Advertisement

Tumor Biology

, Volume 35, Issue 4, pp 2983–2988 | Cite as

Overexpression of miR-145 increases the sensitivity of vemurafenib in drug-resistant colo205 cell line

  • Wei Peng
  • Jian Hu
  • Xiao-dong Zhu
  • Xin Liu
  • Chen-chen Wang
  • Wen-hua Li
  • Zhi-yu Chen
Research Article

Abstract

Vemurafenib is a selective and potent small molecule inhibitor of the V600 mutant form of the BRAF protein used in the treatment of melanoma and colorectal cancer. However, vemurafenib has less effect in BRAF mutant colorectal cancer due to the resistance of tumor cell to vemurafenib. To verify whether or not miR-145, a short RNA molecule of microRNA which has been supposed to be a tumor suppressor, is involved in this process, we established vemurafenib-resistant cell line colo205/V and found that the miR-145 expression was significantly downregulated in colo205/V cells compared to normal colo205 cells. Moreover, the overexpression of miR-145 could increase the sensitivity of colo205/V cells to vemurafenib both in vitro and in vivo. In conclusion, miR-145 might be used as a therapeutic target in the treatment of colorectal cancer patients with BRAF V600E mutation.

Keywords

miR-145 colo205 Drug resistance Vemurafenib 

Notes

Conflicts of interest

None

References

  1. 1.
    Cunningham D, Atkin W, Lenz HJ, et al. Colorectal cancer. Lancet. 2010;375:1030–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Bray F, Center MM, Ferlay J, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRefGoogle Scholar
  3. 3.
    Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27:3677–83.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.PubMedCrossRefGoogle Scholar
  5. 5.
    Di Nicolantonio F, Martini M, Molinari F, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26:5705–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Nikiforova MN, Kimura ET, Gandhi M, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003;88:5399–404.PubMedCrossRefGoogle Scholar
  7. 7.
    Kimura ET, Nikiforova MN, Zhu Z, et al. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 2003;63:1454–7.PubMedGoogle Scholar
  8. 8.
    Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 2004;116:855–67.PubMedCrossRefGoogle Scholar
  9. 9.
    McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007;1773:1263–84.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004;4:937–47.PubMedCrossRefGoogle Scholar
  11. 11.
    Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med. 2009;361:98–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117:4623–32.PubMedCrossRefGoogle Scholar
  13. 13.
    Bollag G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010;467:596–9.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Tsai J, Lee JT, Wang W, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A. 2008;105:3041–6.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363:809–19.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483:100–3.PubMedCrossRefGoogle Scholar
  18. 18.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMedCrossRefGoogle Scholar
  19. 19.
    Berezikov E, Guryev V, van de Belt J, et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005;120:21–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhang B, Pan X, Cobb GP, et al. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.PubMedCrossRefGoogle Scholar
  21. 21.
    Yu PN, Yan MD, Lai HC, et al. Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells. Int J Cancer. 2013. http://www.ncbi.nlm.nih.gov/pubmed/23904094.
  22. 22.
    Shang Y, Zhang Z, Liu Z, et al. miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene. 2013. http://www.ncbi.nlm.nih.gov/pubmed/23893241.
  23. 23.
    Pagliuca A, Valvo C, Fabrizi E, et al. Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression. Oncogene. 2013;32:4806–13.Google Scholar
  24. 24.
    Gotte M, Mohr C, Koo CY, et al. miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness. Oncogene. 2010;29:6569–80.PubMedCrossRefGoogle Scholar
  25. 25.
    Sachdeva M, Zhu S, Wu F, et al. p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A. 2009;106:3207–12.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Cho WC, Chow AS, Au JS. MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1. RNA Biol. 2011;8:125–31.PubMedCrossRefGoogle Scholar
  27. 27.
    Gregersen LH, Jacobsen AB, Frankel LB, et al. MicroRNA-145 targets YES and STAT1 in colon cancer cells. PLoS One. 2010;5:e8836.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Chiyomaru T, Enokida H, Tatarano S, et al. miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer. 2010;102:883–91.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Shi M, Du L, Liu D, et al. Glucocorticoid regulation of a novel HPV-E6-p53-miR-145 pathway modulates invasion and therapy resistance of cervical cancer cells. J Pathol. 2012;228:148–57.PubMedCrossRefGoogle Scholar
  30. 30.
    Peltier HJ, Latham GJ. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA. 2008;14:844–52.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 1997;9:180–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nat Rev Mol Cell Biol. 2004;5:875–85.PubMedCrossRefGoogle Scholar
  33. 33.
    Bollag G, Tsai J, Zhang J, et al. Vemurafenib: the first drug approved for BRAF-mutant cancer. Nat Rev Drug Discov. 2012;11:873–86.PubMedCrossRefGoogle Scholar
  34. 34.
    Yang H, Higgins B, Kolinsky K, et al. Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer. Cancer Res. 2012;72:779–89.PubMedCrossRefGoogle Scholar
  35. 35.
    Adammek M, Greve B, Kassens N, et al. MicroRNA miR-145 inhibits proliferation, invasiveness, and stem cell phenotype of an in vitro endometriosis model by targeting multiple cytoskeletal elements and pluripotency factors. Fertil Steril. 2013;99:1346–55.PubMedCrossRefGoogle Scholar
  36. 36.
    Gao L, Ren W, Chang S, et al. Downregulation of miR-145 expression in oral squamous cell carcinomas and its clinical significance. Onkologie. 2013;36:194–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Avgeris M, Stravodimos K, Fragoulis EG, et al. The loss of the tumour-suppressor miR-145 results in the shorter disease-free survival of prostate cancer patients. Br J Cancer. 2013;108:2573–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Suh SO, Chen Y, Zaman MS, et al. MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer. Carcinogenesis. 2011;32:772–8.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Spizzo R, Nicoloso MS, Lupini L, et al. miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells. Cell Death Differ. 2010;17:246–54.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Wei Peng
    • 1
    • 2
  • Jian Hu
    • 3
  • Xiao-dong Zhu
    • 1
    • 2
  • Xin Liu
    • 1
    • 2
  • Chen-chen Wang
    • 1
    • 2
  • Wen-hua Li
    • 1
    • 2
  • Zhi-yu Chen
    • 1
    • 2
  1. 1.Department of Medical OncologyFudan University Shanghai Cancer CenterShanghaiChina
  2. 2.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Department of GastroenterologyHospital No. 455 of the PLAShanghaiChina

Personalised recommendations