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Article

Construction and analysis of three networks of genes and microRNAs in adenocarcinoma

  • Authors:
    • Jiahui Ning
    • Xiaoxin Guo
    • Ning Wang
    • Luchen Xue
  • View Affiliations / Copyright

    Affiliations: Department of Computer Science and Technology, Jilin University, Changchun, Jilin 130012, P.R. China
  • Pages: 3243-3251
    |
    Published online on: September 3, 2015
       https://doi.org/10.3892/ol.2015.3676
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Abstract

Adenocarcinoma is one of the most serious diseases that threaten human health. Numerous studies have investigated adenocarcinoma and have obtained a considerable amount of data regarding genes and microRNA (miRNA) in adenocarcinoma. However, studies have only focused on one or a small number of genes and miRNAs, and the data is stored in a scattered form, making it challenging to summarize and assess the associations between the genes and miRNAs. In the present study, three networks of genes and miRNAs in adenocarcinoma were focused on. This enabled the construction of networks of elements involved in adenocarcinoma and the analysis of these networks, rather than only discussing one gene. Transcription factors (TFs), miRNAs, and target and host genes of miRNAs in adenocarcinoma, and the regulatory associations between these elements were identified in the present study. These elements and associations were then used to construct three networks, which consisted of the differentially‑expressed, associated and global networks. The similarities and differences between the three networks were compared and analyzed. In total, 3 notable TFs, consisting of TP53, phosphatase and tensin homolog and SMAD4, were identified in adenocarcinoma. These TFs were able to regulate the differentially‑expressed genes and the majority of the differentially‑expressed miRNAs. Certain important regulatory associations were also found in adenocarcinoma, in addition to self‑regulating associations between TFs and miRNAs. The upstream and downstream elements of the differentially‑expressed genes and miRNAs were recorded, which revealed the regulatory associations between genes and miRNAs. The present study clearly revealed components of the pathogenesis of adenocarcinoma and the regulatory associations between the elements in adenocarcinoma. The present study may aid the investigation of gene therapy in adenocarcinoma and provides a theoretical basis for studies of gene therapy methods as a treatment for adenocarcinoma.
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1 

Stewart BW and Wild CP: Chapter title. Oesophageal cancer. World Cancer Report. 2014.IARC Press. 2014.

2 

Narasimhan P, Hitti IF, Awan A, Desai M, Kanzer BF and McDonald E: Unusual presentations of prostatic adenocarcinoma: Lymph node metastasis. Hosp Physician. 38:43–48. 2002.

3 

Shalgi R, Lieber D, Oren M and Pilpel Y: Global and local architecture of the mammalian microRNA-transcription factor regulatory network. PLoS Comput Biol. 3:e1312007. View Article : Google Scholar : PubMed/NCBI

4 

O'Donnell KA, Wentzel EA, Zeller KI, Dang CV and Mendell JT: C-Myc-regulated microRNAs modulate E2F1 expression. Nature. 435:839–843. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Rodriguez A, Griffiths-Jones S, Ashurst JL and Bradley A: Identification of Mammalian microRNA host genes and transcription units. Genome Res. 14:1902–1910. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Baskerville S and Bartel DP: Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 11:241–247. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Cao G, Huang B, Liu Z, et al: Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways. Biochem Biophys Res Commun. 396:978–982. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Tran DH, Satou K, Ho TB and Pham TH: Computational discovery of miR-TF regulatory modules in human genome. Bioinformation. 4:371–377. 2010. View Article : Google Scholar : PubMed/NCBI

9 

He L, He X, Lim LP, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Naeem H, Küffner R and Zimmer R: MIRTFnet: Analysis of miRNA regulated transcription factors. PLoS One. 6:e225192011. View Article : Google Scholar : PubMed/NCBI

