Skip to main content Accessibility help

Up-regulation of miR-24-1-5p is involved in the chemoprevention of colorectal cancer by black raspberry anthocyanins

  • He Zhang (a1), Jun Guo (a1), Liping Mao (a1), Qianqian Li (a1), Mengnan Guo (a1), Teng Mu (a1), Qiuhua Zhang (a2) and Xiuli Bi (a1) (a3)...


As important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed β-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target β-catenin and trigger a negative regulatory loop for β-catenin and its downstream target genes. β-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of β-catenin, and this may provide a novel chemopreventive and therapeutic strategy for β-catenin signalling-driven colorectal cancer.


Corresponding author

*Corresponding author: X. Bi, email,


Hide All

These authors contributed equally to this work.



Hide All
1. Jemal, A, Bray, F, Center, MM, et al. (2011) Global cancer statistics. CA Cancer J Clin 61, 6990.
2. Jemal, A, Siegel, R, Xu, J, et al. (2010) Cancer statistics, 2010. CA Cancer J Clin 60, 277300.
3. Lin, CC, Gray, PJ, Jemal, A, et al. (2015) Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer. J Natl Cancer Inst 107, djv119.
4. Schoen, RE, Pinsky, PF, Weissfeld, JL, et al. (2012) Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 366, 23452357.
5. Zauber, AG, Winawer, SJ, O’Brien, MJ, et al. (2012) Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 366, 687696.
6. Pessaux, P, Chenard, MP, Bachellier, P, et al. (2010) Consequences of chemotherapy on resection of colorectal liver metastases. J Visc Surg 147, e193e201.
7. Srivastava, K & Srivastava, A (2012) Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk. PLOS ONE 7, e50966.
8. Tokarz, P & Blasiak, J (2012) The role of microRNA in metastatic colorectal cancer and its significance in cancer prognosis and treatment. Acta Biochim Pol 59, 467474.
9. Bhardwaj, A, Singh, S & Singh, AP (2010) MicroRNA-based cancer therapeutics: big hope from small RNAs. Mol Cell Pharmacol 2, 213219.
10. Bartel, DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281297.
11. Cho, WC (2010) MicroRNAs in cancer – from research to therapy. Biochim Biophys Acta 1805, 209217.
12. Michael, MZ, O’Connor, SM, van Holst Pellekaan, NG, et al. (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1, 882891.
13. Monzo, M, Navarro, A, Bandres, E, et al. (2008) Overlapping expression of microRNAs in human embryonic colon and colorectal cancer. Cell Res 18, 823833.
14. Tazawa, H, Tsuchiya, N, Izumiya, M, et al. (2007) Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A 104, 1547215477.
15. Bandres, E, Bitarte, N, Arias, F, et al. (2009) microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res 15, 22812290.
16. Guo, H, Hu, X, Ge, S, et al. (2012) Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell proliferation. Int J Biochem Cell Biol 44, 14651472.
17. Sun, JY, Huang, Y, Li, JP, et al. (2012) MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting beta-catenin. Biochem Biophys Res Commun 420, 787792.
18. Lagos-Quintana, M, Rauhut, R, Lendeckel, W, et al. (2001) Identification of novel genes coding for small expressed RNAs. Science 294, 853858.
19. Sun, Q, Zhang, Y, Yang, G, et al. (2008) Transforming growth factor-beta-regulated miR-24 promotes skeletal muscle differentiation. Nucleic Acids Res 36, 26902699.
20. Guo, Y, Fu, W, Chen, H, et al. (2012) miR-24 functions as a tumor suppressor in Hep2 laryngeal carcinoma cells partly through down-regulation of the S100A8 protein. Oncol Rep 27, 10971103.
21. Mishra, PJ, Song, B, Mishra, PJ, et al. (2009) MiR-24 tumor suppressor activity is regulated independent of p53 and through a target site polymorphism. PLoS ONE 4, e8445.
22. Szczyrba, J, Nolte, E, Hart, M, et al. (2013) Identification of ZNF217, hnRNP-K, VEGF-A and IPO7 as targets for microRNAs that are downregulated in prostate carcinoma. Int J Cancer 132, 775784.
23. Du, WW, Fang, L, Li, M, et al. (2013) MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling. J Cell Sci 126, 14401453.
24. Lin, SC, Liu, CJ, Lin, JA, et al. (2010) miR-24 up-regulation in oral carcinoma: positive association from clinical and in vitro analysis. Oral Oncol 46, 204208.
25. Liu, X, Wang, A, Heidbreder, CE, et al. (2010) MicroRNA-24 targeting RNA-binding protein DND1 in tongue squamous cell carcinoma. FEBS Lett 584, 41154120.
26. Qin, W, Shi, Y, Zhao, B, et al. (2010) miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS ONE 5, e9429.
27. Gu, J, Ahn-Jarvis, JH, Riedl, KM, et al. (2014) Characterization of black raspberry functional food products for cancer prevention human clinical trials. J Agric Food Chem 62, 39974006.
28. Wang, LS, Hecht, SS, Carmella, SG, et al. (2009) Anthocyanins in black raspberries prevent esophageal tumors in rats. Cancer Prev Res 2, 8493.
29. Montrose, DC, Horelik, NA, Madigan, JP, et al. (2011) Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative colitis. Carcinogenesis 32, 343350.
30. Pan, P, Skaer, CW, Stirdivant, SM, et al. (2015) Beneficial regulation of metabolic profiles by black raspberries in human colorectal cancer patients. Cancer Prev Res 8, 743750.
31. Coates, EM, Popa, G, Gill, CI, et al. (2007) Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer. J Carcinog 6, 4.
32. Bi, X, Fang, W, Wang, LS, et al. (2010) Black raspberries inhibit intestinal tumorigenesis in apc1638+/– and Muc2–/– mouse models of colorectal cancer. Cancer Prev Res 3, 14431450.
33. Xiao, T, Guo, Z, Bi, X, et al. (2017) Polyphenolic profile as well as anti-oxidant and anti-diabetes effects of extracts from freeze-dried black raspberries. J Funct Foods 31, 179187.
34. Stoner, GD, Wang, LS, Zikri, N, et al. (2007) Cancer prevention with freeze-dried berries and berry components. Semin Cancer Biol 17, 403410.
35. Bi, X, Tong, C, Dockendorff, A, et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis 29, 14351440.
36. Xuan, Y, Yang, H, Zhao, L, et al. (2015) MicroRNAs in colorectal cancer: small molecules with big functions. Cancer Lett 360, 89105.
37. Zhang, H, Zhu, YQ, Wu, YQ, et al. (2014) Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer. World J Gastroenterol 20, 63296335.
38. Li, J, Zhang, D, Stoner, GD, et al. (2008) Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes. Mol Carcinog 47, 286294.
39. Chen, L, Jiang, B, Zhong, C, et al. (2018) Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation. Carcinogenesis 39, 471481.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed