Abstract
Breast carcinoma is a heterogeneous disease that affects millions of women worldwide. Wilms’ tumor 1 (WT1) is an oncogene that promotes proliferation, metastasis and reduces apoptosis. MicroRNAs (miR) are short noncoding RNAs with a major role in cancer metastasis. In present study, we investigated the association of serum level of WT1 with oxidative stress and expression of miR-361-5p in breast cancer. Serum samples of 45 patients and of 45 healthy women analyzed for protein level of WT1, malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant capacity (TAC). Serum and tissue expression of miR-361-5p in 45 tumor tissues and 45 paired non-tumor adjacent tissues and 45 serum samples of patients and healthy women analyzed by qRT-PCR. Protein levels of WT1 not significantly difference in serum of patients compared to healthy controls. Serum levels of MDA and TOS in patients were higher, but TAC level was lower than healthy controls (p < 0.001). There was a positive correlation between WT1 with MDA and TOS, and a negative correlation between WT1 with TAC in patients. miR-361-5p expression in tumor tissues and serum of patients was lower than non-tumor adjacent tissues and serum of healthy controls, respectively (p < 0.001). Moreover, there was a negative correlation between miR-361-5p and WT1 in patients. The positive correlation between WT1 with MDA and TOS and negative correlation between TAC and miR-361-5p suggests that this gene can play an important role in worse prognoses in breast cancer. Additionally, miR-361-5p may serve as an invasive biomarker for early detection of breast cancer.
Similar content being viewed by others
Data Availability
The datasets analyzed during the current study are available from the corresponding author on reasonable request.
References
Xie F, Hosany S, Zhong S, Jiang Y, Zhang F, Lin L, et al. MicroRNA-193a inhibits breast cancer proliferation and metastasis by downregulating WT1. PLoS ONE. 2017;12(10):e0185565.
Cominetti MR, Altei WF, Selistre-de-Araujo HS. Metastasis inhibition in breast cancer by targeting cancer cell extravasation. Breast Cancer: Targets and Therapy. 2019;11:165.
Hastie ND. Wilms’ tumour 1 (WT1) in development, homeostasis and disease. Development. 2017;144(16):2862–72.
Nasomyon T, Samphao S, Sangkhathat S, Mahattanobon S, Graidist P. Correlation of Wilms’ tumor 1 isoforms with HER2 and ER-α and its oncogenic role in breast cancer. Anticancer Res. 2014;34(3):1333–42.
Artibani M, Sims AH, Slight J, Aitken S, Thornburn A, Muir M, et al. WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel. Sci Rep. 2017;7:45255.
Scholz H, Kirschner KM. Oxygen-dependent gene expression in development and cancer: lessons learned from the Wilms’ tumor gene, WT1. Front Mol Neurosci. 2011;4:4.
Brown NS, Bicknell R. Hypoxia and oxidative stress in breast cancer Oxidative stress-its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res. 2001;3(5):1–5.
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.
Thakur S, Grover RK, Gupta S, Yadav AK, Das BC. Identification of specific miRNA signature in paired sera and tissue samples of Indian women with triple negative breast cancer. PLoS ONE. 2016;11(7):e0158946.
Pescador N, Pérez-Barba M, Ibarra JM, Corbatón A, Martínez-Larrad MT, Serrano-Ríos M. Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers. PLoS ONE. 2013;8(10):e77251.
Ma F, Song H, Guo B, Zhang Y, Zheng Y, Lin C, et al. MiR-361-5p inhibits colorectal and gastric cancer growth and metastasis by targeting staphylococcal nuclease domain containing-1. Oncotarget. 2015;6(19):17404.
Liu D, Tao T, Xu B, Chen S, Liu C, Zhang L, et al. MiR-361-5p acts as a tumor suppressor in prostate cancer by targeting signal transducer and activator of transcription-6 (. Biochem Biophys Res Commun. 2014;STAT6(1):151–6. 445(.
Ma F, Zhang L, Ma L, Zhang Y, Zhang J, Guo B. MiR-361-5p inhibits glycolytic metabolism, proliferation and invasion of breast cancer by targeting FGFR1 and MMP-1. J Experimental Clin Cancer Res. 2017;36(1):158.
Rinnerthaler G, Hackl H, Gampenrieder S, Hamacher F, Hufnagl C, Hauser-Kronberger C, et al. miR-16-5p is a stably-expressed housekeeping microRNA in breast cancer tissues from primary tumors and from metastatic sites. Int J Mol Sci. 2016;17(2):156.
Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 2010;251(3):499–505.
Wolff AC, Hammond MEH, 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(1):18–43.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.
Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103–11.
Wu R, Feng J, Yang Y, Dai C, Lu A, Li J, et al. Significance of serum total oxidant/antioxidant status in patients with colorectal cancer. PLoS ONE. 2017;12(1):e0170003.
Rivera MN, Haber DA. Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer. 2005;5(9):699–712.
Loeb DM, Sukumar S. The role of WT1 in oncogenesis: tumor suppressor or oncogene? Int J Hematol. 2002;76(2):117–26.
Hartkamp J, Carpenter B, Roberts SG. The Wilms’ tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi. Mol Cell. 2010;37(2):159–71.
