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Molecular Biology Reports

, Volume 41, Issue 5, pp 2875–2883 | Cite as

RETRACTED ARTICLE: Construction of pancreatic cancer double-factor regulatory network based on chip data on the transcriptional level

  • Li-Li Zhao
  • Tong Zhang
  • Bing-Rong Liu
  • Tie-Fu Liu
  • Na Tao
  • Li-Wei Zhuang
Article

Abstract

Transcription factor (TF) and microRNA (miRNA) have been discovered playing crucial roles in cancer development. However, the effect of TFs and miRNAs in pancreatic cancer pathogenesis remains vague. We attempted to reveal the possible mechanism of pancreatic cancer based on transcription level. Using GSE16515 datasets downloaded from gene expression omnibus database, we first identified the differentially expressed genes (DEGs) in pancreatic cancer by the limma package in R. Then the DEGs were mapped into DAVID to conduct the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. TFs and miRNAs that DEGs significantly enriched were identified by Fisher’s test, and then the pancreatic cancer double-factor regulatory network was constructed. In our study, total 1117 DEGs were identified and they significantly enriched in 4 KEGG pathways. A double-factor regulatory network was established, including 29 DEGs, 24 TFs, 25 miRNAs. In the network, LAMC2, BRIP1 and miR155 were identified which may be involved in pancreatic cancer development. In conclusion, the double-factor regulatory network was found to play an important role in pancreatic cancer progression and our results shed new light on the molecular mechanism of pancreatic cancer.

Keywords

Pancreatic cancer Transcription factor (TF) MicroRNA (miRNA) Differentially expressed genes (DEGs) 

Notes

Acknowledgments

This work was supported by the Fund of the Provincial Health Department of Heilongjiang Province (No. 2011-171), and we wish to express our warm thanks to Fenghe (Shanghai) Information Technology Co., Ltd. Their ideas and help gave a valuable added dimension to our research.

