Advertisement

Interaction network analysis of YBX1 for identification of therapeutic targets in adenocarcinomas

  • Suriya Narayanan Murugesan
  • Birendra Singh Yadav
  • Pramod Kumar Maurya
  • Amit Chaudhary
  • Swati Singh
  • Ashutosh ManiEmail author
Article
  • 9 Downloads

Abstract

Human Y-box binding protein-1 (YBX1) is a member of highly conserved cold-shock domain protein family, which is involved in transcriptional as well as translational regulation of many genes. Nuclear localization of YBX1 has been observed in various cancer types and it’s overexpression has been linked to adverse clinical outcome and poor therapy response, but no diagnostic or therapeutic correlation has been established so far. This study aimed to identify differentially expressed novel genes among the interactors of YBX1 in different cancer types. Analysis of RNA-Seq data for colorectal, lung, prostate and stomach adenocarcinoma identified 39 unique genes, which are differentially expressed in the four adenocarcinoma types. Gene-enrichment analysis for the differentially expressed genes from individual adenocarcinoma with focus on unique genes resulted in a total of 57 gene sets specific to each adenocarcinoma. Gene ontology for commonly expressed genes suggested the pathways and possible mechanisms through which they affect each adenocarcinoma type considered in the study. Gene regulatory network constructed for the common genes and network topology was analyzed for the central nodes. Here 12 genes were found to play important roles in the network formation; among them, two genes FOXM1 and TOP2A were found to be in central network formation, which makes them a common target for therapeutics. Furthermore, five common differentially expressed genes in all adenocarcinomas were also identified.

Keywords

Adenocarcinoma regulatory network RNA-Seq YBX1 

Notes

Acknowledgements

AM acknowledges SERB, New Delhi for a project grant under the young scientist scheme.

Supplementary material

12038_2019_9848_MOESM1_ESM.pdf (132 kb)
Supplementary material 1 (PDF 131 kb)
12038_2019_9848_MOESM2_ESM.pdf (508 kb)
Supplementary material 2 (PDF 507 kb)
12038_2019_9848_MOESM3_ESM.xlsx (22 kb)
Supplementary material 3 (XLSX 22 kb)
12038_2019_9848_MOESM4_ESM.xlsx (38 kb)
Supplementary material 4 (XLSX 37 kb)
12038_2019_9848_MOESM5_ESM.txt (1 kb)
Supplementary material 5 (TXT 0 kb)
12038_2019_9848_MOESM6_ESM.txt (3 kb)
Supplementary material 6 (TXT 2 kb)

