DOI QR코드

DOI QR Code

Expression and Clinical Significance of miRNA-34a in Colorectal Cancer

  • Ma, Zhi-Bin (Department of Gastroenterology, the First Affiliated Hospital of Harbin Medical University) ;
  • Kong, Xiao-Lin (Department of Hematology, the First Affiliated Hospital of Harbin Medical University) ;
  • Cui, Gang (Department of Hematology, the First Affiliated Hospital of Harbin Medical University) ;
  • Ren, Cui-Cui (Department of Hematology, the First Affiliated Hospital of Harbin Medical University) ;
  • Zhang, Ying-Jie (Department of Hematology, the First Affiliated Hospital of Harbin Medical University) ;
  • Fan, Sheng-Jin (Department of Hematology, the First Affiliated Hospital of Harbin Medical University) ;
  • Li, Ying-Hua (Department of Hematology, the First Affiliated Hospital of Harbin Medical University)
  • Published : 2014.11.28

Abstract

Background: The aim of this study was to investigate differences of miRNA-34a expression in benign and malignant colorectal lesions. Materials and Methods: Samples of cancer, paraneoplastic tissues and polyps were selected and total RNA was extracted by conventional methods for real-time PCR to detect the miRNA-34a expression. In addition, the LOVO colorectal cancer cell line was cultured, treated with the demethylating agent 5-azacytidine and screened for differentially expressed miRNA-34a. Results: After the drug treatment, the miRNA-34a expression of colorectal cancer cell line LOVO was increased and real-time PCR showed that levels of expression in both cell line and colorectal cancer tissues were low, as compared to paraneoplastic tissue (p<0.05). Polyps tissues had significantly higher expression than paraneoplastic and colorectal cancer samples (p<0.05). Conclusions: miRNA-34a-5p may play a role as a tumor suppressor gene in colorectal cancer, with involvement of DNA methylation.

