Computational prediction of Mycoplasma hominis proteins targeting in nucleus of host cell and their implication in prostate cancer etiology
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Abstract
Cancer has long been assumed to be a genetic disease. However, recent evidence supports the enigmatic connection of bacterial infection with the growth and development of various types of cancers. The cause and mechanism of the growth and development of prostate cancer due to Mycoplasma hominis remain unclear. Prostate cancer cells are infected and colonized by enteroinvasive M. hominis, which controls several factors that can affect prostate cancer growth in susceptible persons. We investigated M. hominis proteins targeting the nucleus of host cells and their implications in prostate cancer etiology. Many vital processes are controlled in the nucleus, where the proteins targeting M. hominis may have various potential implications. A total of 29/563 M. hominis proteins were predicted to target the nucleus of host cells. These include numerous proteins with the capability to alter normal growth activities. In conclusion, our results emphasize that various proteins of M. hominis targeted the nucleus of host cells and were involved in prostate cancer etiology through different mechanisms and strategies.
Keywords
Mycoplasma hominis Protein targeting In silico Host nucleus Prostate cancer EtiologyAbbreviations
- M. hominis
Mycoplasma hominis
- ORFs
Open reading frames
- NLS
Nuclear localization signal or sequence
- BaCeILo
Balanced subcellular localization
- LGT
Lateral gene transfer
Notes
Acknowledgments
The authors are thankful to the Deanship of the Scientific Research and Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Compliance with ethical standards
Conflicts of interest
None
Supplementary material
References
- 1.Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, Fan TJ, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012;338:120–3.CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Lanoix JP, Pluquet E, Lescure FX, Bentayeb H, Lecuyer E, Boutemy M, et al. Bacterial infection profiles in lung cancer patients with febrile neutropenia. BMC Infect Dis. 2011;11:183.CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Barykova YA, Logunov DY, Shmarov MM, Vinarov AZ, Fiev DN, Vinarova NA, et al. Association of Mycoplasma hominis infection with prostate cancer. Oncotarget. 2011;2:289–97.CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Razin S, Yogev D, Naot Y. Molecular biology and pathogenicity of mycoplasmas. Microbiol Mol Biol Rev. 1998;62:1094–156.PubMedPubMedCentralGoogle Scholar
- 5.Huang S, Li JY, Wu J, Meng L, Shou CC. Mycoplasma infections and different human carcinomas. World J Gastroenterol. 2001;7:266–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Cimolai N. Do mycoplasmas cause human cancer? Can J Microbiol. 2001;47:691–7.CrossRefPubMedGoogle Scholar
- 7.Barykova Iu A, Shmarov MM, Logunov D, Verkhovskaia LV, Aliaev Iu G, Fiev DN, et al. [Identification of Mycoplasma in patients with suspected prostate cancer]. Zh Mikrobiol Epidemiol Immunobiol 2010:81–5.Google Scholar
- 8.Lo SC, Tsai S. Mycoplasmas and human prostate cancer: an exciting but cautionary note. Oncotarget. 2011;2:352–5.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Feng SH, Tsai S, Rodriguez J, Lo SC. Mycoplasmal infections prevent apoptosis and induce malignant transformation of interleukin-3-dependent 32D hematopoietic cells. Mol Cell Biol. 1999;19:7995–8002.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Tsai S, Wear DJ, Shih JW, Lo SC. Mycoplasmas and oncogenesis: persistent infection and multistage malignant transformation. Proc Natl Acad Sci U S A. 1995;92:10197–201.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7:256–69.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Sfanos KS, De Marzo AM. Prostate cancer and inflammation: the evidence. Histopathology. 2012;60:199–215.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Ito K. Prostate cancer in Asian men. Nat Rev Urol. 2014;11:197–212.CrossRefPubMedGoogle Scholar