References

  1. Ashizuka M, Fukuda T, Nakamura T, Shirasuna K, Iwai K, Izumi H and Uchiumi T 2002 Novel translational control through an iron-responsive element by interaction of multifunctional protein YB-1 and IRP2. Mol. Cell. Biol. 22 6375–6383CrossRefGoogle Scholar
  2. Barabasi AL and Oltvai ZN 2004 Network biology: understanding the cell’s functional organization. Nat. Rev. Genet. 5 101–113CrossRefGoogle Scholar
  3. Bargou R, Jurchott K, Wargener C, Bergmann S, Metzner S, Bommert K, Dorken B and Royer H 1997 Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nat. Med. 3 447–450CrossRefGoogle Scholar
  4. Brentani H, Caballero OL, Camargo AA, da Silva AM, da Silva WA Jr, Dias Neto E and Zalcberg H 2003 The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags. PNAS 100 13418–13423CrossRefGoogle Scholar
  5. Chernukhin IV, Shamsuddin S, Robinson AF, Carne AF, Paul A, El-kady AI and Klenova EM 2000 Physical and functional interaction between two pluripotent proteins, the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF. J. Biol. Chem. 275 29915–29921CrossRefGoogle Scholar
  6. Cordell HJ 2009 Detecting gene–gene interactions that underlie human diseases. Nat. Rev. Genet. 10 392–404CrossRefGoogle Scholar
  7. Eliseeva IA, Kim ER, Guryanov SG, Ovchinnikov LP and Lyabin DN 2011 Y Box binding protein 1 (YB 1) and its functions. Biochemistry 76 1402–1433PubMedGoogle Scholar
  8. Fang X, Cai Y, Liu J, Wang Z, Wu Q, Zhang Z and Ouyang G 2011 Twist2 contributes to breast cancer progression by promoting an epithelial–mesenchymal transition and cancer stem-like cell self-renewal. Oncogene 30 4707–4720CrossRefGoogle Scholar
  9. Furlong LI 2013 Human diseases through the lens of network biology. TL – 29. Trends Genet 29 150–159CrossRefGoogle Scholar
  10. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S and Zhang J 2004 Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5 R80CrossRefGoogle Scholar
  11. Hahn MW and Kern AD 2004 Comparative genomics of centrality and essentiality in three eukaryotic protein-interaction networks. Mol. Biol. Evol. 22 803–806CrossRefGoogle Scholar
  12. Halasi M and Gartel AL 2013 Targeting FOXM1 in cancer. Biochem. Pharmacol. 85 644–652CrossRefGoogle Scholar
  13. Han H, Shim H, Shin D, Shim JE, Ko Y, Shin J and Lee I 2015 TRRUST: a reference database of human transcriptional regulatory interactions. Sci. Rep. 5 1–11Google Scholar
  14. Harrell FEJ 2012 Hmisc: Harrell Miscellaneous. R package version 3.9.3Google Scholar
  15. He X and Zhang J 2006 Why do hubs tend to be essential in protein networks? PLoS Genet 2.  https://doi.org/10.1371/journal.pgen.0020088 CrossRefGoogle Scholar
  16. Holm PS, Bergmann S, Jurchott K, Lage H, Brand K, Ladhoff A and Royer HD 2002 DNA: Replication repair and recombination: YB-1 relocates to the nucleus in adenovirus-infected cells and facilitates viral replication by inducing E2 gene expression through the E2 late promoter YB-1 relocates to the nucleus in adenovirus-infected cell. J. Biol. Chem. 277 10427–10434CrossRefGoogle Scholar
  17. Homer C, Knight DA, Hananeia L, Sheard P, Risk J, Lasham A and Braithwaite AW 2005 Y-box factor YB1 controls p53 apoptotic function. Oncogene 24 8314–8325CrossRefGoogle Scholar
  18. Hosseini H, Obradović MM, Hoffmann M, Harper KL, Sosa MS, Klein MW and Kelin CA 2016 Early dissemination seeds metastasis in breast cancer. Nat. Publ. Gr. 540 552–558CrossRefGoogle Scholar
  19. Hunter DJ 2005 Gene–environment interactions in human diseases. Nat. Rev. Genet. 6 287–298CrossRefGoogle Scholar
  20. Ise T, Nagatani G, Imamura T, Kato K, Takano H, Nomoto M and Kohno K 1999 Transcription factor Y-box binding protein 1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen 1. Cancer 59 342–346Google Scholar
  21. Jeong H, Mason S and Barabasi AL 2001 Lethality and centrality in protein networks. Nature 411 41–42CrossRefGoogle Scholar
  22. Kalra J, Sutherland BW, Stratford L, Dragowska W, Gelmon KA, Dedhar S and Bally MB 2010 Suppression of Her2/neu expression through ILK inhibition is regulated by a pathway involving TWIST and YB-1. Oncogene 29 6343–6356CrossRefGoogle Scholar
  23. Kohno K, Izumi H, Uchiumi T, Ashizuka M and Kuwano M 2003 The pleiotropic functions of the Y-box-binding protein, YB-1. BioEssays 25 691–698CrossRefGoogle Scholar