11 

Hobert O: Gene regulation by transcription factors and microRNAs. Science. 319:1785–1786. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Li M, Li J, Ding X, He M and Cheng Y: microRNA and cancer. AAPS J. 12:309–317. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Wang J, Lu M, Qiu C and Cui Q: TransmiR: A transcription factor-microRNA regulation database. Nucleic Acids Res. 38:D119–D122. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Betel D, Wilson M, Gabow A, Marks DS and Sander C: The microRNA.org resource: Targets and expression. Nucleic Acids Res. 36:D149–D153. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Papadopoulos GL, Reczko M, Simossis VA, et al: The database of experimentally supported targets: A functional update of TarBase. Nucleic Acids Res. 37:D155–D158. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Hsu SD, Lin FM, Wu WY, et al: miRTarBase: A database curates experimentally validated microRNA-target interactions. Nucleic Acids Res. 39:D163–D169. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Kozomara A and Griffiths-Jones S: miRBase: Integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39:D152–D157. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Kanehisa M and Goto S: KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Bao J, Li Di, Wang L, et al: MicroRNA-449 and MicroRNA-34b/c function redundantly in murine testes by targeting E2F transcription factor-retinoblastoma protein (E2F-pRb) pathway. J Biol Chem. 287:21686–21698. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Revilla-Nuin B, Parilla P, Lozano JJ, et al: Predictive value of MicroRNAs in the progression of barrett esophagus to adenocarcinoma in a long-term follow-up study. Ann Surg. 257:886–893. 2013. View Article : Google Scholar : PubMed/NCBI

21 

National Center for Biotechnology Information: Single Nucleotide Polymorphism Database. simplewww.ncbi.nlm.gov/snpAccessed. May 10–2014

22 

Xue Y, Tayoun AN Abou, Abo KM, et al: MicroRNAs as diagnostic markers for pancreatic ductal adenocarcinoma and its precursor, pancreatic intraepithelial neoplasm. Cancer Genet. 206:217–221. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Kaduthanam S, Gade S, Meister M, et al: Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients. Lung Cancer. 80:223–227. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Que R, Ding G, Chen J and Cao L: Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma. World J Surg Oncol. 11:2192013. View Article : Google Scholar : PubMed/NCBI

25 

Cai B, An Y, Lv N, et al: miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2. Oncol Rep. 29:1769–1776. 2013.PubMed/NCBI

26 

Xu FX, Su YL, Zhang H, et al: Prognostic implications for high expression of MiR-25 in lung adenocarcinomas of female non-smokers. Asian Pac J Cancer Prev. 15:1197–1203. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Zhang R, Zheng S, Du Y, et al: Levels of HOXB7 and miR-337 in pancreatic ductal adenocarcinoma patients. Diagn Pathol. 9:612014. View Article : Google Scholar : PubMed/NCBI

28 

Kim J, Lim NJ, Jang SG, et al: miR-592 and miR-552 can distinguish between primary lung adenocarcinoma and colorectal cancer metastases in the lung. Anticancer Res. 34:2297–2302. 2014.PubMed/NCBI

29 

Wang W, Li F, Mao Y, et al: A miR-570 binding site polymorphism in the B7-H1 gene is associated with the risk of gastric adenocarcinoma. Hum Genet. 132:641–648. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Cortot AB, Younes M, Martel-Planche G, et al: Mutation of TP53 and alteration of p14(arf) expression in EGFR- and KRAS-mutated lung adenocarcinomas. Clin Lung Cancer. 15:124–130. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Heitzer E, Lax S, Lafer I, et al: Multiplex genetic cancer testing identifies pathogenic mutations in TP53 and CDH1 in a patient with bilateral breast and endometrial adenocarcinoma. BMC Med Genet. 14:1292013. View Article : Google Scholar : PubMed/NCBI

32 

Dulak AM, Stojanov P, Peng S, et al: Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 45:478–486. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Pérez-Mancera PA, Rust AG, van der Weyden L, et al: The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 486:266–270. 2012.PubMed/NCBI

34 

Orloff M, Peterson C, He X, et al: Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA. 306:410–419. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Safran M, Dalah I, Alexander J, Rosen N, Stein T Iny, Shmoish M, Nativ N, Bahir I, Doniger T, Krug H, et al: GeneCards Version 3: The human gene integrator. Database (Oxford). 2010:baq0202010. View Article : Google Scholar : PubMed/NCBI

36 

Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, Cline MS, Goldman M, Barber GP, Clawson H, Coelho A, et al: The UCSC genome browser database: Update 2011. Nucleic Acids Res. 39:D876–D882. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Zhao Z, Han C, Liu J, et al: GPC5, a tumor suppressor, is regulated by miR620 in lung adenocarcinoma. Mol Med Rep. 9:2540–2546. 2014.PubMed/NCBI