- 14.Dessi D, Delogu G, Emonte E, Catania MR, Fiori PL, Rappelli P. Long-term survival and intracellular replication of Mycoplasma hominis in Trichomonas vaginalis cells: potential role of the protozoon in transmitting bacterial infection. Infect Immun. 2005;73:1180–6.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Namiki K, Goodison S, Porvasnik S, Allan RW, Iczkowski KA, Urbanek C, et al. Persistent exposure to Mycoplasma induces malignant transformation of human prostate cells. PLoS One. 2009;4, e6872.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Apweiler R, Bairoch A, Wu CH, Barker WC, Boeckmann B, Ferro S, et al. UniProt: the universal protein knowledgebase. Nucleic Acids Res. 2004;32:D115–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, et al. The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res. 2003;31:365–70.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Wu CH, Yeh LS, Huang H, Arminski L, Castro-Alvear J, Chen Y, et al. The protein information resource. Nucleic Acids Res. 2003;31:345–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Consortium U. Update on activities at the Universal Protein Resource (UniProt) in 2013. Nucleic Acids Res. 2013;41:D43–7.CrossRefGoogle Scholar
- 20.Pereyre S, Sirand-Pugnet P, Beven L, Charron A, Renaudin H, Barre A, et al. Life on arginine for Mycoplasma hominis: clues from its minimal genome and comparison with other human urogenital mycoplasmas. PLoS Genet. 2009;5, e1000677.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Kosugi S, Hasebe M, Tomita M, Yanagawa H. Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci U S A. 2009;106:10171–6.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Pierleoni A, Martelli PL, Fariselli P, Casadio R. BaCelLo: a balanced subcellular localization predictor. Bioinformatics. 2006;22:e408–16.CrossRefPubMedGoogle Scholar
- 23.Tran EJ, Wente SR. Dynamic nuclear pore complexes: life on the edge. Cell. 2006;125:1041–53.CrossRefPubMedGoogle Scholar
- 24.Khan S. Potential role of Escherichia coli DNA mismatch repair proteins in colon cancer. Crit Rev Oncol Hematol 2015.Google Scholar
- 25.Karin M, Lawrence T, Nizet V. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell. 2006;124:823–35.CrossRefPubMedGoogle Scholar
- 26.Sutcliffe S, Platz EA. Inflammation and prostate cancer: a focus on infections. Curr Urol Rep. 2008;9:243–9.CrossRefPubMedGoogle Scholar
- 27.Poutahidis T, Cappelle K, Levkovich T, Lee CW, Doulberis M, Ge Z, et al. Pathogenic intestinal bacteria enhance prostate cancer development via systemic activation of immune cells in mice. PLoS One. 2013;8, e73933.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, et al. Global analysis of protein localization in budding yeast. Nature. 2003;425:686–91.CrossRefPubMedGoogle Scholar
- 29.Garg A, Bhasin M, Raghava GP. Support vector machine-based method for subcellular localization of human proteins using amino acid compositions, their order, and similarity search. J Biol Chem. 2005;280:14427–32.CrossRefPubMedGoogle Scholar
- 30.Kumar M, Raghava GP. Prediction of nuclear proteins using SVM and HMM models. BMC Bioinforma. 2009;10:22.CrossRefGoogle Scholar
- 31.Su EC, Chang JM, Cheng CW, Sung TY, Hsu WL. Prediction of nuclear proteins using nuclear translocation signals proposed by probabilistic latent semantic indexing. BMC Bioinforma. 2012;13 Suppl 17:S13.CrossRefGoogle Scholar
- 32.Lange A, Mills RE, Lange CJ, Stewart M, Devine SE, Corbett AH. Classical nuclear localization signals: definition, function, and interaction with importin alpha. J Biol Chem. 2007;282:5101–5.CrossRefPubMedGoogle Scholar
