Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells

  • Wei, Ling (Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute) ;
  • Wang, Xing-Wu (Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute) ;
  • Sun, Ju-Jie (Department of Pathology, Shandong Cancer Hospital and Institute) ;
  • Lv, Li-Yan (Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute) ;
  • Xie, Li (Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute) ;
  • Song, Xian-Rang (Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute)
  • Published : 2015.03.04
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Abstract

Mediator 19 (Med19) is a component of the mediator complex which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 plays important roles in cancer cell proliferation and tumorigenesis. The involvement of Med19 in sensitivity to the chemotherapeutic agent cisplatin was here investigated. We employed RNA interference to reduce Med19 expression in human non-small cell lung cancer (NSCLC) cell lines and analyzed their phenotypic changes. The results showed that after Med19 siRNA transfection, expression of Med19 mRNA and protein was dramatically reduced (p<0.05). Meanwhile, impaired growth potential, arrested cell cycle at G0/G1 phase and enhanced sensitivity to cisplatin were exhibited. Apoptosis and caspase-3 activity were increased when cells were exposed to Med19 siRNA and/or cisplatin. The present findings suggest that Med19 facilitates tumorigenic properties of NSCLC cells and knockdown of Med19 may be a rational therapeutic tool for lung cancer cisplatin sensitization.

