miRNA-155 as a Novel Target for Isoliquiritigenin to Induce Autophagy in Oral Squamous Cell Carcinoma
DOI:
https://doi.org/10.3889/oamjms.2022.8278Keywords:
Isoliquiritigenin, miRNA-155, miRNA-21, Autophagy and oral squamous cell carcinomaAbstract
Background and Aim :The most common obstacle facing chemotherapeutic agents is the development of drug resistance to cancer cells by dysregulation of autophagy and apoptosis. Targeting miRNAs by a natural flavonoid such as Isoliquiritigenin (ISL) is a novel strategy to reverse drug resistance. The aim of the present study was to evaluate ISL impacts on apoptosis and autophagy in oral squamous carcinoma cells (OSCC) through the expression levels of related two microRNAs: miRNA-21 and miRNA-155. Materials & Methods: The expression levels of both miRNAs were analysed using quantitative real time PCR and the effect of ISL on apoptosis was evaluated using annexin assay. In addition, the expression of the autophagy marker (ATG7) was measured using immunofluorescence. Results : Our results showed that ISL significantly downregulated both miRNA-21 and miRNA-155 with a fold change of 22.01 and 52.35, respectively. It also induced apoptosis in the cancer cells with high percentage (51.3 %). Moreover, ATG7 was highly expressed after ISL treatment. Conclusion : From this sudy we can conclude that ISL has an apoptotic and autophagic effect on OSCC through the down-regulation of miRNA-21 and miRNA-155, major regulators of PI3K/Akt pathway which can provide novel targets for OSCC therapy.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Rivera C, Venegas B. Histological and molecular aspects of oral squamous cell carcinoma. Oncol Lett. 2014;8:7-11. https://doi.org/10.3892/ol.2014.2103 PMid:24959211 DOI: https://doi.org/10.3892/ol.2014.2103
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660 PMid:33538338 DOI: https://doi.org/10.3322/caac.21660
Bello IO, Soini Y, Salo T. Prognostic evaluation of oral tongue cancer: Means, markers and perspectives (I). Oral Oncol. 2010;46(9):636-43. https://doi.org/10.1016/j.oraloncology PMid:20637679 DOI: https://doi.org/10.1016/j.oraloncology.2010.06.008
Ghantous Y, Abu Elnaaj I. Global incidence and risk factors of oral cancer. Harefuah. 2017;156(10):645-9.
Ghani WM, Razak IA, Doss JG, Yang YH, Rahman ZAA, Ismail SM, et al. Multi-ethnic variations in the practice of oral cancer risk habits in a developing country. Oral Dis. 2019;25(2):447-55. https://doi.org/10.1111/odi.12995 PMid:30350902 DOI: https://doi.org/10.1111/odi.12995
Mroueh R, Haapaniemi A, Grénman R, Laranne J, Pukkila M, Almangush A, et al. Improved outcomes with oral tongue squamous cell carcinoma in Finland. Head Neck. 2017;39(7):1306-12. https://doi.org/10.1002/hed.24744 PMid:28481417 DOI: https://doi.org/10.1002/hed.24744
Shan C, Chen X, Cai H, et al. The emerging roles of autophagy-related micrornas in cancer. Int J Biol Sci. 2021;17(1):134-50. https://doi.org/10.7150/ijbs.50773 PMid:33390839 DOI: https://doi.org/10.7150/ijbs.50773
Falzone L, Lupo G, La Rosa GR, Crimi S, Anfuso CD, Salemi R, et al. Identification of novel microRNAs and their diagnostic and prognostic significance in oral cancer. Cancers (Basel). 2019;11(5):610. https://doi.org/10.3390/cancers11050610 PMid:31052345 DOI: https://doi.org/10.3390/cancers11050610
