EXPRESSION PATTERN OF miR-125b-2, -155, -221, AND -320a IS ASSOCIATED WITH RESPONSE OF BREAST CANCER PATIENTS TO TAMOXIFEN
Keywords:breast cancer, miRNA, resistance, tamoxifen
Background: Hormonal therapy is one of the main methods of comprehensive treatment of patients with locally advanced breast cancer (BC). Despite the intensive search for molecules associated with the aggressiveness of the tumor process, currently there are no reliable markers predicting response to neoadjuvant hormonal therapy (NHT). Aim: To investigate the correlation between miR-125b-2, -155, -221, -320a expression in tumor tissue and HER2/neu status and response to tamoxifen treatment in BC patients. Materials and Methods: Expression levels of miR-125b-2, -155, -221, and -320a were analyzed in biopsy samples of 50 BC patients using a real-time polymerase chain reaction. Results: We found that levels of miR-125b-2, -155, -221, and -320a were 1.72, 1.65, 1.85, and 2.89 times higher in BC biopsy samples expressing estrogen/progesterone receptors and HER2/neu compared with HER2/neu-negative luminal tumors. Patients with a luminal BC showing higher levels of miR-125b-2 and miR-320a expression before therapy demonstrated better response to NHT with tamoxifen. A strong correlation was calculated for miR-221 expression and response to NHT (r = 0.61). Conclusions: The high levels of miR-125b-2, -155, -221, and -320a in tumor tissue are associated with the HER2/neu-positive status of luminal BC subtypes. Tumor samples of patients showing the low response to NHT with tamoxifen are characterized by lower expression of miR-125b-2 and -320a. Hence, miR-125b-2 and -320a could be considered as putative predictive biomarkers associated with tamoxifen sensitivity of hormone-dependent BC.
Ye P, Fang C, Zeng H, et al. Differential microRNA expression profiles in tamoxifen-resistant human breast cancer cell lines induced by two methods. Oncol Lett 2018; 15: 3532–9. doi: https://doi.org/10.13892/ol.2018.7768
Chekhun VF, Borikun TV, Bazas VM, et al. Association of circulating miR-21, -205, and -182 with response of luminal breast cancers to neoadjuvant FAC and AC treatment. Exp Oncol 2020; 42: 162–6. doi: https://doi.org/10.132471/exp-oncology.2312-8852.vol-42-no-3.14805
Miller TE, Ghoshal K, Ramaswamy B, et al. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem 2008; 283: 29897–903. doi: https://doi.org/10.11074/jbc.M804612200
Shah MY, Calin GA. MicroRNAs miR-221 and miR-222: a new level of regulation in aggressive breast cancer. Genome Med 2011; 3: 1–4. doi: https://doi.org/10.11186/gm272
Di Leva G, Gasparini P, Piovan C, et al. MicroRNA cluster 221-222 and estrogen receptor alpha interactions in breast cancer. J Natl Cancer Inst 2010; 102: 706–21. doi: https://doi.org/10.11093/jnci/djq102
Amiruddin A, Massi M, Islam A, et al. microRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study. Ann Med Surg (Lond) 2021; 73: 103092. doi: https://doi.org/10.11016/j.amsu.2021.103092
Mukherjee P, Sharma S, Sheikh ZA, et al. Correlation of clinico-pathologic and radiologic parameters of response to neoadjuvant chemotherapy in breast cancer. Indian J Cancer 2014; 51: 25–9. doi: https://doi.org/10.14103/0019-509X.134610
Ye J, Xu M, Tian X, Cai S, Zeng S. Research advances in the detection of miRNA. J Pharm Anal 2019; 9: 217–26. doi: https://doi.org/10.11016/j.jpha.2019.05.004
Sui M, Jiao A, Zhai H, et al. Upregulation of miR-125b is associated with poor prognosis and trastuzumab resistance in HER2-positive gastric cancer. Exp Ther Med 2017; 14: 657–63. doi: https://doi.org/10.13892/etm.2017.4548
Luo Y, Wang X, Niu W, et al. Elevated microRNA-125b levels predict a worse prognosis in HER2-positive breast cancer patients. Oncol Lett 2017; 13: 867–74. doi: https://doi.org/10.13892/ol.2016.5482
Lu Z, Ye Y, Jiao D, et al. miR-155 and miR-31 are differentially expressed in breast cancer patients and are correlated with the estrogen receptor and progesterone receptor status. Oncol Lett 2012; 4: 1027–32. doi: https://doi.org/10.13892/ol.2012.841
Song CG, Wu XY, Fu FM, et al. Correlation of miR-155 on formalin-fixed paraffin embedded tissues with invasiveness and prognosis of breast cancer. Zhonghua Wai Ke Za Zhi 2012; 50: 1011–4.
