Gene expression analysis of potential genes and pathways involved in the pathogenic mechanisms of parvovirus B19 in human colorectal cancer

Zhang,Wei‑Ping; Yang,Hua; Chen,Hong; Zhu,Hai‑Rong; Lei,Quan; Song,Yun‑Hong; Dai,Zhong‑Ming; Sun,Jing‑Shan; Jiang,Li‑Li; Nie,Zhan‑Guo

doi:10.3892/ol.2014.2151

Gene expression analysis of potential genes and pathways involved in the pathogenic mechanisms of parvovirus B19 in human colorectal cancer

Authors:
- Wei‑Ping Zhang
- Hua Yang
- Hong Chen
- Hai‑Rong Zhu
- Quan Lei
- Yun‑Hong Song
- Zhong‑Ming Dai
- Jing‑Shan Sun
- Li‑Li Jiang
- Zhan‑Guo Nie
View Affiliations

Affiliations: Department of Gastroenterology and Hepatology, Urumqi Military General Hospital, Urumqi, Xinjiang 830000, P.R. China, Department of Outpatients, Urumqi Military General Hospital, Urumqi, Xinjiang 830000, P.R. China, Department of Blood Transfusion, Urumqi Military General Hospital, Urumqi, Xinjiang 830000, P.R. China, Department of Medical Administration, Urumqi Military General Hospital, Urumqi, Xinjiang 830000, P.R. China
Published online on: May 16, 2014 https://doi.org/10.3892/ol.2014.2151
Pages: 523-532

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In order to investigate the pathogenic mechanisms of parvovirus B19 in human colorectal cancer, plasmids containing the VP1 or VP2 viral capsid proteins or the NS1 non‑structural proteins of parvovirus B19 were constructed and transfected into primary human colorectal epithelial cells and LoVo cells. Differential gene expression was detected using a human genome expression array. Functional gene annotation analyses were performed using Database for Annotation, Visualization and Integrated Discovery v6.7 software. Gene ontology (GO) analyses revealed that VP1‑related functions included the immune response, immune system process, defense response and the response to stimulus, while NS1‑associated functions were found to include organelle fission, nuclear division, mitosis, the M‑phase of the mitotic cell cycle, the mitotic cell cycle, M‑phase, cell cycle phase, cell cycle process and cell division. Pathway expression analysis revealed that VP1‑associated pathways included cell adhesion molecules, antigen processing and presentation, cytokines and the inflammatory response. Moreover, NS1‑associated pathways included the cell cycle, pathways in cancer, colorectal cancer, the wnt signaling pathway and focal adhesion. Among the differential genes detected in the present study, 12 genes were found to participate in general cancer pathways and six genes were observed to participate in colorectal cancer pathways. NS1 is a key molecule in the pathogenic mechanism of parvovirus B19 in colorectal cancer. Several GO categories, pathways and genes were selected and may be the key targets through which parvovirus B19 participates in colorectal cancer pathogenesis.