Al-Salam S, Balalaa N, Faour I, Akhter S, Alashari M. HIF-1α, VEGF and WT-1 are protagonists in bilateral primary angiosarcoma of breast: a case report and review of literature. Int J Clin Exp Pathol. 2012;5(3):247.
Hiltunen M, Koistinaho J, Alhonen L, Myà S. Hypermethylation of the WT1 and calcitonin gene promoter regions at chromosome 11p in human colorectal cancer. Br J Cancer. 1997;76(9):1124.
Qi X-W, Zhang F, Yang X-H, Fan L-J, Zhang Y, Liang Y, et al. High Wilms’ tumor 1 mRNA expression correlates with basal-like and ERBB2 molecular subtypes and poor prognosis of breast cancer. Oncol Rep. 2012;28(4):1231–6.
Tahmasebpour N, Feizi MAH, Ziamajidi N, Pouladi N, Montazeri V, Farhadian M, et al. Association of omentin-1 with oxidative stress and clinical significances in patients with breast cancer. Adv Pharm Bull. 2020;10(1):106.
Gönenç A, Özkan Y, Torun M, Şimşek B. Plasma malondialdehyde (MDA) levels in breast and lung cancer patients. J Clin Pharm Ther. 2001;26(2):141–4.
Feng J-F, Lu L, Zeng P, Yang Y-H, Luo J, Yang Y-W, et al. Serum total oxidant/antioxidant status and trace element levels in breast cancer patients. Int J Clin Oncol. 2012;17(6):575–83.
Ching S, Ingram D, Hahnel R, Beilby J, Rossi E. Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study. J Nutr. 2002;132(2):303–6.
Chan M, Liaw CS, Ji SM, Tan HH, Wong CY, Thike AA, et al. Identification of circulating microRNA signatures for breast cancer detection. Clin Cancer Res. 2013;19(16):4477–87.
Cao Z-G, Huang Y-N, Yao L, Liu Y-R, Hu X, Hou Y-F, et al. Positive expression of miR-361-5p indicates better prognosis for breast cancer patients. J Thorac disease. 2016;8(7):1772.
Han J, Yu J, Yu’na Dai JL, Guo M, Song J, Zhou X. Overexpression of miR-361-5p in triple-negative breast cancer (TNBC) inhibits migration and invasion by targeting RQCD1 and inhibiting the EGFR/PI3K/Akt pathway. Bosnian J basic Med Sci. 2019;19(1):52.
Liu B, Wu S, Ma J, Yan S, Xiao Z, Wan L, et al. lncRNA GAS5 reverses EMT and tumor stem cell-mediated gemcitabine resistance and metastasis by targeting miR-221/SOCS3 in pancreatic cancer. Mol Therapy-Nucleic Acids. 2018;13:472–82.
Weng WH, Leung WH, Pang YJ, Kuo LW, Hsu HH. EPA significantly improves anti–EGFR targeted therapy by regulating miR–378 expression in colorectal cancer. Oncol Lett. 2018;16(5):6188–94.
Liu W, Xu Y, Guan H, Meng H. Clinical potential of miR-940 as a diagnostic and prognostic biomarker in breast cancer patients. Cancer Biomarkers. 2018;22(3):487–93.
Mattiske S, Suetani RJ, Neilsen PM, Callen DF. The oncogenic role of miR-155 in breast cancer. Cancer Epidemiol Prev Biomarkers. 2012;21(8):1236–43.
Wang D, Fan Z, Liu F, Zuo J. Hsa-miR-21 and Hsa-miR-29 in tissue as potential diagnostic and prognostic biomarkers for gastric cancer. Cell Physiol Biochem. 2015;37(4):1454–62.
Koutova L, Sterbova M, Pazourkova E, Pospisilova S, Svobodova I, Horinek A, et al. The impact of standard chemotherapy on miRNA signature in plasma in AML patients. Leuk Res. 2015;39(12):1389–95.
Yang S, Zhang Y, Zhao X, Wang J, Shang J. microRNA-361 targets Wilms’ tumor 1 to inhibit the growth, migration and invasion of non-small-cell lung cancer cells. Mol Med Rep. 2016;14(6):5415–21.
Wang K, Qi X, Liu H, Su H. MiR-361 inhibits osteosarcoma cell lines invasion and proliferation by targeting FKBP14. European review for medical and pharmacological sciences. 2018;22:79–86.
Funding
The study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences, Iran (No. 970128396).
Author information
Authors and Affiliations
Contributions
F.P. did all experiments and collected the data, N.Z. generated and developed the study hypothesis and design, R.A. analyzed and interpreted the data, R.N. revised the manuscript, M.F. completed the final version of manuscript. All authors read and confirmed the final manuscript.
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Ethical Approval
The study approved by the Ethics committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1396.919) and was conducted in accordance with the Declaration of Helsinki.
Informed Consent
Informed written consent was obtained from all study participants.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Pishbin, F., Ziamajidi, N., Abbasalipourkabir, R. et al. Correlation of Wilms’ Tumor 1 (WT1) with Oxidative Stress Markers and Expression of miR-361-5p; New Aspect of WT1 in Breast Cancer. Ind J Clin Biochem 38, 338–350 (2023). https://doi.org/10.1007/s12291-022-01053-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12291-022-01053-9