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Clinical and Translational Oncology

, Volume 18, Issue 5, pp 449–456 | Cite as

MicroRNA-33b inhibits tumor cell growth and is associated with prognosis in colorectal cancer patients

  • W. Liao
  • C. Gu
  • A. Huang
  • J. Yao
  • R. SunEmail author
Research Article

Abstract

Purpose

To explore the role of miR-33b in colorectal cancer (CRC) and the correlation between its expression and prognosis.

Methods

The expressions of miR-33b between CRC tissues and normal tissues were measured by real-time PCR. The effects of miR-33b on cell proliferation and cell cycle progression were detected by MTT assay, colony formation assay and flow cytometry. The potential regulations of miR-33b on multiple genes expression were verified by Western blot. Furthermore, the association of miR-33b with CRC clinicopathologic features and prognosis was analyzed by Chi-squared test and Kaplan–Meier tests.

Results

MiR-33b was downregulated in CRC compared with normal colorectal samples and miR-33b inhibited tumor cell growth and induced cell cycle arrest. Western blot assays and correlation analysis showed that miR-33b could regulate multiple growth-related genes. Moreover, the expression of miR-33b was associated with TNM stage and tumor size, and CRC patients with high miR-33b expression had a better prognosis.

Conclusion

Our data suggest that miR-33b functions as a tumor suppressor gene in CRC through regulating cell proliferation and cell cycle.

Keywords

Colorectal cancer miR-33b Cell cycle Prognosis 

Supplementary material

12094_2015_1388_MOESM1_ESM.tif (306 kb)
Supplementary Figure 1 Binding sites of miR-33a and miR-33b in CDK6, CCND1 and Pim-1 3′-UTR. (TIFF 305 kb)

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Yang L, Parkin DM, Li L, Chen Y. Time trends in cancer mortality in China: 1987–1999. Int J Cancer. 2003;106(5):771–83.CrossRefPubMedGoogle Scholar
  3. 3.
    Sung JJY, Lau JYW, Goh KL, Leung WK. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 2005;6(11):871–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.CrossRefPubMedGoogle Scholar
  5. 5.
    Zhang L, Dong Y, Zhu N, Tsoi H, Zhao Z, Wu CW, et al. microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer. Mol Cancer. 2014;13:124.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rokavec M, Öner MG, Li H, Jackstadt R, Jiang L, Lodygin D, et al. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Investig. 2014;124(4):1853–67.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Xiang KM, Li XR. MiR-133b acts as a tumor suppressor and negatively regulates TBPL1 in colorectal cancer cells. Asian Pac J Cancer Prev. 2014;15(8):3767–72.CrossRefPubMedGoogle Scholar
  8. 8.
    Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328(5985):1566–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Cirera-Salinas D, Pauta M, Allen RM, Salerno AG, Ramírez CM, Chamorro-Jorganes A, et al. Mir-33 regulates cell proliferation and cell cycle progression. Cell Cycle. 2012;11(5):922–33.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Thomas M, Lange-Grunweller K, Weirauch U, Gutsch D, Aigner A, Grunweller A, et al. The proto-oncogene Pim-1 is a target of miR-33a. Oncogene. 2012;31(7):918–28.CrossRefPubMedGoogle Scholar
  11. 11.
    Ibrahim AF, Weirauch U, Thomas M, Grünweller A, Hartmann RK, Aigner A. MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res. 2011;71(15):5214–24.CrossRefPubMedGoogle Scholar
  12. 12.
    Sobin LH, Gospodarowicz MK, Wittekind Ch. TNM classification of malignant tumors. 7th ed. Oxford: Wiley-Blackwell; 2009.Google Scholar
  13. 13.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Davalos A, Goedeke L, Smibert P, Ramirez CM, Warrier NP, Andreo U, et al. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci USA. 2011;108(22):9232–7.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Miyachi K, Sawada Y, Shida Y, Sugawara A, Hisatomi H. Lipogenic gene expression profile in patients with gastric cancer. Mol Clin Oncol. 2013;1(5):825–7.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013;19(22):6173–82.CrossRefPubMedGoogle Scholar
  17. 17.
    Schafer KA. The cell cycle: a review. Vet Pathol. 1998;35(6):461–78 (Online).CrossRefPubMedGoogle Scholar
  18. 18.
    Nawijn MC, Alendar A, Berns A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer. 2011;11(1):23–34.CrossRefPubMedGoogle Scholar
  19. 19.
    Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshall SM, van Gils JM, et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature. 2011;478(7369):404–7.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ono K, Horie T, Nishino T, Baba O, Kuwabara Y, Yokode M, et al. MicroRNA-33a/b in lipid metabolism—novel “thrifty” models. Circ J. 2015;79(2):278–84.CrossRefPubMedGoogle Scholar
  21. 21.
    Giovannucci E. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr. 2007;86(3):836S–42S.Google Scholar
  22. 22.
    Zhao W, Guan J, Horswell R, Li W, Wang Y, Wu X, et al. HDL cholesterol and cancer risk among patients with type 2 diabetes. Diabetes Care. 2014;37(12):3196–203.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Strickler HD, Wylie-Rosett J, Rohan T, Hoover DR, Smoller S, Burk RD, et al. The relation of type 2 diabetes and cancer. Diabetes Technol Ther. 2001;3(2):263–74.CrossRefPubMedGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2015

Authors and Affiliations

  1. 1.Department of General Surgery, Jinshan HospitalFudan UniversityShanghaiPeople’s Republic of China

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