Abstract
Some microRNAs are usually dysregulated in the cancers and influencing tumor behavior and progression. Hsa-miR-181b-1 and its target CYLD are involved in regulating the inflammatory pathways. This study aimed to investigate the expression levels of hsa-mir-181b-1 and CYLD in a cohort of breast tumor tissues and normal adjacent tissues to assess their association with breast cancer stages. A total number of 60 breast samples including cancerous and normal adjacent tissue specimens were collected. After pathological study, the expression of hsa-mir-181b-1 and CYLD were measured by qRT-PCR method. The hsa-mir-181b-1 expression level was significantly increased in breast tumor tissues compared to the controls. This increase was associated with the disease progression. Conversely, CYLD expression level was decreased in tumor samples compared to normal samples, significantly. ROC curve data added other prestigious information of hsa-mir-181b-1 and CYLD by defining cancer and healthy tissues with high specificity and sensitivity at a proposed cutoff point. Also, bioinformatic enrichment for the possible targets of mature sequence of “hsa-mir-181b-5p” was performed. Computational analysis showed the five most significant pathways including metabolic, cancer, calcium signaling, PI3K–Akt signaling and focal adhesion pathways which may be influenced by hsa-mir-181b-1. Thus, we suggested hsa-mir-181b-1 and CYLD might be involved in the pathogenesis of breast cancer and could be considered as two biomarkers for prediction, prognosis and diagnosis of the stages of the breast cancer.
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Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell. 2010;39(4):493–506.
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834.
Liu J, Shi W, Wu C, Ju J, Jiang J. MiR-181b as a key regulator of the oncogenic process and its clinical implications in cancer. Biomed Rep. 2014;2(1):7–11.
Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA. 2008;14:2348–60.
Andorfer CA, Necela BM, Thompson EA, Perez EA. MicroRNA signatures: clinical biomarkers for the diagnosis and treatment of breast cancer. Trends Mol Med. 2011;17(6):313–9.
Rouigari M, Dehbashi M, Tabatabaeian H, Ghaedi K, Mohammadynejad P, Azadeh M. Evaluation of the expression level and hormone receptor association of miR-126 in breast cancer. Indian J Clin Biochem. 2018. https://doi.org/10.1007/s12291-018-0766-6
Li D, Jian W, Wei C, Song H, Gu Y, Luo Y, et al. Down-regulation of miR-181b promotes apoptosis by targeting CYLD in thyroid papillary cancer. Int J Clin Exp Pathol. 2014;7(11):7672.
Shostak K, Chariot A. NF-κB, stem cells and breast cancer: the links get stronger. Breast Cancer Res. 2011;13(4):214.
Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z, et al. Hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 2008;1236:185–93.
Zanette DL, Rivadavia F, Molfetta GA, Barbuzano FG, Proto-Siqueira R, Silva WA Jr, et al. miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res. 2007;40(11):1435–40.
Ren Y, Gao J, Liu JQ, Wang XW, Gu JJ, Huang HJ, et al. Differential signature of fecal microRNAs in patients with pancreatic cancer. Mol Med Rep. 2012;6(1):201–9.
Nurul-Syakima Α, Yoke-Kqueen C, Sabariah A, Shiran M, Singh A, et al. Differential microRNA expression and identification of putative miRNA targets and pathways in head and neck cancers. Int J Mol Med. 2011;28(3):327–36.
Ratert N, Meyer HA, Jung M, Mollenkopf HJ, Wagner I, Miller K, et al. Reference miRNAs for miRNAome analysis of urothelial carcinomas. PLoS ONE. 2012;7(6):e39309.
Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, et al. MiRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 2011;9(7):824–33.
Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, et al. Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 2010;126(5):1166–76.
Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, et al. MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J Clin Investig. 2012;122(6):1973–90.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18–43.
Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005;334(4):1351–8.
Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, et al. Prognostic values of microRNAs in colorectal cancer. Biomark Insights. 2006;2:113–21.