Shao X, Zheng Y, Huang Y, et al. Hsa-miR-221-3p promotes proliferation and migration in HER2-positive breast cancer cells by targeting LASS2 and MBD2. Histol Histopathol 2022; 37: 1099–112. doi: https://doi.org/10.114670/HH-18-483
Gorbatenko A, Søkilde R, Sorensen EE, et al. HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503. Sci Rep 2019; 9: 1–16. doi: https://doi.org/10.11038/s41598-019-39733-x
Liu S, Wang Z, Liu Z, et al. miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer. J Mol Cell Biol 2018; 10: 302–15. doi: https://doi.org/10.11093/jmcb/mjy041
Yang H, Yu J, Wang L, et al. miR-320a is an independent prognostic biomarker for invasive breast cancer. Oncol Lett 2014; 8: 1043–50. doi: https://doi.org/10.13892/ol.2014.2298
Lukianova NY, Borikun TV, Chekhun VF. Tumor microenvironment-derived miRNAs as prognostic markers of breast cancer. Exp Oncol 2019; 41: 242–7. doi: https://doi.org/10.132471/exp-oncology.2312-8852.vol-41-no-3.13615
Matuszyk J, Klopotowska D. miR-125b lowers sensitivity to apoptosis following mitotic arrest: Implications for breast cancer therapy. J Cell Physiol 2020; 235: 6335–44. doi: https://doi.org/10.11002/jcp.29610
Zedain A, Badrway H, Refaat A, et al. Using miR-125b in the prediction of aromatase inhibitors resistance in metastatic breast cancer. J Cancer Tumor International 2020; 1: 1–9. doi: https://doi.org/10.19734/jcti/2020/v10i330127
Kim C, Go EJ, Kim A. Recurrence prediction using microRNA expression in hormone receptor positive breast cancer during tamoxifen treatment. Biomarkers 2018; 23: 804–11. doi: https://doi.org/10.11080/1354750X.2018.1499131
Shen R, Wang Y, Wang CX, et al. MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. Am J Transl Res 2015; 7: 2115–26.
Ouyang YX, Feng J, Wang Z, et al. miR-221/222 sponge abrogates tamoxifen resistance in ER-positive breast cancer cells through restoring the expression of ERα. Mol Biomed 2021; 2: 20. doi: https://doi.org/10.11186/s43556-021-00045-0
Gan R, Yang Y, Yang X, et al. Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3. Cancer Gene Ther 2014; 21: 290–6. doi: https://doi.org/10.11038/cgt.2014.29
Iida M, Hazama S, Tsunedomi R, et al. Overexpression of miR 221 and miR 222 in the cancer stroma is associated with malignant potential in colorectal cancer. Oncol Rep 2018; 40: 1621–31. doi: https://doi.org/10.13892/or.2018.6575
Ravegnini G, Cargnin S, Sammarini G, et al. Prognostic role of miR-221 and miR-222 expression in cancer patients: A systematic review and meta-analysis. Cancers (Basel) 2019; 11: 970. doi: https://doi.org/10.13390/cancers11070970
Lü M, Ding K, Zhang G, et al. MicroRNA-320a sensitizes tamoxifen-resistant breast cancer cells to tamoxifen by targeting ARPP-19 and ERRγ. Sci Rep 2015; 5: 8735. doi: https://doi.org/10.11038/srep08735
How to Cite
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.