References

  1. 1.
    Ekbom A, Mclaughlin JK, Nyren O (1993) Pancreatitis and the risk of pancreatic cancer. N Engl J Med 329:1502–1503CrossRefPubMedGoogle Scholar
  2. 2.
    Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, Dimagno EP, Andren-Sandberg A, Domellof L (1993) Pancreatitis and the risk of pancreatic cancer. N Engl J Med 328:1433–1437CrossRefPubMedGoogle Scholar
  3. 3.
    Edwards LE and John Pojeta J, Fossils, Rocks, and Time, U.S.D.o.t. Interior, Editor. 1997, U.S. Geological SurveyGoogle Scholar
  4. 4.
    Wu SF, Qian WY, Zhang JW, Yang YB, Liu Y, Dong Y, Zhang ZB, Zhu YP, Feng YJ (2012) Network motifs in the transcriptional regulation network of cervical carcinoma cells respond to EGF. Arch Gynecol Obstet 287(4):771–777CrossRefPubMedGoogle Scholar
  5. 5.
    Higareda-Almaraz J, Enríquez-Gasca M, Hernández-Ortiz M, Resendis-Antonio O, Encarnación-Guevara S (2011) Proteomic patterns of cervical cancer cell lines, a network perspective. BMC Syst Biol 5:96PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Ying S-Y, Chang DC, Lin S-L (2008) The microRNA (miRNA): overview of the RNA genes that modulate gene function. Mol Biotechnol 38:257–268CrossRefPubMedGoogle Scholar
  7. 7.
    Schöniger C, Arenz C (2013) Perspectives in targeting miRNA function. Bioorg Med Chem 21(20):6115–6118CrossRefPubMedGoogle Scholar
  8. 8.
    Pai P, Rachagani S, Are C, Batra S (2013) Prospects of miRNA-based therapy for pancreatic cancer. Curr Drug Targets 14(10):1101–1109PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Xue Y, Abou Tayoun AN, Abo KM, Pipas JM, Gordon SR, Gardner TB, Barth RJ Jr, Suriawinata AA, Tsongalis GJ (2013) MicroRNAs as diagnostic markers for pancreatic ductal adenocarcinoma and its precursor, pancreatic intraepithelial neoplasm. Cancer Genet 206(6):217–221CrossRefPubMedGoogle Scholar
  10. 10.
    Kim JH, Lee JY, Lee KT, Lee JK, Lee KH, Jang K-T, Heo JS, Choi SH, Rhee JC (2010) RGS16 and FosB underexpressed in pancreatic cancer with lymph node metastasis promote tumor progression. Tumor Biol 31:541–548CrossRefGoogle Scholar
  11. 11.
    Fu B, Luo M, Lakkur S, Lucito R, Iacobuzio-Donahue CA (2008) Frequent genomic copy number gain and overexpression of GATA-6 in pancreatic carcinoma. Cancer Biol Ther 7:1593–1601CrossRefPubMedGoogle Scholar
  12. 12.
    Pei H, Li L, Fridley BL, Jenkins GD, Kalari KR, Lingle W, Petersen G, Lou Z, Wang L (2009) FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell 16:259–266PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Lee K-H, Lotterman C, Karikari C, Omura N, Feldmann G, Habbe N, Goggins MG, Mendell JT, Maitra A (2009) Epigenetic silencing of microRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer. Pancreatology 9:293–301PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:P3CrossRefPubMedGoogle Scholar
  15. 15.
    Harris M, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, Eilbeck K, Lewis S, Marshall B, Mungall C (2004) The gene ontology (GO) database and informatics resource. Nucleic Acids Res 32:D258–D261CrossRefPubMedGoogle Scholar
  16. 16.
    Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu Y, Roskin KM, Schwartz M, Sugnet CW, Thomas DJ (2003) The UCSC genome browser database. Nucleic Acids Res 31:51–54PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Papadopoulos GL, Reczko M, Simossis VA, Sethupathy P, Hatzigeorgiou AG (2009) The database of experimentally supported targets: a functional update of TarBase. Nucleic Acids Res 37:D155–D158PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Da Wei Huang BTS, Lempicki RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57CrossRefGoogle Scholar
  20. 20.
    Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1–13PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Lee H-J, Jang M, Kim H, Kwak W, Park W, Hwang JY, Lee C-K, Jang GW, Park MN, Kim H-C (2013) Comparative transcriptome analysis of adipose tissues reveals that ECM-receptor interaction is involved in the depot-specific adipogenesis in cattle. PLoS One 8:e66267PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Ding D, Lou X, Hua D, Yu W, Li L, Wang J, Gao F, Zhao N, Ren G, Li L (2012) Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. PLoS Genet 8:e1003065PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Krupp M, Maass T, Marquardt J, Staib F, Bauer T, König R, Biesterfeld S, Galle P, Tresch A, Teufel A (2011) The functional cancer map: a systems-level synopsis of genetic deregulation in cancer. BMC Med Genomics 4:53PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Li Z, Gou J, Xu J (2013) Down-regulation of focal adhesion signaling in response to cyclophilin A knockdown in human endometrial cancer cells, implicated by cDNA microarray analysis. Gynecol Oncol 131(1):191–197CrossRefPubMedGoogle Scholar
  25. 25.
    Liao Q, Kleeff J, Xiao Y, Di Cesare P, Korc M, Zimmermann A, Büchler M, Friess H (2003) COMP is selectively up-regulated in degenerating acinar cells in chronic pancreatitis and in chronic-pancreatitis-like lesions in pancreatic cancer. Scand J Gastroenterol 38:207–215CrossRefPubMedGoogle Scholar
  26. 26.
    Zgheib NB, Xiong Y, Marchion DC, Bicaku E, Chon HS, Stickles XB, Sawah EA, Judson PL, Hakam A, Gonzalez-Bosquet J (2012) The O-glycan pathway is associated with in vitro sensitivity to gemcitabine and overall survival from ovarian cancer. Int J Oncol 41:179–188PubMedCentralGoogle Scholar
  27. 27.
    Kwon O-H, Park J-L, Kim M, Kim J-H, Lee H-C, Kim H-J, Noh S-M, Song K-S, Yoo H-S, Paik S-G (2011) Aberrant up-regulation of LAMB3 and LAMC2 by promoter demethylation in gastric cancer. Biochem Biophys Res Commun 406:539–545CrossRefPubMedGoogle Scholar
  28. 28.
    Kosanam H, Prassas I, Chrystoja CC, Soleas I, Chan A, Dimitromanolakis A, Blasutig IM, Rückert F, Gruetzmann R, Pilarsky C (2013) LAMC2: a promising new pancreatic cancer biomarker identified by proteomic analysis of pancreatic adenocarcinoma tissues. Mol Cell Proteomics 12(10):2820–2832PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Greither T, Grochola LF, Udelnow A, Lautenschläger C, Würl P, Taubert H (2010) Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 126:73–80CrossRefPubMedGoogle Scholar
  30. 30.
    De Nicolo A, Tancredi M, Lombardi G, Flemma CC, Barbuti S, Di Cristofano C, Sobhian B, Bevilacqua G, Drapkin R, Caligo MA (2008) A novel breast cancer-associated BRIP1 (FANCJ/BACH1) germ-line mutation impairs protein stability and function. Clin Cancer Res 14:4672–4680PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Thompson D, Easton DF (2002) Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94:1358–1365CrossRefPubMedGoogle Scholar
  32. 32.
    Detjen K, Farwig K, Welzel M, Wiedenmann B, Rosewicz S (2001) Interferon γ inhibits growth of human pancreatic carcinoma cells via caspase-1 dependent induction of apoptosis. Gut 49:251–262PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Bouker KB, Skaar TC, Riggins RB, Harburger DS, Fernandez DR, Zwart A, Wang A, Clarke R (2005) Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosis. Carcinogenesis 26:1527–1535CrossRefPubMedGoogle Scholar
  34. 34.
    Connett JM, Badri L, Giordano TJ, Connett WC, Doherty GM (2005) Interferon regulatory factor 1 (IRF-1) and IRF-2 expression in breast cancer tissue microarrays. J Interferon Cytokine Res 25:587–594CrossRefPubMedGoogle Scholar
  35. 35.
    Cho W (2007) OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer 6:60PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Li-Li Zhao
    • 1
  • Tong Zhang
    • 2
  • Bing-Rong Liu
    • 3
  • Tie-Fu Liu
    • 1
  • Na Tao
    • 1
  • Li-Wei Zhuang
    • 1
  1. 1.Department of GastroenterologyThe Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of CardiologyThe Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina
  3. 3.Department of GastroenterologyThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina

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