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References

  1. Boube M, Joulia L, Cribbs DL, et al (2002). Evidence for a Mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell, 110, 143-51. https://doi.org/10.1016/S0092-8674(02)00830-9
  2. Casamassimi A, Napoli C (2007). Mediator complexes and eukaryotic transcription regulation: an overview. Biochimie, 89, 1439-46. https://doi.org/10.1016/j.biochi.2007.08.002
  3. Chen L, Liang Z, Tian Q, et al (2011). Overexpression of LCMR1 is significantly associated with clinical stage in human NSCLC. J Exp Clin Cancer Res, 30, 18. https://doi.org/10.1186/1756-9966-30-18
  4. Conaway JW, Florens L, Sato S, et al (2005). The mammalian Mediator complex. FEBS Lett, 579, 904-8. https://doi.org/10.1016/j.febslet.2004.11.031
  5. Conaway RC, Sato S, Tomomori-Sato C, et al (2005). The mammalian Mediator complex and its role in transcriptional regulation. Trends Biochem Sci, 30, 250-5. https://doi.org/10.1016/j.tibs.2005.03.002
  6. Cui X, Xu D, Lv C, et al (2011). Suppression of MED19 expression by shRNA induces inhibition of cell proliferation and tumorigenesis in human prostate cancer cells. BMB Rep, 44, 547-52. https://doi.org/10.5483/BMBRep.2011.44.8.547
  7. Fulda S, Debatin KM (2006). Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 25, 4798-811. https://doi.org/10.1038/sj.onc.1209608
  8. Galluzzi L, Senovilla L, Vitale I, et al (2012). Molecular mechanisms of cisplatin resistance. Oncogene, 31, 1869-83. https://doi.org/10.1038/onc.2011.384
  9. Jang RW, Le Maître A, Ding K, et al (2009). Quality-adjusted time without symptoms or toxicity analysis of adjuvant chemotherapy in non-small-cell lung cancer: an analysis of the national cancer institute of Canada clinical trials group JBR.10 trial. J Clin Oncol, 27, 4268-73. https://doi.org/10.1200/JCO.2008.20.5815
  10. Ji-Fu E, Xing JJ, Hao LQ, et al (2012). Suppression of lung cancer metastasis-related protein 1 (LCMR1) inhibits the growth of colorectal cancer cells. Mol Biol Rep, 39, 3675-81. https://doi.org/10.1007/s11033-011-1142-2
  11. Hu MD, Xu JC, Fan Y, et al (2012). Hypoxia-inducible factor 1 promoter-induced JAB1 overexpression enhances chemotherapeutic sensitivity of lung cancer cell line A549 in an anoxic environment. Asian Pac J Cancer Prev, 13, 2115-20. https://doi.org/10.7314/APJCP.2012.13.5.2115
  12. Khuri FR, Herbst RS, Fossella FV (2001). Emerging therapies in non-small-cell lung cancer. Ann Oncol, 12, 739-44. https://doi.org/10.1023/A:1011197500223
  13. Li HL, Huang DZ, Deng T, et al (2012). Overexpression of cyclin L2 inhibits growth and enhances chemosensitivity in human gastric cancer cells. Asian Pac J Cancer Prev, 13, 1425-30. https://doi.org/10.7314/APJCP.2012.13.4.1425
  14. Li LH, He J, Hua D, et al (2011). Lentivirus-mediated inhibition of Med19 suppresses growth of breast cancer cells in vitro. Cancer Chemother Pharmacol, 68, 207-15. https://doi.org/10.1007/s00280-010-1468-9
  15. Li XH, Fang DN, Zeng CM (2011). Knockdown of MED19 by short hairpin RNA-mediated gene silencing inhibits pancreatic cancer cell proliferation. Cancer Biother Radiopharm, 26, 495-501. https://doi.org/10.1089/cbr.2010.0863
  16. Malik S, Roeder RG (2005). Dynamic regulation of pol II transcription by the mammalian Mediator complex. Trends Biochem Sci, 30, 256-63. https://doi.org/10.1016/j.tibs.2005.03.009
  17. Mazumder S, Plesca D, Almasan A (2008). Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis. Methods Mol Biol, 414, 13-21.
  18. Rosell R, Cecere F, Santarpia M, et al (2006). Predicting the outcome of chemotherapy for lung cancer. Curr Opin Pharmacol, 6, 323-31. https://doi.org/10.1016/j.coph.2006.01.011
  19. Satyanarayana A, Hilton MB, Kaldis P (2008). p21 Inhibits Cdk1 in the absence of Cdk2 to maintain the G1/S phase DNA damage checkpoint. Mol Biol Cell, 19, 65-77. https://doi.org/10.1091/mbc.E07-06-0525
  20. Snigdha S, Smith ED, Prieto GA, et al (2012). Caspase-3 activation as a bifurcation point between plasticity and cell death. Neurosci Bull, 28, 14-24. https://doi.org/10.1007/s12264-012-1057-5
  21. Song W, Jiang R, Zhao CM (2012). Role of integrin-linked kinase in multi-drug resistance of human gastric carcinoma SGC7901/DDP cells. Asian Pac J Cancer Prev, 13, 5619-25. https://doi.org/10.7314/APJCP.2012.13.11.5619
  22. Sun M, Jiang R, Li JD, et al (2011). MED19 promotes proliferation and tumorigenesis of lung cancer. Mol Cell Biochem, 355, 27-33. https://doi.org/10.1007/s11010-011-0835-0
  23. Vojnic E, Mourao A, Seizl M, et al (2011). Structure and VP16 binding of the Mediator Med25 activator interaction domain. Nat Struct Mol Biol, 18, 404-9. https://doi.org/10.1038/nsmb.1997
  24. Wang JS, Ji AF, Wan HJ, et al (2012). Gene silencing of $\beta$-catenin by RNAi inhibits proliferation of human esophageal cancer cells by inducing G0/G1 cell cycle arrest. Asian Pac J Cancer Prev, 13, 2527-32. https://doi.org/10.7314/APJCP.2012.13.6.2527
  25. Wang T, Hao L, Feng Y, et al (2011). Knockdown of MED19 by lentivirus-mediated shRNA in human osteosarcoma cells inhibits cell proliferation by inducing cell cycle arrest in the G0/G1 phase. Oncol Res, 19, 193-201. https://doi.org/10.3727/096504011X12970940207760
  26. Wen H, Feng CC, Ding GX, et al (2013). Med19 promotes bone metastasis and invasiveness of bladder urothelial carcinoma via bone morphogenetic protein 2. Ann Diagn Pathol, 17, 259-64. https://doi.org/10.1016/j.anndiagpath.2012.11.004
  27. Xu LL, Guo SL, Ma SR, et al (2012). Mammalian mediator 19 mediates H1299 lung adenocarcinoma cell clone conformation, growth, and metastasis. Asian Pac J Cancer Prev, 13, 3695-700. https://doi.org/10.7314/APJCP.2012.13.8.3695
  28. Xu Y, Li C, Tian Q, et al (2012). Suppression of lung cancer metastasis-related protein 1 promotes apoptosis in lung cancer cells. Int J Mol Med, 30, 1481-6.
  29. Yu HG, Wei W, Xia LH, et al (2013). FBW7 upregulation enhances cisplatin cytotoxicity in non-small cell lung cancer cells. Asian Pac J Cancer Prev, 14, 6321-6. https://doi.org/10.7314/APJCP.2013.14.11.6321
  30. Yu W, Zhang Z, Min D, et al (2014). Mediator of RNA polymerase II transcription subunit 19 promotes osteosarcoma growth and metastasis and associates with prognosis. Eur J Cancer, 50, 1125-36. https://doi.org/10.1016/j.ejca.2014.01.030
  31. Zhang H, Jiang H, Wang W, et al (2012). Expression of Med19 in bladder cancer tissues and its role on bladder cancer cell growth. Urol Oncol, 30, 920-7. https://doi.org/10.1016/j.urolonc.2010.10.003
  32. Zhang HQ, He B, Fang N, et al (2013). Autophagy inhibition sensitizes cisplatin cytotoxicity in human gastric cancer cell line SGC7901. Asian Pac J Cancer Prev, 14, 4685-8. https://doi.org/10.7314/APJCP.2013.14.8.4685
  33. Zhu LJ, Yan WX, Chen ZW, et al (2013). Disruption of Mediator complex subunit 19 (Med19) inhibits cell growth and migration in tongue cancer. World J Surg Oncol, 11, 116. https://doi.org/10.1186/1477-7819-11-116
  34. Zou SW, Ai KX, Wang ZG, et al (2011). The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells. Acta Pharmacol Sin, 32, 354-60. https://doi.org/10.1038/aps.2010.223

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