View Figures

View References

1	Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011.
2	Pagano JS, Blaser M, Buendia MA, et al: Infectious agents and cancer: criteria for a causal relation. Semin Cancer Biol. 14:453–471. 2004.
3	Newcomb PA, Bush AC, Stoner GL, et al: No evidence of an association of JC virus and colon neoplasia. Cancer Epidemiol Biomarkers Prev. 13:662–666. 2004.
4	Ricciardiello L, Laghi L, Ramamirtham P, et al: JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology. 119:1228–1235. 2000.
5	Young NS and Brown KE: Parvovirus B19. N Engl J Med. 350:586–597. 2004.
6	Li Y, Wang J, Zhu G, et al: Detection of parvovirus B19 nucleic acids and expression of viral VP1/VP2 antigen in human colon carcinoma. Am J Gastroenterol. 102:1489–1498. 2007.
7	Kerr JR, Barah F, Cunniffe VS, et al: Association of acute parvovirus B19 infection with new onset of acute lymphoblastic and myeloblastic leukaemia. J Clin Pathol. 56:873–875. 2003.
8	Perreault N and Beaulieu JF: Use of the dissociating enzyme thermolysin to generate viable human normal intestinal epithelial cell cultures. Exp Cell Res. 224:354–364. 1996.
9	von Poblotzki A, Gigler A, Lang B, Wolf H and Modrow S: Antibodies to parvovirus B19 NS-1 protein in infected individuals. J Gen Virol. 76:519–527. 1995.
10	Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009.
11	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009.
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001.
13	Doerig C, Hirt B, Antonietti JP and Beard P: Nonstructural protein of parvoviruses B19 and minute virus of mice controls transcription. J Virol. 64:387–396. 1990.
14	Raab U, Beckenlehner K, Lowin T, et al: NS1 protein of parvovirus B19 interacts directly with DNA sequences of the p6 promoter and with the cellular transcription factors Sp1/Sp3. Virology. 293:86–93. 2002.
15	Momoeda M, Wong S, Kawase M, Young NS and Kajigaya S: A putative nucleoside triphosphate-binding domain in the nonstructural protein of B19 parvovirus is required for cytotoxicity. J Virol. 68:8443–8446. 1994.
16	Moffatt S, Yaegashi N, Tada K, Tanaka N and Sugamura K: Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid lineage cells. J Virol. 72:3018–3028. 1998.
17	Kajigaya S, Fujii H, Field A, et al: Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions. Proc Natl Acad Sci USA. 88:4646–4650. 1991.
18	Brown KE, Anderson SM and Young NS: Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science. 262:114–117. 1993.
19	Ozawa K and Young N: Characterization of capsid and noncapsid proteins of B19 parvovirus propagated in human erythroid bone marrow cell cultures. J Virol. 61:2627–2630. 1987.
20	Saikawa T, Anderson S, Momoeda M, Kajigaya S and Young NS: Neutralizing linear epitopes of B19 parvovirus cluster in the VP1 unique and VP1–VP2 junction regions. J Virol. 67:3004–3009. 1993.
21	Rosenfeld SJ, Yoshimoto K, Kajigaya S, et al: Unique region of the minor capsid protein of human parvovirus B19 is exposed on the virion surface. J Clin Invest. 89:2023–2029. 1992.
22	Kawase M, Momoeda M, Young NS and Kajigaya S: Most of the VP1 unique region of B19 parvovirus is on the capsid surface. Virology. 211:359–366. 1995.
23	Lu J, Zhi N, Wong S and Brown KE: Activation of synoviocytes by the secreted phospholipase A2 motif in the VP1-unique region of parvovirus B19 minor capsid protein. J Infect Dis. 193:582–590. 2006.
24	Zádori Z, Szelei J, Lacoste MC, et al: A viral phospholipase A2 is required for parvovirus infectivity. Dev Cell. 1:291–302. 2001.
25	Luo W and Astell CR: A novel protein encoded by small RNAs of parvovirus B19. Virology. 195:448–455. 1993.
26	St Amand J and Astell CR: Identification and characterization of a family of 11-kDa proteins encoded by the human parvovirus B19. Virology. 192:121–131. 1993.
27	St Amand J, Beard C, Humphries K and Astell CR: Analysis of splice junctions and in vitro and in vivo translation potential of the small, abundant B19 parvovirus RNAs. Virology. 183:133–142. 1991.
28	Fan MM, Tamburic L, Shippam-Brett C, Zagrodney DB and Astell CR: The small 11-kDa protein from B19 parvovirus binds growth factor receptor-binding protein 2 in vitro in a Src homology 3 domain/ligand-dependent manner. Virology. 291:285–291. 2001.
29	Moffatt S, Tanaka N, Tada K, et al: A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces activation of interleukin-6 gene expression. J Virol. 70:8485–8491. 1996.
30	Wan Z, Zhi N, Wong S, et al: Human parvovirus B19 causes cell cycle arrest of human erythroid progenitors via deregulation of the E2F family of transcription factors. J Clin Invest. 120:3530–3544. 2010.