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Suppression of lung cancer metastasis-related protein 1 (LCMR1) inhibits the growth of colorectal cancer cells

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Abstract

Lung cancer metastasis-related protein 1 (LCMR1) is a critical subunit of the mediator complex, and plays an important role in the elaborate regulation of gene transcription. However, the functional role of LCMR1 in colorectal carcinoma (CRC) has not been clarified. In this study, LCMR1 expression in CRC specimens was quantified by using the quantitative reverse transcription polymerase chain reaction method. The effect of downregulation of LCMR1 by lentivirus-mediated small hairpin RNA (shRNA) on CRC cell proliferation and tumorigenesis was explored. There was a higher expression of LCMR1 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.05). LCMR1 gene was effectively knocked down in human CRC RKO and DLD-1 cells that infected with lentivirus delivering shRNA against LCMR1, which resulted in inhibition of cell proliferation and augmentation of G0/G1 phase proportion. Moreover, the tumorigenicity of RKO cells was also dramatically inhibited after LCMR1 was knocked down. In conclusion, our results suggest that LCMR1 promotes CRC cell growth, and lentivirus-mediated silencing of LCMR1 may contribute to the gene therapy for CRC.

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References

  1. Boube M, Joulia L, Cribbs DL, Bourbon HM (2002) Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell 110:143–151

    Article  PubMed  CAS  Google Scholar 

  2. Chadick JZ, Asturias FJ (2005) Structure of eukaryotic mediator complexes. Trends Biochem Sci 30:264–271

    Article  PubMed  CAS  Google Scholar 

  3. Rosenblum-Vos LS, Rhodes L, Evangelista CC Jr, Boayke KA, Zitomer RS (1991) The ROX3 gene encodes an essential nuclear protein involved in CYC7 gene expression in Saccharomyces cerevisiae. Mol Cell Biol 11:5639–5647

    PubMed  CAS  Google Scholar 

  4. Béve J, Hu GZ, Myers LC, Balciunas D, Werngren O, Hultenby K, Wibom R, Ronne H, Gustafsson CM (2005) The structural and functional role of Med5 in the yeast mediator tail module. J Biol Chem 280:41366–41372

    Article  PubMed  Google Scholar 

  5. Singh H, Erkine AM, Kremer SB, Duttweiler HM, Davis DA, Iqbal J, Gross RR, Gross DS (2006) A functional module of yeast mediator that governs the dynamic range of heat-shock gene expression. Genetics 172:2169–2184

    Article  PubMed  CAS  Google Scholar 

  6. Baidoobonso SM, Guidi BW, Myers LC (2007) LCMR1(Rox3) regulates intermodule interactions in the Saccharomyces cerevisiae mediator complex. J Biol Chem 282:5551–5559

    Article  PubMed  CAS  Google Scholar 

  7. Ding N, Tomomori-Sato C, Sato S, Conaway RC, Conaway JW, Boyer TG (2009) LCMR1 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression. J Biol Chem 284:2648–2656

    Article  PubMed  CAS  Google Scholar 

  8. Chen L, Liang Z, Tian Q, Li C, Ma X, Zhang Y, Yang Z, Wang P, Li Y (2011) Overexpression of LCMR1 is significantly associated with clinical stage in human NSCLC. J Exp Clin Cancer Res 30:18

    Article  PubMed  CAS  Google Scholar 

  9. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  10. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  11. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36

    Article  PubMed  Google Scholar 

  12. Pullmann R Jr, Juhaszova M, López de Silanes I, Kawai T, Mazan-Mamczarz K, Halushka MK, Gorospe M (2005) Enhanced proliferation of cultured human vascular smooth muscle cells linked to increased function of RNA-binding protein HuR. J Biol Chem 280:22819–22826

    Article  PubMed  CAS  Google Scholar 

  13. Zielske SP, Stevenson M (2005) Importin 7 may be dispensable for human immunodeficiency virus type 1 and simian immunodeficiency virus infection of primary macrophages. J Virol 79:11541–11546

    Article  PubMed  CAS  Google Scholar 

  14. Sakoda T, Kasahara N, Hamamori Y, Kedes L (1999) A high-titer lentiviral production system mediates efficient transduction of differentiated cells including beating cardiac myocytes. J Mol Cell Cardiol 31:2037–2047