38 

Chen W, Qin L, Wang S, et al: CPSF4 activates telomerase reverse transcriptase and predicts poor prognosis in human lung adenocarcinomas. Mol Oncol. 8:704–716. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Allo G, Bandarchi B, Yanagawa N, et al: Epidermal growth factor receptor mutation-specific immunohistochemical antibodies in lung adenocarcinoma. Histopathology. 64:826–839. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Sekine S, Ogawa R, Oshiro T, et al: Frequent lack of GNAS mutations in colorectal adenocarcinoma associated with GNAS-mutated villous adenoma. Genes Chromosomes Cancer. 53:366–372. 2014. View Article : Google Scholar : PubMed/NCBI

41 

Chen YW, Hsiao PJ, Weng CC, et al: SMAD4 loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells. BMC Cancer. 14:1812014. View Article : Google Scholar : PubMed/NCBI

42 

Kim HR, Cho BC, Shim HS, et al: Prediction for response duration to epidermal growth factor receptor-tyrosine kinase inhibitors in EGFR mutated never smoker lung adenocarcinoma. Lung Cancer. 83:374–382. 2014. View Article : Google Scholar : PubMed/NCBI

43 

Luis-Ravelo D, Antón I, Zandueta C, et al: RHOB influences lung adenocarcinoma metastasis and resistance in a host-sensitive manner. Mol Oncol. 8:196–206. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Mehra R, Vats P, Kalyana-Sundaram, et al: Primary urethral clear-cell adenocarcinoma: Comprehensive analysis by surgical pathology, cytopathology, and next-generation sequencing. Am J Pathol. 184:584–591. 2014. View Article : Google Scholar : PubMed/NCBI

45 

Rondini EA, Fang H, Runge-Morris M and Kocarek TA: Regulation of human cytosolic sulfotransferases 1C2 and 1C3 by nuclear signaling pathways in LS180 colorectal adenocarcinoma cells. Drug Metab Dispos. 42:361–368. 2014. View Article : Google Scholar : PubMed/NCBI

46 

Davison JM, Ellis ST, Foxwell TJ, et al: MUC2 expression is an adverse prognostic factor in superficial gastroesophageal adenocarcinomas. Hum Pathol. 45:540–548. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Priolli DG, Abrantes AM, Neves S, et al: Microenvironment influence on human colon adenocarcinoma phenotypes and matrix metalloproteinase-2, p53 and β-catenin tumor expressions from identical monoclonal cell tumor in the orthotopic model in athymic nude rats. Scand J Gastroenterol. 49:309–316. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ning J, Guo X, Wang N and Xue L: Construction and analysis of three networks of genes and microRNAs in adenocarcinoma. Oncol Lett 10: 3243-3251, 2015.
APA
Ning, J., Guo, X., Wang, N., & Xue, L. (2015). Construction and analysis of three networks of genes and microRNAs in adenocarcinoma. Oncology Letters, 10, 3243-3251. https://doi.org/10.3892/ol.2015.3676
MLA
Ning, J., Guo, X., Wang, N., Xue, L."Construction and analysis of three networks of genes and microRNAs in adenocarcinoma". Oncology Letters 10.5 (2015): 3243-3251.
Chicago
Ning, J., Guo, X., Wang, N., Xue, L."Construction and analysis of three networks of genes and microRNAs in adenocarcinoma". Oncology Letters 10, no. 5 (2015): 3243-3251. https://doi.org/10.3892/ol.2015.3676
Copy and paste a formatted citation
x
Spandidos Publications style
Ning J, Guo X, Wang N and Xue L: Construction and analysis of three networks of genes and microRNAs in adenocarcinoma. Oncol Lett 10: 3243-3251, 2015.
APA
Ning, J., Guo, X., Wang, N., & Xue, L. (2015). Construction and analysis of three networks of genes and microRNAs in adenocarcinoma. Oncology Letters, 10, 3243-3251. https://doi.org/10.3892/ol.2015.3676
MLA
Ning, J., Guo, X., Wang, N., Xue, L."Construction and analysis of three networks of genes and microRNAs in adenocarcinoma". Oncology Letters 10.5 (2015): 3243-3251.
Chicago
Ning, J., Guo, X., Wang, N., Xue, L."Construction and analysis of three networks of genes and microRNAs in adenocarcinoma". Oncology Letters 10, no. 5 (2015): 3243-3251. https://doi.org/10.3892/ol.2015.3676
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