Jiang J, Zheng X, Xu X, Zhou Q, Yan H, Zhang X, et al. Prognostic significance of miR-181b and miR-21 in gastric cancer patients treated with S-1/oxaliplatin or doxifluridine/oxaliplatin. PLoS ONE. 2011;6(8):e23271.
Wu L, Lin Q, Shi J, Lin X. Evaluation of miR-182/miR-100 ratio for diagnosis and survival prediction in bladder cancer. Arch Iran Med. 2016;19(9):645.
Conti A, Aguennouz M, La Torre D, Tomasello C, Cardali S, Angileri FF, et al. MiR-21 and 221 upregulation and miR-181b downregulation in human grade II–IV astrocytic tumors. J Neurooncol. 2009;93(3):325–32.
Xu DD, Zhou PJ, Wang Y, Zhang L, Fu WY, Ruan BB, et al. Reciprocal activation between STAT3 and miR-181b regulates the proliferation of esophageal cancer stem-like cells via the CYLD pathway. Mol Cancer. 2016;15(1):40.
Ghadami E, Nikbakhsh N, Fattahi S, Kosari-Monfared M, Ranaee M, Taheri H, et al. Epigenetic alterations of CYLD promoter modulate its expression in gastric adenocarcinoma: a footprint of infections. J Cell Physiol. 2019;234(4):4115–24.
Kinoshita H, Okabe H, Beppu T, Chikamoto A, Hayashi H, Imai K, et al. CYLD downregulation is correlated with tumor development in patients with hepatocellular carcinoma. Mol Clin Oncol. 2013;1(2):309–14.
Hutti JE, Shen RR, Abbott DW, Zhou AY, Sprott KM, Asara JM, et al. Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKKepsilon promotes cell transformation. Mol Cell. 2009;34(4):461–72.
Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006;103(7):2257–61.
Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007;297(17):1901–8.
Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology. 2009;50(2):472–80.
Wang F, Sun JY, Zhu YH, Liu NT, Wu YF, Yu F. MicroRNA-181 inhibits glioma cell proliferation by targeting cyclin B1. Mol Med Rep. 2014;10(4):2160–4. https://doi.org/10.3892/mmr.2014.2423
Huang P, Ye B, Yang Y, Shi J, Zhao H. MicroRNA-181 functions as a tumor suppressor in non-small cell lung cancer (NSCLC) by targeting Bcl-2. Tumor Biol. 2015;36(5):3381–7.
Tong SJ, Liu J, Wang X, Qu LX. MicroRNA-181 promotes prostate cancer cell proliferation by regulating DAX-1 expression. Exp Ther Med. 2014;8(4):1296–300.
Sun Y, Yu S, Liu Y, Wang F, Liu Y, Xiao H. Expression of miRNAs in papillary thyroid carcinomas is associated with BRAF mutation and clinicopathological features in Chinese patients. Int J Endocrinol. 2013;2013.
Salaun B, Yamamoto T, Badran B, Tsunetsugu-Yokota Y, Roux A, Baitsch L, et al. Differentiation associated regulation of microRNA expression in vivo in human CD8+ T cell subsets. J Transl Med. 2011;9(1):44.
Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 2006;13(2):497–508.
Peng J, Thakur A, Zhang S, Dong Y, Wang X, Yuan R, et al. Expressions of miR-181a and miR-20a in RPMI8226 cell line and their potential as biomarkers for multiple myeloma. Tumor Biol. 2015;36(11):8545–52.
Acknowledgements
The authors would like to thank for the Cancer Institute of Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran for providing the clinical samples and also for the graduate offices of Tehran University of Medical Sciences and Isfahan University of Medical Sciences for their financial supports (Grant No. 192046).
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Andalib, A., Rashed, S., Dehbashi, M. et al. The Upregulation of hsa-mir-181b-1 and Downregulation of Its Target CYLD in the Late-Stage of Tumor Progression of Breast Cancer. Ind J Clin Biochem 35, 312–321 (2020). https://doi.org/10.1007/s12291-019-00826-z
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DOI: https://doi.org/10.1007/s12291-019-00826-z