    Article  PubMed  CAS  Google Scholar 

  15. Soneoka Y, Cannon PM, Ramsdale EE, Griffiths JC, Romano G, Kingsman SM, Kingsman AJ (1995) A transient three-plasmid expression system for the production of high titer retroviral vectors. Nucleic Acids Res 23:628–633

    Article  PubMed  CAS  Google Scholar 

  16. Lesch HP, Laitinen A, Peixoto C, Vicente T, Makkonen KE, Laitinen L, Pikkarainen JT, Samaranayake H, Alves PM, Carrondo MJ, Ylä-Herttuala S, Airenne KJ (2011) Production and purification of lentiviral vectors generated in 293T suspension cells with baculoviral vectors. Gene Ther. doi:10.1038/gt.2010.162

  17. Wilson R, Purcell D, Netter HJ, Revill PA (2009) Does RNA interference provide new hope for control of chronic hepatitis B infection? Antivir Ther 14:879–889

    Article  PubMed  CAS  Google Scholar 

  18. Berkhout B (2009) Toward a durable anti-HIV gene therapy based on RNA interference. Ann N Y Acad Sci 1175:3–14

    Article  PubMed  CAS  Google Scholar 

  19. Liu YP, Berkhout B (2009) Lentiviral delivery of RNAi effectors against HIV-1. Curr Top Med Chem 9:1130–1143

    Article  PubMed  CAS  Google Scholar 

  20. Subramanya S, Kim SS, Manjunath N, Shankar P (2010) RNA interference-based therapeutics for human immunodeficiency virus HIV-1 treatment: synthetic siRNA or vector-based shRNA? Expert Opin Biol Ther 10:201–213

    Article  PubMed  CAS  Google Scholar 

  21. Huang DD (2008) The potential of RNA interference-based therapies for viral infections. Curr HIV/AIDS Rep 5:33–39

    Article  PubMed  CAS  Google Scholar 

  22. Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8:129–138

    Article  PubMed  CAS  Google Scholar 

  23. Jankovic R, Radulovic S, Brankovic-Magic M (2009) siRNA and miRNA for the treatment of cancer. J Buon 14:S43–S49

    PubMed  Google Scholar 

  24. Quon K, Kassner PD (2009) RNA interference screening for the discovery of oncology targets. Expert Opin Ther Targets 13:1027–1035

    Article  PubMed  CAS  Google Scholar 

  25. Wang HJ, Zhu JS, Zhang Q, Guo H, Dai YH, Xiong XP (2009) RNAi-mediated silencing of ezrin gene reverses malignant behavior of human gastric cancer cell line SGC-7901. J Dig Dis 10:258–264

    Article  PubMed  CAS  Google Scholar 

  26. Lv W, Zhang C, Zhou DH, Hao J, Sun JG, Liu T, Hao YX, Yu PW (2007) RNAi-mediated gene silencing of vascular endothelial growth factor inhibits growth of colorectal cancer. Cancer Biother Radiopharm 22:841–852

    Article  PubMed  CAS  Google Scholar 

  27. Pardo FS, Su M, Borek C (1996) Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation. Somat Cell Mol Genet 22:135–144

    Article  PubMed  CAS  Google Scholar 

  28. 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

    Article  PubMed  CAS  Google Scholar 

  29. Conaway JW, Florens L, Sato S, Tomomori-Sato C, Parmely TJ, Yao T, Swanson SK, Banks CA, Washburn MP, Conaway RC (2005) The mammalian mediator complex. FEBS Lett 579:904–908

    Article  PubMed  CAS  Google Scholar 

  30. Manilla P, Rebello T, Afable C, Lu X, Slepushkin V, Humeau LM, Schonely K, Ni Y, Binder GK, Levine BL, MacGregor RR, June CH, Dropulic B (2005) Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector. Hum Gene Ther 16:17–25

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

The research was supported by a fund from the Science and Technology Commission of Shanghai Municipality (No: 07DZ1950).

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Correspondence to Chuan-Gang Fu.

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Ji-Fu, E., Xing, JJ., Hao, LQ. et al. Suppression of lung cancer metastasis-related protein 1 (LCMR1) inhibits the growth of colorectal cancer cells. Mol Biol Rep 39, 3675–3681 (2012). https://doi.org/10.1007/s11033-011-1142-2

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  • DOI: https://doi.org/10.1007/s11033-011-1142-2

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