Liu C, Tong Z, Tan J, Xin Z, Wang Z, Tian L. MicroRNA215p targeting PDCD4 suppresses apoptosis via regulating the PI3K/AKT/FOXO1 signaling pathway in tongue squamous cell carcinoma. Exp Ther Med. 2019;18(5):3543-51. https://doi.org/10.3892/etm.2019.7970 PMid:31602231 DOI: https://doi.org/10.3892/etm.2019.7970
Wang Z, Wang N, Liu P, Chen Q, Situ H, Xie T, et al. MicroRNA-25 regulates chemoresistance-associated autophagy in breast cancer cells, a process modulated by the natural autophagy inducer isoliquiritigenin. Oncotarget. 2014;5(16):7013. https://doi.org/10.18632/oncotarget.2192 PMid:25026296 DOI: https://doi.org/10.18632/oncotarget.2192
Santos JC, Lima NDS, Sarian LO, Matheu A, Ribeiro ML, Derchain SF. Exosome-mediated breast cancer chemoresistance via miR-155 transfer. Sci Rep. 2018;8(1):1-11. https://doi.org/10.1038/s41598-018-19339-5 PMid:29339789 DOI: https://doi.org/10.1038/s41598-018-19339-5
Wan G, Xie W, Liu Z, Xu W, Lao Y, Huang N, et al. Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway. Autophagy. 2014;10(1):70-9. https://doi.org/10.4161/auto.26534 PMid:24262949 DOI: https://doi.org/10.4161/auto.26534
Peng F, Du Q, Peng C, Wang N, Tang H, Xie X, et al. A review: The pharmacology of isoliquiritigenin. Phyther Res. 2015;29(7):969-77. https://doi.org/10.1002/ptr.5348 PMid:25907962 DOI: https://doi.org/10.1002/ptr.5348
Hou C, Li W, Li Z, Gao J, Chen Z, Zhao X, et al. Synthetic isoliquiritigenin inhibits human tongue squamous carcinoma cells through its antioxidant mechanism. Oxid Med Cell Longev. 2017;2017:1379430. https://doi.org/10.1155/2017/1379430 PMid:28203317 DOI: https://doi.org/10.1155/2017/1379430
Hsia SM, Yu CC, Shih YH, Chen MY, Wang TH, Huang YT, et al. Isoliquiritigenin as a cause of DNA damage and inhibitor of ataxia-telangiectasia mutated expression leading to G2/M phase arrest and apoptosis in oral squamous cell carcinoma. Head Neck. 2015;38 Suppl 1:E360-71. https://doi.org/10.1002/hed.24001 PMid:25580586 DOI: https://doi.org/10.1002/hed.24001
Aung TN, Qu Z, Kortschak RD, Adelson DL. Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int J Mol Sci. 2017;18(3):656. https://doi.org/10.3390/ijms18030656 PMid:28304343 DOI: https://doi.org/10.3390/ijms18030656
Manson MM. Cancer prevention-the potential for diet to modulate molecular signalling. Trends Mol Med. 2003;9(1):11-8. https://doi.org/10.1016/s1471-4914(02)00002-3 PMid:12524205 DOI: https://doi.org/10.1016/S1471-4914(02)00002-3
Prakash O, Kumar A, Kumar P, Ajeet. Anticancer potential of plants and natural products: A review. Am J Pharmacol Sci. 2013;1(6):104-15. https://doi.org/10.12691/ajps-1-6-1 DOI: https://doi.org/10.12691/ajps-1-6-1
Wang KL, Yu YC, Hsia SM. Perspectives on the role of isoliquiritigenin in cancer. Cancers (Basel). 2021;13(1):115. https://doi.org/10.3390/cancers13010115 PMid:33401375 DOI: https://doi.org/10.3390/cancers13010115
Ii T, Satomi Y, Katoh D, Shimada J, Baba M, Okuyama T, et al. Induction of cell cycle arrest and p21(CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin. Cancer Lett. 2004;207(1):27-35. https://doi.org/10.1016/j.canlet.2003.10.023 PMid:15050731 DOI: https://doi.org/10.1016/j.canlet.2003.10.023
Wang KL, Hsia SM, Chan CJ, Chang FY, Huang CY, Bau DT, et al. Inhibitory effects of isoliquiritigenin on the migration and invasion of human breast cancer cells. Expert Opin Ther Targets. 2013;17(4):337-49. https://doi.org/10.1517/14728222.2013.756869 PMid:23327692 DOI: https://doi.org/10.1517/14728222.2013.756869
