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Article

MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer

  • Authors:
    • Bomi Kwak
    • Dong Uk Kim
    • Tae Oh Kim
    • Heui-Soo Kim
    • Sang-Woo Kim
  • View Affiliations / Copyright

    Affiliations: Department of Biological Sciences, Pusan National University, Pusan 46241, Republic of Korea, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Pusan 47392, Republic of Korea
  • Pages: 1800-1808
    |
    Published online on: July 26, 2018
       https://doi.org/10.3892/ijo.2018.4505
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Abstract

The aberrant expression of microRNAs (miRNAs or miRs) has been shown to be associated with the development of various types of cancer, including colorectal cancer (CRC). The increased activation of the Wnt signaling pathway via the loss of the Wnt repressor, adenomatous polyposis coli (APC), is the hallmark of human CRC. In this study, we demonstrate that the activation of the Wnt/c-Myc axis inhibits the expression of the tumor suppressor, p53, via promoting the targeting of p53 by miR‑552. Our results revealed that the ectopic expression of miR‑552 enhanced cell proliferation, colony formation and resistance to drug-induced apoptosis, suggesting that this miRNA may function as an oncogene. We found that miR‑552 displayed oncogenic properties by directly targeting the p53 tumor suppressor. Of note, our genetic and pharmacological experiments revealed that the Wnt/β-catenin signaling pathway and its major downstream target, c-Myc (hereafter termed Myc), increased the miR‑552 levels, and chromatin immunoprecipitation (ChIP) assays revealed they carried out this function by directly binding to their binding sites in the miR‑552 promoter region. Given that the functional loss of APC, leading to abnormal Wnt signals, and the absence of p53 protein are common in CRC, these results suggest that miR‑552 may serve as an important link between these two events, and this warrants further investigation. Collectively, the data of this study suggest that the inhibition of miR‑552 may disconnect elevated Wnt signals from p53 suppression, providing a novel therapeutic strategy for patients with CRC with deregulated Wnt signaling.
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1 

Grothey A, Sargent D, Goldberg RM and Schmoll HJ: Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 22:1209–1214. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Fransén K, Klintenäs M, Osterström A, Dimberg J, Monstein HJ and Söderkvist P: Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis. 25:527–533. 2004. View Article : Google Scholar

3 

Basu S, Haase G and Ben-Ze'ev A: Wnt signaling in cancer stem cells and colon cancer metastasis. F1000Res. 2016, 5:https://doi.org/10.12688/f1000research.7579.1. View Article : Google Scholar

4 

Kang YJ, Park HJ, Chung HJ, Min HY, Park EJ, Lee MA, Shin Y and Lee SK: Wnt/β-catenin signaling mediates the antitumor activity of magnolol in colorectal cancer cells. Mol Pharmacol. 82:168–177. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Lu Y, Xie S, Zhang W, Zhang C, Gao C, Sun Q, Cai Y, Xu Z, Xiao M, Xu Y, et al: Twa1/Gid8 is a beta-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis. Cell Res. 27:1422–1440. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Najdi R, Holcombe RF and Waterman ML: Wnt signaling and colon carcinogenesis: Beyond APC. J Carcinog. 10:52011. View Article : Google Scholar : PubMed/NCBI

7 

Tetsu O and McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 398:422–426. 1999. View Article : Google Scholar : PubMed/NCBI

8 

You Z, Saims D, Chen S, Zhang Z, Guttridge DC, Guan KL, MacDougald OA, Brown AM, Evan G, Kitajewski J, et al: Wnt signaling promotes oncogenic transformation by inhibiting c-Myc-induced apoptosis. J Cell Biol. 157:429–440. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Morin PJ: beta-catenin signaling and cancer. Bioessays. 21:1021–1030. 1999. View Article : Google Scholar : PubMed/NCBI

10 

Rivlin N, Brosh R, Oren M and Rotter V: Mutations in the p53 tumor suppressor gene: Important milestones at the various steps of tumorigenesis. Genes Cancer. 2:466–474. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Marine JC, Francoz S, Maetens M, Wahl G, Toledo F and Lozano G: Keeping p53 in check: Essential and synergistic functions of Mdm2 and Mdm4. Cell Death Differ. 13:927–934. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Meek DW: The p53 response to DNA damage. DNA Repair (Amst). 3:1049–1056. 2004. View Article : Google Scholar

13 

Liebermann DA, Hoffman B and Vesely D: p53 induced growth arrest versus apoptosis and its modulation by survival cytokines. Cell Cycle. 6:166–170. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Giaccia AJ and Kastan MB: The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev. 12:2973–2983. 1998. View Article : Google Scholar : PubMed/NCBI

15 

Moll UM and Petrenko O: The MDM2-p53 interaction. Mol Cancer Res. 1:1001–1008. 2003.

16 

Al-Kuraya KS: KRAS and TP53 mutations in colorectal carcinoma. Saudi J Gastroenterol. 15:217–219. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Iacopetta B: TP53 mutation in colorectal cancer. Hum Mutat. 21:271–276. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Sadot E, Geiger B, Oren M and Ben-Ze'ev A: Down-regulation of beta-catenin by activated p53. Mol Cell Biol. 21:6768–6781. 2011. View Article : Google Scholar

19 

Riascos-Bernal DF, Chinnasamy P, Cao LL, Dunaway CM, Valenta T, Basler K and Sibinga NE: β-catenin C-terminal signals suppress p53 and are essential for artery formation. Nat Commun. 7:123892016. View Article : Google Scholar

20 

Griffiths-Jones S: The microRNA registry. Nucleic Acids Res. 32(Database issue): D109–D111. 2004. View Article : Google Scholar :