  24. Kuwano M, Uchiumi T, Hayakawa H, Ono M, Wada M, Izumi H and Kohno K 2003 The basic and clinical implications of ABC transporter, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies. Cancer Sci. 94 9–14CrossRefGoogle Scholar
  25. Kuwano M, Oda Y, Izumi H, Yang S, Uchiumi T, Iwamoto Y and Kohno K 2004 The role of nuclear Y-box binding protein 1 as a global marker in drug resistance. Mol. Cancer Ther. 3 1485–1492PubMedGoogle Scholar
  26. Lasham A, Lindridge E, Rudert F, Onrust R, Watson J, Lasham A and Rudert F 2000 Regulation of the human fas promoter by YB-1, pura and AP-1 transcription factors. Gene 252 1–13CrossRefGoogle Scholar
  27. Li B and Dewey CN 2011 RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinf. 12 323CrossRefGoogle Scholar
  28. Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P and Mesirov JP 2011 Molecular signatures database (MSigDB) 3.0. Bioinformatics 27 1739–1740CrossRefGoogle Scholar
  29. Love MI, Huber W and Anders S 2014 Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15 550CrossRefGoogle Scholar
  30. Maere S, Heymans K and Kuiper M 2005 BiNGO: a cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21 3448–3449CrossRefGoogle Scholar
  31. Makino Y, Ohga T, Toh S, Koike K, Okumura K, Wada M and Kohno K 1996 Structural and functional analysis of the human Y-box binding protein (YB-1) gene promoter. Nucleic Acids Res. 24 1873–1878CrossRefGoogle Scholar
  32. Mao Y 2013 The role of nuclear β-catenin accumulation in the Twist2- induced ovarian cancer EMT. PLoS One 8 1–11CrossRefGoogle Scholar
  33. Matsumoto K and Bay B 2005 Significance of the Y-box proteins in human cancers. J. Mol. Genet. Med. 1 11–17CrossRefGoogle Scholar
  34. Merico D, Isserlin R, Stueker O, Emili A and Bader GD 2010 Enrichment map: a network-based method for gene-Set enrichment visualization and interpretation. PLoS One 5 e13984CrossRefGoogle Scholar
  35. Mitchell MF, Koulos JP and Wright TC 1997 Adenocarcinoma of the cervix expression and clinical significance of estrogen and progesterone receptors. Cancer 79 505–512CrossRefGoogle Scholar
  36. Newton R and Wernisch L 2015 Investigating inter-chromosomal regulatory relationships through a comprehensive meta-analysis of matched copy number and transcriptomics data sets. BMC Genom. 16 1–12CrossRefGoogle Scholar
  37. Okamoto T, Izumi H, Imamura T, Takano H, Ise T, Uchiumi T and Kuwano M 2000 Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression. Oncogene 19 6194–6202CrossRefGoogle Scholar
  38. Papers JBC, Doi M, Marenstein DR, Ocampo MTA, Chan MK, Altamirano A and Teebor GW 2001 Stimulation of human endonuclease III by Y Box-binding protein 1 (DNA-binding protein B). J. Biol. Chem. 276 21242–21249CrossRefGoogle Scholar
  39. Pellecchia A, Pescucci C, De Lorenzo E, Luceri C, Passaro N, Sica M and De Angioletti M 2012 Overexpression of ETV4 is oncogenic in prostate cells through promotion of both cell proliferation and epithelial to mesenchymal transition. Oncogenesis 1 1–11CrossRefGoogle Scholar
  40. Pinto P, Herna MA, Kiran R, Kalathur R, Machado RSR, Almeida D and Futschik ME 2014 UniHI 7: an enhanced database for retrieval and interactive analysis of human molecular interaction networks. Nucleic Acids Res. 42 408–414CrossRefGoogle Scholar
  41. R Development Core Team 2016 R: A Language and Environment for Statistical Computing. R Found. Stat. Comput. Vienna Austria, 1, ISBN 3-900051-07-0Google Scholar
  42. Raychaudhuri P and Park HJ 2011 Foxm1: a master regulator of tumor metastasis. Cancer Res. 71 4329–4333CrossRefGoogle Scholar
  43. Raza K and Jaiswal R 2013 Reconstruction and analysis of cancer – specific gene regulatory networks from gene expression profile. Int. J. Bioinf. Biosci. 3 25–34Google Scholar
  44. Ruzanov PV, Evdokimova VM, Korneeva NL, Hershey JWB and Ovchinnikov LP 1999 Interaction of the universal mRNA-binding protein, p50, with actin: a possible link between mRNA and microfilaments. J. Cell Sci. 3496 3487–3496Google Scholar
  45. Segal E, Friedman N, Koller D and Regev A 2004 A module map showing conditional activity of expression modules in cancer. Nat. Genet. 36 1090–1098CrossRefGoogle Scholar
