Isoliquiritigenin Suppresses EMT-Induced Metastasis in Triple-Negative Breast Cancer through miR-200c/C-JUN/-Catenin
Abstract
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
- . Review of pharmacological effects of Glycyrrhiza sp and its bioactive compounds. Phytother. Res. 22: 709–724, 2008. Crossref, Medline, ISI, Google Scholar
- , Molecular mobility-mediated regulation of E-cadherin adhesion. Trends Biochem. Sci. 45: 163–173, 2020. Crossref, Medline, ISI, Google Scholar
- . UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia 19: 649–658, 2017. Crossref, Medline, ISI, Google Scholar
- . Breast cancer statistics, 2013. CA Cancer J. Clin. 64: 52–62, 2014. Crossref, Medline, ISI, Google Scholar
- . Breast cancer epithelial-to-mesenchymal transition: Examining the functional consequences of plasticity. Breast Cancer Res. 13: 226, 2011. Crossref, Medline, ISI, Google Scholar
- . miR-200 enhances mouse breast cancer cell colonization to form distant metastases. Plos One 4: e7181, 2009. Crossref, Medline, ISI, Google Scholar
- . S-adenosyl methionine and transmethylation pathways in neuropsychiatric diseases throughout life. Neurotherapeutics 15: 156–175, 2018. Crossref, Medline, ISI, Google Scholar
- . c-Jun induces mammary epithelial cellular invasion and breast cancer stem cell expansion. J. Biol. Chem. 285: 8218–8226, 2010. Crossref, Medline, ISI, Google Scholar
- . The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119: 1420–1428, 2009. Crossref, Medline, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . The oncogene c-Jun impedes somatic cell reprogramming. Nat. Cell. Biol. 17: 856–867, 2015. Crossref, Medline, ISI, Google Scholar
- . Inducible microRNA-200c decreases motility of breast cancer cells and reduces filamin A. Plos One 14: e0224314, 2019. Crossref, Medline, ISI, Google Scholar
- . miR-200c: A versatile watchdog in cancer progression, EMT, and drug resistance. J. Mol. Med. 94: 629–644, 2016. Crossref, Medline, ISI, Google Scholar
- . Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancer. Anticancer Res. 31: 2389–2393, 2011. Medline, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . Isoliquiritigenin derivative regulates miR-374a/BAX axis to suppress triple-negative breast cancer tumorigenesis and development. Front. Pharmacol. 11: 1–12, 2020. Crossref, Medline, ISI, Google Scholar
- . New Isoflavanes from Spatholobus suberectus and their cytotoxicity against human breast cancer cell lines. Molecules 24: 1–8, 2019. Crossref, ISI, Google Scholar
- . Comparison of bisulfite sequencing PCR with pyrosequencing for measuring differences in DNA methylation. Anal. Biochem. 397: 96–106, 2010. Crossref, Medline, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138: 592–603, 2009. Crossref, Medline, ISI, Google Scholar
- . Neoisoliquiritigenin inhibits tumor progression by targeting GRP78-beta-catenin signaling in breast cancer. Curr. Cancer Drug Targets 18: 390–399, 2018. Crossref, Medline, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . The role of snail in EMT and tumorigenesis. Curr. Cancer Drug Targets 13: 963–972, 2013b. Crossref, Medline, ISI, Google Scholar
- . 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, Medline, Google Scholar
- . 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, ISI, Google Scholar
- . 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, ISI, Google Scholar
- . Isolation and characterization of the cDNA encoding human DNA methyltransferase. Nucleic Acids Res. 20: 2287–2291, 1992. Crossref, Medline, ISI, Google Scholar
- . Regiodivergent construction of medium-sized heterocycles from vinylethylene carbonates and allylidenemalononitriles. Chem. Sci. 11: 2888–2894, 2020. Crossref, Medline, ISI, Google Scholar
| Remember to check out the Most Cited Articles! |
|---|
|
Check out our Chinese Medicine Titles today. |


