveness via targeting Aquaporin 1. Acta Biochimica Biophys Sin (Shanghai). 2018;50(5):473-80. doi: 10.1093/abbs/gmy023. [PubMed: 29538612].
  18. Bai JW, Wang X, Zhang YF, Yao GD, Liu H. MicroRNA-320 inhibits cell proliferation and invasion in breast cancer cells by targeting SOX4. Oncol Lett. 2017;14(6):7145-52. doi: 10.3892/ol.2017.7087. [PubMed: 29344145].
  19. Zhang T, Zou P, Wang T, Xiang J, Cheng J, Chen D, et al. Down-regulation of miR-320 associated with cancer progression and cell apoptosis via targeting Mcl-1 in cervical cancer. Tumour Biol. 2016;37(7):8931-40. doi: 10.1007/s13277-015-4771-6. [PubMed: 26753959].
  20. Liu Z, Wu S, Wang S, Kang S, Zhao B, He F, et al. Prognostic value of microRNA-497 in various cancers: a systematic review and meta-analysis. Dis Markers. 2019;2019:2491291. doi: 10.1155/2019/2491291. [PubMed: 31191744].
  21. Hou H, Gong L, Zhou L, Qin H, Mei X, Xie Y, et al. The potential role of microRNA-497 in different cancers. Int J Clin Exp Pathol. 2016;9(8):7813-8.
  22. Wu Z, Cai X, Huang C, Xu J, Liu A. MiR-497 suppresses angiogenesis in breast carcinoma by targeting HIF-1α. Oncol Rep. 2016;35(3):1696-702. doi: 10.3892/or.2015.4529. [PubMed: 26718330].
  23. Heydari N, Nikbakhsh N, Sadeghi F, Farnoush N, Khafri S, Bastami M, et al. Overexpression of serum microRNA-140-3p in premenopausal women with newly diagnosed breast cancer. Gene. 2018;655:25-9. doi: 10.1016/j.gene.2018.02.032. [PubMed: 29474861].
  24. Nashtahosseini Z, Aghamaali MR, Sadeghi F, Heydari N, Parsian H. Circulating status of microRNAs 660‐5p and 210‐3p in breast cancer patients. J Gene Med. 2021;23(4):e3320. doi: 10.1002/jgm.3320. [PubMed: 33533518].
  25. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):e45. doi: 10.1093/nar/29.9.e45. [PubMed: 11328886].
  26. Wang H, Peng R, Wang J, Qin Z, Xue L. Circulating microRNAs as potential cancer biomarkers: the advantage and disadvantage. Clin Epigenetics. 2018;10:59. doi: 10.1186/s13148-018-0492-1. [PubMed: 29713393].
  27. Lindner K, Haier J, Wang Z, Watson DI, Hussey DJ, Hummel R, et al. Circulating microRNAs: emerging biomarkers for diagnosis and prognosis in patients with gastrointestinal cancers. Clin Sci (Lond). 2015;128(1):1-15. doi: 10.1042/CS20140089. [PubMed: 25168167].
  28. Yan LX, Huang XF, Shao Q, Huang MY, Deng L. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008;14(11):23-60. doi: 10.1261/rna.1034808. [PubMed: 18812439].
  29. Chang YY, Kuo WH, Hung JH, Lee CY, Lee YH, Chang YC, et al. Deregulated microRNAs in triple-negative breast cancer revealed by deep sequencing. Mol Cancer. 2015;14:36. doi: 10.1186/s12943-015-0301-9. [PubMed: 25888956].
  30. Shen L, Li J, Xu L, MA J, LI H, Xiao X, et al. miR-497 induces apoptosis of breast cancer cells by targeting Bcl-w. Exp Ther Med. 2012;3(3):475-80. doi: 10.3892/etm.2011.428. [PubMed: 22969914].
  31. Luo Q, Li X, Gao Y, Long Y, Chen L, Huang Y, et al. MiRNA-497 Regulates cell growth and invasion by targeting cyclin E1 in breast cancer. Cancer Cell Int. 2013;13:95. doi: 10.1186/1475-2867-13-95. [PubMed: 24112607].
  32. Du M, Shi D, Yuan L, Li P, Chu H. Circulating miR-497 and miR-663b in plasma are potential novel biomarkers for bladder cancer. Sci Rep. 2013;5:10437. doi: 10.1038/srep10437. [PubMed: 26014226].
  33. Luo M, Shen, D, Zhou, X, Chen, X, Wang W. MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor. Surgery. 2013;153(6):836–47. doi: 10.1016/j.surg.2012.12.004. [PubMed: 23453369].