  46. Shannon P, Markiel A, Ozier O, Balinga NS, Wang JT, Ramage D and Ideker T 2003 Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13 2498–2504CrossRefGoogle Scholar
  47. Shibahara K, Uchiumi T, Fukuda T, Kura S, Tominaga Y, Maehara Y and Kuwano M 2004 Targeted disruption of one allele of the Y-box binding protein-1 (YB-1) gene in mouse embryonic stem cells and increased sensitivity to cisplatin and mitomycin C. Cancer Sci. 95 348–353CrossRefGoogle Scholar
  48. Shibao K, Takano H, Nakayama Y, Okazaki K, Nagata N, Izumi H and Itoh H 1999 Enhanced coexpression of YB-1 and DNA topoisomerase II alpha genes in human colorectal carcinomas. Int. J. Cancer 83 732–737CrossRefGoogle Scholar
  49. Shiota M, Izumi H, Onitsuka T, Miyamoto N, Kashiwagi E, Kidani A and Kohno K 2008 Twist promotes tumor cell growth through YB-1 expression. Cancer Res. 68 98–105CrossRefGoogle Scholar
  50. Shiota M, Song Y, Yokomizo A, Kiyoshima K, Tada Y, Uchino H and Naito S 2010 Foxo3a suppression of urothelial cancer invasiveness through twist1, Y-box-binding protein 1, and E-cadherin regulation. Clin. Cancer Res. 16 5654–5663CrossRefGoogle Scholar
  51. Stratford AL, Fry CJ, Desilets C, Davies AH, Cho YY, Li Y and Dunn SE 2008 Y-box binding protein-1 serine 102 is a downstream target of p90 ribosomal S6 kinase in basal-like breast cancer cells. Breast Cancer Res. 10 1–12CrossRefGoogle Scholar
  52. Subramanian A, Tamayo P, Mootha VK, Mukherjee S and Ebert BL 2005 Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. PNAS 102 15545–15550CrossRefGoogle Scholar
  53. Sun S, Cheng S, Zhu Y, Zhang P, Liu N, Xu T and Lv Y 2016 Identification of PRKDC (protein kinase, DNA-activated, catalytic polypeptide) as an essential gene for colorectal cancer (CRCs) cells. Gene 584 90–96CrossRefGoogle Scholar
  54. Sutherland BW, Kucab J, Wu J, Lee C, Cheang MC, Yorida E and Dunn SE 2005 Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells. Oncogene 24 4281–4292CrossRefGoogle Scholar
  55. Tew KD, Manevich Y, Grek C, Xiong Y and Uys J 2012 The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer. Free Radic. Biol. Med. 51 299–313CrossRefGoogle Scholar
  56. Wang Z, Gerstein M and Snyder M 2009 RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10 57–63CrossRefGoogle Scholar
  57. Wang J, Xu B and Yuan P 2012 TOP2A amplification in breast cancer is a predictive marker of anthracycline-based neoadjuvant chemotherapy efficacy. Breast Cancer Res. Treat. 135 531–537CrossRefGoogle Scholar
  58. Wang J, Pol SU, Haberman AK, Wang C, Bara MAO and Sim FJ 2014 Transcription factor induction of human oligodendrocyte progenitor fate and differentiation. PNAS E2885–E2894.  https://doi.org/10.1073/pnas.1408295111 CrossRefGoogle Scholar
  59. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P and Morris Q 2010 The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 38 214–220CrossRefGoogle Scholar
  60. Watt FM, Estrach S and Ambler CA 2008 Epidermal notch signalling: differentiation, cancer and adhesion. Curr. Opin. Cell Biol. 20 171–179CrossRefGoogle Scholar
  61. Wei T and Wei MT 2016 Package ‘corrplot’. Statistician 56 316–324Google Scholar
  62. Wu J, Stratford AL, Astanehe A and Dunn SE 2007 YB-1 is a transcription/translation factor that orchestrates the oncogenome by hardwiring signal transduction to gene expression. Transl. Oncogenomics 2 49–65PubMedPubMedCentralGoogle Scholar
  63. Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-toh K and Kellis M 2005 Systematic discovery of regulatory motifs in human promoters and 3 UTRs by comparison of several mammals. Nature 434 338–345CrossRefGoogle Scholar
  64. Yuan ZY, Dai T, Wang S, Peng RJ, Li XH and Qin T 2014 Overexpression of ETV4 protein in triple-negative breast cancer is associated with a higher risk of distant metastasis. Onco. Targets Ther. 7 1733–1742CrossRefGoogle Scholar
  65. Zhou Z, Patel M, Ng N, Hsieh MH, Orth AP, Walker JR and Liu J 2014 Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening. BMC Bioinf. 14 1–13CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.Department of BiotechnologyMotilal Nehru National Institute of TechnologyAllahabadIndia
  2. 2.Center of BioinformaticsUniversity of AllahabadAllahabadIndia

Personalised recommendations