Aflatoxin B1 Negatively Regulates Wnt/β-catenin Signaling Pathway Through Activating MiR-33a

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Sep 10

PMID 24015284

Citations 32

Authors

Yi Fang

Youjun Feng

Tongjin Wu

Swaminath Srinivas

Weiqiang Yang

Jue Fan

Chi Yang

Shihua Wang

Affiliations

Soon will be listed here.

Abstract

MicroRNAs are known to play an important role in modulating gene expression in various diseases including cancers and cardiovascular disorders, but only a few of them are associated with the pathology of aflatoxin B1 (AFB1), a potent mycotoxin. Here, we discovered a novel regulatory network between AFB1, miR-33a and β-catenin in human carcinoma cells. The level of miR-33a was up-regulated in hepatocellular carcinoma (HCC) cells treated with AFB1, while in the same cells causing the decrease in β-catenin expression when treated at their IC50 values. miR-33a, specifically miR-33a-5p, was demonstrated to down-regulate the expression of β-catenin, affect the β-catenin pathway, and inhibit cell growth. Also, by employing a luciferase assay, we found that miR-33a down-regulated β-catenin by directly binding to the 3'-UTR of β-catenin. These results suggested that AFB1 might down-regulate β-catenin by up-regulating miR-33a. This understanding opens new lines of thought in the potential role of miR-33a in the clinical therapy of cancer.

Citing Articles

The Detoxification Effects of Melatonin on Aflatoxin-Caused Toxic Effects and Underlying Molecular Mechanisms.

Dai C, Li D, Velkov T, Shen J, Hao Z Antioxidants (Basel). 2025; 13(12.

PMID: 39765856 PMC: 11726890. DOI: 10.3390/antiox13121528.

MicroRNAs: exploring their role in farm animal disease and mycotoxin challenges.

Kappari L, Dasireddy J, Applegate T, Selvaraj R, Shanmugasundaram R Front Vet Sci. 2024; 11:1372961.

PMID: 38803799 PMC: 11129562. DOI: 10.3389/fvets.2024.1372961.

Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions.

Li M, Tang S, Peng X, Sharma G, Yin S, Hao Z Antioxidants (Basel). 2024; 13(4).

PMID: 38671900 PMC: 11047733. DOI: 10.3390/antiox13040452.

The role of inflammatory and remodelling biomarkers in patients with non-small cell lung cancer.

Omer H, Janson C, Amin K Cent Eur J Immunol. 2024; 48(4):330-337.

PMID: 38558564 PMC: 10976650. DOI: 10.5114/ceji.2023.133725.

Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers.

Catalano T, Selvaggi F, Esposito D, Cotellese R, Aceto G Microorganisms. 2023; 11(7).

PMID: 37512809 PMC: 10386003. DOI: 10.3390/microorganisms11071632.

References

Hu W, Coller J . What comes first: translational repression or mRNA degradation? The deepening mystery of microRNA function. Cell Res. 2012; 22(9):1322-4. PMC: 3434348. DOI: 10.1038/cr.2012.80. View

Bernstein E, Caudy A, Hammond S, Hannon G . Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001; 409(6818):363-6. DOI: 10.1038/35053110. View

Brennecke J, Hipfner D, Stark A, Russell R, Cohen S . bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003; 113(1):25-36. DOI: 10.1016/s0092-8674(03)00231-9. View

Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y . CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010; 38(16):5366-83. PMC: 2938198. DOI: 10.1093/nar/gkq285. View

Pineau P, Marchio A, Battiston C, Cordina E, Russo A, Terris B . Chromosome instability in human hepatocellular carcinoma depends on p53 status and aflatoxin exposure. Mutat Res. 2008; 653(1-2):6-13. DOI: 10.1016/j.mrgentox.2008.01.012. View

Xia H, Cheung W, Sze J, Lu G, Jiang S, Yao H . miR-200a regulates epithelial-mesenchymal to stem-like transition via ZEB2 and beta-catenin signaling. J Biol Chem. 2010; 285(47):36995-7004. PMC: 2978628. DOI: 10.1074/jbc.M110.133744. View

Devereux T, Stern M, Flake G, Yu M, Zhang Z, London S . CTNNB1 mutations and beta-catenin protein accumulation in human hepatocellular carcinomas associated with high exposure to aflatoxin B1. Mol Carcinog. 2001; 31(2):68-73. DOI: 10.1002/mc.1041. View

Kumar M, Zhao X, Wang X . Molecular carcinogenesis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: one step closer to personalized medicine?. Cell Biosci. 2011; 1(1):5. PMC: 3116244. DOI: 10.1186/2045-3701-1-5. View

Yunus A, Razzazi-Fazeli E, Bohm J . Aflatoxin B(1) in affecting broiler's performance, immunity, and gastrointestinal tract: a review of history and contemporary issues. Toxins (Basel). 2011; 3(6):566-90. PMC: 3202846. DOI: 10.3390/toxins3060566. View

10.

Magrelli A, Azzalin G, Salvatore M, Viganotti M, Tosto F, Colombo T . Altered microRNA Expression Patterns in Hepatoblastoma Patients. Transl Oncol. 2009; 2(3):157-63. PMC: 2730135. DOI: 10.1593/tlo.09124. View

11.

Liang L, Wong C, Ying Q, Fan D, Huang S, Ding J . MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2. Hepatology. 2010; 52(5):1731-40. DOI: 10.1002/hep.23904. View

12.

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

13.

Coller J, Parker R . General translational repression by activators of mRNA decapping. Cell. 2005; 122(6):875-86. PMC: 1853273. DOI: 10.1016/j.cell.2005.07.012. View

14.

Eaton D, Gallagher E . Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol. 1994; 34:135-72. DOI: 10.1146/annurev.pa.34.040194.001031. View

15.

Ventura A, Jacks T . MicroRNAs and cancer: short RNAs go a long way. Cell. 2009; 136(4):586-91. PMC: 3910108. DOI: 10.1016/j.cell.2009.02.005. View

16.

Bianco G, Russo R, Marzocco S, Velotto S, Autore G, Severino L . Modulation of macrophage activity by aflatoxins B1 and B2 and their metabolites aflatoxins M1 and M2. Toxicon. 2012; 59(6):644-50. DOI: 10.1016/j.toxicon.2012.02.010. View

17.

Strosnider H, Azziz-Baumgartner E, Banziger M, Bhat R, Breiman R, Brune M . Workgroup report: public health strategies for reducing aflatoxin exposure in developing countries. Environ Health Perspect. 2006; 114(12):1898-903. PMC: 1764136. DOI: 10.1289/ehp.9302. View

18.

Raney V, Harris T, Stone M . DNA conformation mediates aflatoxin B1-DNA binding and the formation of guanine N7 adducts by aflatoxin B1 8,9-exo-epoxide. Chem Res Toxicol. 1993; 6(1):64-8. DOI: 10.1021/tx00031a010. View

19.

McGlynn K, London W . Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol. 2005; 19(1):3-23. DOI: 10.1016/j.bpg.2004.10.004. View

20.

Peterson S, Lampe J, Bammler T, Gross-Steinmeyer K, Eaton D . Apiaceous vegetable constituents inhibit human cytochrome P-450 1A2 (hCYP1A2) activity and hCYP1A2-mediated mutagenicity of aflatoxin B1. Food Chem Toxicol. 2006; 44(9):1474-84. DOI: 10.1016/j.fct.2006.04.010. View