21 

Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI

22 

Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH and Kim VN: MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23:4051–4060. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Piriyapongsa J and Jordan IK: A family of human microRNA genes from miniature inverted-repeat transposable elements. PLoS One. 2:e2032007. View Article : Google Scholar : PubMed/NCBI

24 

Piriyapongsa J, Marino-Ramirez L and Jordan IK: Origin and evolution of human microRNAs from transposable elements. Genetics. 176:1323–1337. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Finnegan DJ: Retrotransposons. Curr Biol. 22:R432–R437. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Li M, Marin-Muller C, Bharadwaj U, Chow KH, Yao Q and Chen C: MicroRNAs: Control and loss of control in human physiology and disease. World J Surg. 33:667–684. 2009. View Article : Google Scholar

27 

Lytle JR, Yario TA and Steitz JA: Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′UTR. Proc Natl Acad Sci USA. 104:9667–9672. 2007. View Article : Google Scholar

28 

Jansson MD and Lund AH: MicroRNA and cancer. Mol Oncol. 6:590–610. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Wu WK, Law PT, Lee CW, Cho CH, Fan D, Wu K, Yu J and Sung JJ: MicroRNA in colorectal cancer: From benchtop to bedside. Carcinogenesis. 32:247–253. 2011. View Article : Google Scholar

30 

Cao J, Yan XR, Liu T, Han XB, Yu JJ, Liu SH and Wang LB: MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/beta-catenin signaling pathway in colorectal cancer. Oncol Lett. 14:3795–802. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Wang J, Li H, Wang Y, Wang L, Yan X, Zhang D, Ma X, Du Y, Liu X and Yang Y: MicroRNA-552 enhances metastatic capacity of colorectal cancer cells by targeting a disintegrin and metalloprotease 28. Oncotarget. 7:70194–7210. 2016.PubMed/NCBI

32 

Jeong D, Kim J, Nam J, Sun H, Lee YH, Lee TJ, Aguiar RC and Kim SW: MicroRNA-124 links p53 to the NF-κB pathway in B-cell lymphomas. Leukemia. 29:1868–1874. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

34 

Dalby B, Cates S, Harris A, Ohki EC, Tilkins ML, Price PJ and Ciccarone VC: Advanced transfection with Lipofectamine 2000 reagent: Primary neurons, siRNA, and high-throughput applications. Methods. 33:95–103. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Cho Y, Song SH, Lee JJ, Choi N, Kim CG, Dean A and Kim A: The role of transcriptional activator GATA-1 at human beta-globin HS2. Nucleic Acids Res. 36:4521–4528. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Wang N and Liu W: Increased expression of miR-552 acts as a potential predictor biomarker for poor prognosis of colorectal cancer. Eur Rev Med Pharmacol Sci. 22:412–416. 2018.PubMed/NCBI

37 

Rowan AJ, Lamlum H, Ilyas M, Wheeler J, Straub J, Papadopoulou A, Bicknell D, Bodmer WF and Tomlinson IP: APC mutations in sporadic colorectal tumors: A mutational 'hotspot' and interdependence of the 'two hits'. Proc Natl Acad Sci USA. 97:3352–3357. 2000. View Article : Google Scholar

38 

Kim NH, Cha YH, Kang SE, Lee Y, Lee I, Cha SY, Ryu JK, Na JM, Park C, Yoon HG, et al: p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells. Cell Cycle. 12:1578–1587. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Kim NH, Kim HS, Kim NG, Lee I, Choi HS, Li XY, Kang SE, Cha SY, Ryu JK, Na JM, et al: p53 and microRNA-34 are suppressors of canonical Wnt signaling. Sci Signal. 4:ra712011. View Article : Google Scholar : PubMed/NCBI

40 

Hermeking H: p53 enters the microRNA world. Cancer Cell. 12:414–418. 2007. View Article : Google Scholar : PubMed/NCBI

41 

Ha TY: The role of microRNAs in regulatory T cells and in the immune response. Immune Netw. 11:11–41. 2011. View Article : Google Scholar : PubMed/NCBI

42 

Schultz NA, Werner J, Willenbrock H, Roslind A, Giese N, Horn T, Wøjdemann M and Johansen JS: MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma. Mod Pathol. 25:1609–1622. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kwak B, Kim D, Kim T, Kim H and Kim S: MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer. Int J Oncol 53: 1800-1808, 2018.
APA
Kwak, B., Kim, D., Kim, T., Kim, H., & Kim, S. (2018). MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer. International Journal of Oncology, 53, 1800-1808. https://doi.org/10.3892/ijo.2018.4505
MLA
Kwak, B., Kim, D., Kim, T., Kim, H., Kim, S."MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer". International Journal of Oncology 53.4 (2018): 1800-1808.
Chicago
Kwak, B., Kim, D., Kim, T., Kim, H., Kim, S."MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer". International Journal of Oncology 53, no. 4 (2018): 1800-1808. https://doi.org/10.3892/ijo.2018.4505
Copy and paste a formatted citation
x
Spandidos Publications style
Kwak B, Kim D, Kim T, Kim H and Kim S: MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer. Int J Oncol 53: 1800-1808, 2018.
APA
Kwak, B., Kim, D., Kim, T., Kim, H., & Kim, S. (2018). MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer. International Journal of Oncology, 53, 1800-1808. https://doi.org/10.3892/ijo.2018.4505
MLA
Kwak, B., Kim, D., Kim, T., Kim, H., Kim, S."MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer". International Journal of Oncology 53.4 (2018): 1800-1808.
Chicago
Kwak, B., Kim, D., Kim, T., Kim, H., Kim, S."MicroRNA-552 links Wnt signaling to p53 tumor suppressor in colorectal cancer". International Journal of Oncology 53, no. 4 (2018): 1800-1808. https://doi.org/10.3892/ijo.2018.4505
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