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Isoliquiritigenin Suppresses EMT-Induced Metastasis in Triple-Negative Breast Cancer through miR-200c/C-JUN/β-Catenin

    Triple-negative breast cancer (TNBC) is the subtype of breast cancer with more aggressive growth and metastasis and without efficient therapies. Hence, it is worthwhile to search for potential effective drug candidates. According to our previous study, isoliquiritigenin (ISL) exerted a potent anticancer effect on breast cancer proliferation. Its effect on TNBC growth, metastasis and mechanism deserves further investigation. In this study, PCR array screened a significant increase of miR-200c in BT-549 and MDA-MB-231 cells after ISL treatment, and ISH exerted that miR-200c was expressed at a low level in breast cancer tissue of patients. We also found that ISL could up-regulate miR-200c, resulting in the inhibition of epithelial-mesenchymal transition. Meanwhile, ISL could inhibit metastasis and tumor growth in nude mice models through the increase of miR-200c. Further study displayed that ISL decreased c-Jun expression through the increase of miR-200c. Interestingly, we also detected that ISL might increase miR-200c expression through the demethylation of miR-200c promoter region. These findings indicated that ISL could be potentially developed as a novel drug candidate for TNBC in microRNA-based cancer therapies.

    References

    • Asl, M.N. and H. Hosseinzadeh . Review of pharmacological effects of Glycyrrhiza sp and its bioactive compounds. Phytother. Res. 22: 709–724, 2008. Crossref, Medline, ISIGoogle Scholar
    • Biswas, K.H. , Molecular mobility-mediated regulation of E-cadherin adhesion. Trends Biochem. Sci. 45: 163–173, 2020. Crossref, Medline, ISIGoogle Scholar
    • Chandrashekar, D.S., B. Bashel, S.A.H. Balasubramanya, C.J. Creighton, I. Ponce-Rodriguez, B. Chakravarthi and S. Varambally . UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia 19: 649–658, 2017. Crossref, Medline, ISIGoogle Scholar
    • DeSantis, C., J.M. Ma, L. Bryan and A. Jemal . Breast cancer statistics, 2013. CA Cancer J. Clin. 64: 52–62, 2014. Crossref, Medline, ISIGoogle Scholar
    • Drasin, D.J., T.P. Robin and H.L. Ford . Breast cancer epithelial-to-mesenchymal transition: Examining the functional consequences of plasticity. Breast Cancer Res. 13: 226, 2011. Crossref, Medline, ISIGoogle Scholar
    • Dykxhoorn, D.M., Y.C. Wu, H.M. Xie, F.Y. Yu, A. Lal, F. Petrocca, D. Martinvalet, E. Song, B. Lim and J. Lieberman . miR-200 enhances mouse breast cancer cell colonization to form distant metastases. Plos One 4: e7181, 2009. Crossref, Medline, ISIGoogle Scholar
    • Gao, J., C.M. Cahill, X.D. Huang, J.L. Roffman, S. Lamon-Fava, M. Fava, D. Mischoulon and J.T. Rogers . S-adenosyl methionine and transmethylation pathways in neuropsychiatric diseases throughout life. Neurotherapeutics 15: 156–175, 2018. Crossref, Medline, ISIGoogle Scholar
    • Jiao, X., S. Katiyar, N.E. Willmarth, M. Liu, X. Ma, N. Flomenberg, M.P. Lisanti and R.G. Pestell . c-Jun induces mammary epithelial cellular invasion and breast cancer stem cell expansion. J. Biol. Chem. 285: 8218–8226, 2010. Crossref, Medline, ISIGoogle Scholar