Keywords

References

  1. Aranha MM, Santos DM, Sola S, Steer CJ, Rodrigues CM (2011). miR-34a regulates mouse neural stem cell differentiation. PloS One, 6, 21396. https://doi.org/10.1371/journal.pone.0021396
  2. Bao N, Lye KW, Barton MK (2004). MicroRNA binding sites in Arabidopsis class III HD-ZIP mRNAs are required for methylation of the template chromosome. Dev Cell, 7, 653-62. https://doi.org/10.1016/j.devcel.2004.10.003
  3. Bartel DP (2009). MicroRNAs: Target recognition and regulatory functions. Cell, 136, 215-33. https://doi.org/10.1016/j.cell.2009.01.002
  4. Calin GA, Sevignani C, Dumitru CD, et al (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA, 101, 2999-3004. https://doi.org/10.1073/pnas.0307323101
  5. Chang TC, Wentzel EA, Kent OA, et al (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell, 26, 745-52. https://doi.org/10.1016/j.molcel.2007.05.010
  6. Corte H, Manceau G, Blons H, et al (2012). MicroRNA and colorectal cancer. Dig Liver Dis, 44, 195-200. https://doi.org/10.1016/j.dld.2011.10.010
  7. Giraldez MD, Lozano JJ, Ramirez G, et al (2013). Circulating microRNAs as biomarkers of colorectal cancer: results from a genome-wide profiling and validation study. Clin Gastroenterol Hepatol, 11, 681-8. https://doi.org/10.1016/j.cgh.2012.12.009
  8. Grady WM, Parkin RK, Mitchell PS, et al (2008). Epigenetic silencing of the intronic microRNA has-miR-342 and its host gene EVL in colorectal cancer. Oncogene, 27, 3880-8. https://doi.org/10.1038/onc.2008.10
  9. Guessous F, Zhang Y, Kofman A, et al (2010). miRNA-34a-5p is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle, 9, 1031-6. https://doi.org/10.4161/cc.9.6.10987
  10. He L, He X, Lim LP, et al (2007a). A microRNA component of the p53 tumour suppressor network. Nature, 447, 1130-4. https://doi.org/10.1038/nature05939
  11. He L, He X, Lowe SW, Hannon GJ (2007b). MicroRNAs join the p53 network-another piece in the tumour suppression puzzle. Nat Rev Cancer, 7, 819-22. https://doi.org/10.1038/nrc2232
  12. He X, He L, Hannon GJ (2007c). The guardian's little helper: Micro-RNAs in the p53 tumor suppressor network. Cancer Res, 67, 11099-101. https://doi.org/10.1158/0008-5472.CAN-07-2672
  13. Hermeking H (2010). The miR-34 family in cancer and apoptosis. Cell Death Differ, 17, 193-9. https://doi.org/10.1038/cdd.2009.56
  14. Kanaan Z, Rai SN, Eichenberger MR, et al (2012). Plasma miR-21: a potential diagnostic marker of colorectal cancer. Ann Surg, 256, 544-51. https://doi.org/10.1097/SLA.0b013e318265bd6f
  15. Kim HC, Lee HJ, Roh SA, et al (2008). CpG island methylation in familial colorectal cancer patients not fulf illing the Amsterdam criteria. J Korean Med Sci, 23, 270-7. https://doi.org/10.3346/jkms.2008.23.2.270
  16. Kumar K, Brim H, Giardiello F, et al (2009). Distinct BRAF (V600E) and KRAS mutations in high microsatellite instability sporadic colorectal cancer in African Americans. Clin Cancer Res, 15, 1155-61. https://doi.org/10.1158/1078-0432.CCR-08-1029
  17. Liu C, Kelnar RK, Liu B, et al (2011). The microRNA miR34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med, 17, 211-5. https://doi.org/10.1038/nm.2284
  18. Raver-Shapira N, Marciano E, Meiri E, et al (2007). Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell, 26, 731-43. https://doi.org/10.1016/j.molcel.2007.05.017
  19. Schimanski CC, Frerichs K, Rahman F, et al (2009). High miR-196a levels promote the Oncogenic phenotype of colorectal cancer cells. World J Gastroenterol, 15, 2089-96. https://doi.org/10.3748/wjg.15.2089
  20. Tarasov V, Jung P, Verdoodt B, et al (2007). Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle, 6, 1586-93. https://doi.org/10.4161/cc.6.13.4436
  21. Tazawa H, Tsuchiya N, Izumiya M, Nakagama H (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 USA, 104, 15472-7. https://doi.org/10.1073/pnas.0707351104
  22. Toyota M, Suguki H, Sasaki Y, et al (2008). Epigenetic silencing of microRNA-34b/c and B-cell translocation gene4 is associated with CpG island methylation in colorectal cancer. Cancer Res, 68, 4123-32. https://doi.org/10.1158/0008-5472.CAN-08-0325
  23. Vilkin A, Niv Y, Nagasaka T, et al (2009). Microsatellite in stability, MLH 1 promoter methylation, and BRAF mutat ion analys is in sporad ic colorectal cancers of d ifferent ethn ic groups in Israel. Cancer, 115, 760-9. https://doi.org/10.1002/cncr.24019
  24. Vinall RL, Ripoll AZ, Wang S, Pan CX, deVere White RW (2012). MiR-34a chemosensitizes bladder cancer cells to cisplatin treatment regardless of P53-Rb pathway status. Int J Cancer, 130, 2526-38. https://doi.org/10.1002/ijc.26256
  25. Vire E, Brenner C, Deplus R, et al (2006) The Polycomb group protein EZH 2 directly controls DNA methylation. Nature, 439, 871-4.
  26. Weber B, Stresemann C, Brueckner B, Lyko F (2007). Methylation of human microRNA genes in normal and neolastic cells. Cell Cycle, 6, 1001-5. https://doi.org/10.4161/cc.6.9.4209
  27. Welch C, Chen Y, Stallings RL (2007). MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene, 26, 5017-22. https://doi.org/10.1038/sj.onc.1210293
  28. Wu CW, Ng SS, Dong YJ, et al (2012). Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut, 61, 739-45. https://doi.org/10.1136/gut.2011.239236
  29. Yamakuchi M, Lowenstein CJ (2009). MiR-34, SIRT1 and P53: the feedback loop. Cell Cycle, 8, 712-5. https://doi.org/10.4161/cc.8.5.7753
  30. Zanette DL, Rivadavia F, Molfetta GA, et al (2007). miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res, 40, 1435-40. https://doi.org/10.1590/S0100-879X2007001100003
  31. Zhou T, Zhang G, Liu Z, et al (2013). Overexpression of miR-92a correlates with tumor metastasis and poor prognosis in patients with colorectal cancer. Int J Colorectal Dis, 28, 19-24. https://doi.org/10.1007/s00384-012-1528-1
  32. Zhou XJ, Dong ZG, Yang YM, et al (2013). Limited diagnostic value of microRNAs for detecting colorectal cancer: A Meta-analysis. Asian Pac J Cancer Prev, 14, 4699-704. https://doi.org/10.7314/APJCP.2013.14.8.4699

Cited by

  1. microRNA Expression Profile in Patients with Stage II Colorectal Cancer: A Turkish Referral Center Study vol.16, pp.5, 2015, https://doi.org/10.7314/APJCP.2015.16.5.1851
  2. miRNA-34a-5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis vol.16, pp.6, 2017, https://doi.org/10.3892/mmr.2017.7677