Tian T, Sun J, Wang J, Liu Y, Liu H. Isoliquiritigenin inhibits cell proliferation and migration through the PI3K/AKT signaling pathway in A549 lung cancer cells. Oncol Lett. 2018;16(5):6133-9. https://doi.org/10.3892/ol.2018.9344 PMid:30344755 DOI: https://doi.org/10.3892/ol.2018.9344
Safdari Y, Khalili M, Ebrahimzadeh MA, Yazdani Y, Farajnia S. Natural inhibitors of PI3K/AKT signaling in breast cancer: Emphasis on newly-discovered molecular mechanisms of action. Pharmacol Res. 2015;93:1-10. https://doi.org/10.1016/j.phrs.2014.12.004 PMid:25533812 DOI: https://doi.org/10.1016/j.phrs.2014.12.004
Jin H, Seo GS, Lee SH. Isoliquiritigenin-mediated p62/SQSTM1 induction regulates apoptotic potential through attenuation of caspase-8 activation in colorectal cancer cells. Eur J Pharmacol. 2018;841:90-7. https://doi.org/10.1016/j.ejphar.2018.10.015 PMid:30339814 DOI: https://doi.org/10.1016/j.ejphar.2018.10.015
Jung SK, Lee MH, Lim DY, Kim JE, Singh P, Lee SY, et al. Isoliquiritigenin induces apoptosis and inhibits xenograft tumor growth of human lung cancer cells by targeting both wild type and L858R/T790M mutant EGFR. J Biol Chem. 2014;289(52):35839-48. https://doi.org/10.1074/jbc.M114.585513 PMid:25368326 DOI: https://doi.org/10.1074/jbc.M114.585513
Zhang B, Lai Y, Li Y, Shu N, Wang Z, Wang Y, et al. Antineoplastic activity of isoliquiritigenin, a chalcone compound, in androgen-independent human prostate cancer cells linked to G2/M cell cycle arrest and cell apoptosis. Eur J Pharmacol. 2018;821:57-67. https://doi.org/10.1016/j.ejphar.2017.12.053 PMid:29277717 DOI: https://doi.org/10.1016/j.ejphar.2017.12.053
Si LL, Yang XH, Yan XY, Wang YM, Zheng Q. Isoliquiritigenin induces apoptosis of human bladder cancer T24 cells via a cyclin-dependent kinase-independent mechanism. Oncol Lett. 2017;14(1):241-9. https://doi.org/10.3892/ol.2017.6159 PMid:28693160 DOI: https://doi.org/10.3892/ol.2017.6159
Xiang S, Chen H, Luo X, An B, Wu W, Cao S, et al. Isoliquiritigenin suppresses human melanoma growth by targeting miR-301b/LRIG1 signaling. J Exp Clin Cancer Res. 2018;37(1):184. https://doi.org/10.1186/s13046-018-0844-x PMid:30081934 DOI: https://doi.org/10.1186/s13046-018-0844-x
Sun C, Wang ZH, Liu XX, Yang LN, Wang Y, Liu Y, et al. Disturbance of redox status enhances radiosensitivity of hepatocellular carcinoma. Am J Cancer Res. 2015;5(4):1368. https://doi.org/10.1016/s0959-8049(17)30342-8 PMid:26101703 DOI: https://doi.org/10.1016/S0959-8049(17)30342-8
Wu CH, Chen HY, Wang CW, Shieh TM, Huang TC, Lin LC, et al. Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice. Oncotarget. 2016;7(45):73432-47. https://doi.org/10.18632/oncotarget.12369 PMid:27708238 DOI: https://doi.org/10.18632/oncotarget.12369
Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296(5573):1655-7. https://doi.org/10.1126/science.296.5573.1655 PMid:12040186 DOI: https://doi.org/10.1126/science.296.5573.1655
Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605-35. https://doi.org/10.1016/j.cell.2017.07.029 PMid:28802037 DOI: https://doi.org/10.1016/j.cell.2017.07.029
Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005;4(12):988-1004. https://doi.org/10.1038/nrd1902 PMid:16341064 DOI: https://doi.org/10.1038/nrd1902
Downloads
Published
How to Cite
License
Copyright (c) 2022 Loay Abdellatef Mohamed, Amr Helmy Mostafa El Bolok, Sherif Farouk Elgayar, Ahmed Nabel Fahmy (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0