    • Kalluri, R. and R.A. Weinberg . The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119: 1420–1428, 2009. Crossref, Medline, ISIGoogle Scholar
    • Kim, H., S.S. Yi, H.K. Lee, T.H. Heo, S.K. Park, H.S. Jun, K.D. Song and S.J. Kim . Antiproliferative effect of vine stem extract from Spatholobus Suberectus Dunn on rat C6 glioma cells through regulation of ROS, mitochondrial depolarization, and P21 protein expression. Nutr. Cancer 70: 605–619, 2018. Crossref, Medline, ISIGoogle Scholar
    • Lindner, D.J., Y. Wu, R. Haney, B.S. Jacobs, J.P. Fruehauf, R. Tuthill and E.C. Borden . Thrombospondin-1 expression in melanoma is blocked by methylation and targeted reversal by 5-Aza-deoxycytidine suppresses angiogenesis. Matrix Biol. 32: 123–132, 2013. Crossref, Medline, ISIGoogle Scholar
    • Liu, J., Q.K. Han, T.R. Peng, M.X. Peng, B. Wei, D.W. Li, X.S. Wang, S.Y. Yu, J.Q. Yang, S.T. Cao, K.M. Huang, A.P. Hutchins, H. Liu, J.Q. Kuang, Z.W. Zhou, J. Chen, H.Y. Wu, L. Guo, Y.Q. Chen, Y. Chen, X.J. Li, H.L. Wu, HL , B.J. Liao, W. He, H. Song, H.J. Yao, G.J. Pan, J.K. Chen and D.Q. Pei . The oncogene c-Jun impedes somatic cell reprogramming. Nat. Cell. Biol. 17: 856–867, 2015. Crossref, Medline, ISIGoogle Scholar
    • Ljepoja, B., C. Schreiber, F.A. Gegenfurtner, J. Garcia-Roman, B. Kohler, S. Zahler, J.O. Radler, E. Wagner and A. Roidl . Inducible microRNA-200c decreases motility of breast cancer cells and reduces filamin A. Plos One 14: e0224314, 2019. Crossref, Medline, ISIGoogle Scholar
    • Mutlu, M., U. Raza, O. Saatci, E. Eyupoglu, E. Yurdusev and O. Sahin . miR-200c: A versatile watchdog in cancer progression, EMT, and drug resistance. J. Mol. Med. 94: 629–644, 2016. Crossref, Medline, ISIGoogle Scholar
    • Nakagawa, M., Y. Bando, T. Nagao, M. Morimoto, C. Takai, T. Ohnishi, J. Honda, T. Moriya, K. Izumi, M. Takahashi, M. Sasa and A. Tangoku . Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancer. Anticancer Res. 31: 2389–2393, 2011. Medline, ISIGoogle Scholar
    • Park S.M., A.B. Gaur, E. Lengyel and M.E. Peter . The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Gene Dev. 22: 894–907, 2008. Crossref, Medline, ISIGoogle Scholar
    • Peng, F., L. Xiong, X.F. Xie, H. Tang, R.Z. Huang and C. Peng . Isoliquiritigenin derivative regulates miR-374a/BAX axis to suppress triple-negative breast cancer tumorigenesis and development. Front. Pharmacol. 11: 1–12, 2020. Crossref, Medline, ISIGoogle Scholar
    • Peng, F., H. Zhu, C.W. Meng, Y.R. Ren, O. Dai and L. Xiong . New Isoflavanes from Spatholobus suberectus and their cytotoxicity against human breast cancer cell lines. Molecules 24: 1–8, 2019. Crossref, ISIGoogle Scholar
    • Reed, K., M.L. Poulin, L.Y. Yan and A.M. Parissenti . Comparison of bisulfite sequencing PCR with pyrosequencing for measuring differences in DNA methylation. Anal. Biochem. 397: 96–106, 2010. Crossref, Medline, ISIGoogle Scholar