- 33.Kosugi S, Hasebe M, Entani T, Takayama S, Tomita M, Yanagawa H. Design of peptide inhibitors for the importin alpha/beta nuclear import pathway by activity-based profiling. Chem Biol. 2008;15:940–9.CrossRefPubMedGoogle Scholar
- 34.Kosugi S, Hasebe M, Matsumura N, Takashima H, Miyamoto-Sato E, Tomita M, et al. Six classes of nuclear localization signals specific to different binding grooves of importin alpha. J Biol Chem. 2009;284:478–85.CrossRefPubMedGoogle Scholar
- 35.Hopfe M, Deenen R, Degrandi D, Kohrer K, Henrich B. Host cell responses to persistent mycoplasmas—different stages in infection of HeLa cells with Mycoplasma hominis. PLoS One. 2013;8, e54219.CrossRefPubMedPubMedCentralGoogle Scholar
- 36.Logunov DY, Scheblyakov DV, Zubkova OV, Shmarov MM, Rakovskaya IV, Gurova KV, et al. Mycoplasma infection suppresses p53, activates NF-kappaB and cooperates with oncogenic Ras in rodent fibroblast transformation. Oncogene. 2008;27:4521–31.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Suzuki M, Takahashi T. Aberrant DNA replication in cancer. Mutat Res 2013; 743–744:111–7.Google Scholar
- 38.Parry L, Clarke AR. The roles of the methyl-CpG binding proteins in cancer. Genes Cancer. 2011;2:618–30.CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Kattan Z, Marchal S, Brunner E, Ramacci C, Leroux A, Merlin JL, et al. Damaged DNA binding protein 2 plays a role in breast cancer cell growth. PLoS One. 2008;3, e2002.CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Wu X, Zhu Z, Li W, Fu X, Su D, Fu L, et al. Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer. Breast Cancer Res. 2012;14:R73.CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Maw MK, Fujimoto J, Tamaya T. Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers. BMC Cancer. 2009;9:430.CrossRefPubMedPubMedCentralGoogle Scholar
- 42.Strickertsson JA, Desler C, Rasmussen LJ. Impact of bacterial infections on aging and cancer: impairment of DNA repair and mitochondrial function of host cells. Exp Gerontol. 2014;56:164–74.CrossRefPubMedGoogle Scholar
- 43.Zhang B, Shih JW, Wear DJ, Tsai S, Lo SC. High-level expression of H-ras and c-myc oncogenes in mycoplasma-mediated malignant cell transformation. Proc Soc Exp Biol Med. 1997;214:359–66.CrossRefPubMedGoogle Scholar
- 44.Yang J, Hooper WC, Phillips DJ, Tondella ML, Talkington DF. Induction of proinflammatory cytokines in human lung epithelial cells during Chlamydia pneumoniae infection. Infect Immun. 2003;71:614–20.CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Mote Jr J, Reines D. Recognition of a human arrest site is conserved between RNA polymerase II and prokaryotic RNA polymerases. J Biol Chem. 1998;273:16843–52.CrossRefPubMedPubMedCentralGoogle Scholar
- 46.Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Transcription termination. In: In Molecular Cell Biology. New York: W.H. Freeman, 2000.Google Scholar
- 47.Garnis C, Buys TP, Lam WL. Genetic alteration and gene expression modulation during cancer progression. Mol Cancer. 2004;3:9.CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Libermann TA, Zerbini LF. Targeting transcription factors for cancer gene therapy. Curr Gene Ther. 2006;6:17–33.CrossRefPubMedGoogle Scholar
- 49.Riley DR, Sieber KB, Robinson KM, White JR, Ganesan A, Nourbakhsh S, et al. Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples. PLoS Comput Biol. 2013;9, e1003107.CrossRefPubMedPubMedCentralGoogle Scholar
- 50.Dunning Hotopp JC. Horizontal gene transfer between bacteria and animals. Trends Genet. 2012;27:157–63.CrossRefGoogle Scholar
- 51.Khan AA, Shrivastava A. Bacterial infections associated with cancer: possible implication in etiology with special reference to lateral gene transfer. Cancer Metastasis Rev. 2010;29:331–7.CrossRefPubMedGoogle Scholar