    • Shi, L.L., S. Zhang, H.G. Wu, L.L. Zhang, X.F. Dai, J.L. Hu, J. Xue, T. Liu, Y.C. Liang and G. Wu . MiR-200c Increases the radiosensitivity of non-small-cell lung cancer cell line A549 by targeting VEGF-VEGFR2 pathway. Plos One 8: e78344, 2013. Crossref, Medline, ISIGoogle Scholar
    • Shimono, Y., M. Zabala, R.W. Cho, N. Lobo, P. Dalerba, D. Qian, M. Diehn, H. Liu, S.P. Panula, E. Chiao, F.M. Dirbas, G. Somlo, R.A.R. Pera, K. Q. Lao and M.F. Clarke . Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138: 592–603, 2009. Crossref, Medline, ISIGoogle Scholar
    • Tang, H.L., F. Peng, X.J. Huang, X.H. Xie, B. Chen, J.G. Shen, F. Gao, J.S. You, X.M. Xie and J.P. Chen . Neoisoliquiritigenin inhibits tumor progression by targeting GRP78-beta-catenin signaling in breast cancer. Curr. Cancer Drug Targets 18: 390–399, 2018. Crossref, Medline, ISIGoogle Scholar
    • Trott, O. and A.J. Olson . Software news and update AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31: 455–461, 2010. Medline, ISIGoogle Scholar
    • Tryndyak, V.P., F.A. Beland and I.P. Pogribny . E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int. J. Cancer. 126: 2575–2583, 2010. Medline, ISIGoogle Scholar
    • Vrba, L., T.J. Jensen, J.C. Garbe, R.L. Heimark, A.E. Cress, S. Dickinson, M.R. Stampfer and B.W. Futscher . Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. Plos One 5: e8697, 2010. Crossref, Medline, ISIGoogle Scholar
    • Wang, Y.F., J. Shi, K.Q. Chai, X.H. Ying and B.H.P. Zhou . The role of snail in EMT and tumorigenesis. Curr. Cancer Drug Targets 13: 963–972, 2013b. Crossref, Medline, ISIGoogle Scholar
    • Wang, Z.Y., N. Wang, P.X. Liu, Q.J. Chen, H.L. Situ, T. Xie, J.X. Zhang, C. Peng, Y. Lin and J.P. Chen . MicroRNA-25 regulates chemoresistance-associated autophagy in breast cancer cells, a process modulated by the natural autophagy inducer isoliquiritigenin. Oncotarget 5: 7013–7026, 2014. Crossref, MedlineGoogle Scholar
    • Wang, Z.Y., D.M. Wang, S.W. Han, N. Wang, F.Z. Mo, T.Y. Loo, J.G. Shen, H. Huang and J.P. Chen . Bioactivity-guided identification and cell signaling technology to delineate the lactate dehydrogenase A inhibition effects of Spatholobus suberectus on breast cancer. PloS One 8: e56631, 2013b. Crossref, Medline, ISIGoogle Scholar
    • Yang, L., H.L. Tang, Y.N. Kong, X.F. Xie, J.P. Chen, C.L. Song, X.P. Liu, F. Ye, N. Li, N. Wang and X.M. Xie . LGR5 promotes breast cancer progression and maintains stem-like cells through activation of Wnt/beta-Catenin signaling. Stem Cells 33: 2913–2924, 2015. Crossref, Medline, ISIGoogle Scholar
    • Yen, R.W., P.M. Vertino, B.D. Nelkin, J.J. Yu, W. el-Deiry, A. Cumaraswamy, G.G. Lennon, B.J. Trask, P. Celano and S.B. Baylin . Isolation and characterization of the cDNA encoding human DNA methyltransferase. Nucleic Acids Res. 20: 2287–2291, 1992. Crossref, Medline, ISIGoogle Scholar
    • Zhang, X., X. Li, J.L. Li, Q.W. Wang, W.L. Zou, Y.Q. Liu, Z.Q. Jia, F. Peng and B. Han . Regiodivergent construction of medium-sized heterocycles from vinylethylene carbonates and allylidenemalononitriles. Chem. Sci. 11: 2888–2894, 2020. Crossref, Medline, ISIGoogle Scholar
    Published: 25 February 2021
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