Bioinformatic analysis of miRNA–mRNA interaction associated with LMP2A gene in nasopharyngeal carcinoma
Abstract
Aim: The purpose of the study was to construct miRNA–mRNA network associated with LMP2A in nasopharyngeal carcinoma (NPC). Materials & methods: The dataset GSE53914, GSE12452 and GSE26596 were downloaded from Gene Expression Omnibus and differentially expressed genes (DEGs) identified by GEO2R. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed by ClusterProfiler R package. Protein–protein interaction network and mRNA–miRNA network associated with LMP2A were constructed. Hub genes were identified by Cytoscape. Results: The 135 DEGs associated with LMP2A were identified in NPC. Gene ontology function analysis showed DEGs were significantly enriched in cell–cell adhesion and NF-κB pathway. The hub genes were related to cell cycle. miRNA–mRNA network associated with LMP2A was constructed. Conclusion: The network may provide a way to explore the function of LMP2A in NPC by miRNA.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Detection of Epstein–Barr virus genome in nasopharyngeal carcinoma by in situ DNA hybridization. Intervirology 36(2), 91–98 (1993).
- 2. . Molecular diagnosis of Epstein–Barr virus-related diseases. J. Mol. Diagn. 3(1), 1–10 (2001).
- 3. . Epstein–Barr virus-associated epithelial and mesenchymal neoplasms. Hum. Pathol. 39(4), 473–483 (2008).
- 4. . Novel virally targeted therapies of EBV-associated tumors. Curr. Cancer Drug Targets 8(7), 591–596 (2008).
- 5. Epstein–Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. Int. J. Cancer 70(4), 375–382 (1997).
- 6. . EBV-positive primary pulmonary lymphoepithelioma-like carcinoma response to PD-L1 blockade. Clin. Lung Cancer
doi:10.1016/j.cllc.2018.12.015 (2018) (Epub ahead of print). - 7. Outlooks on Epstein–Barr virus associated gastric cancer. Cancer Treat. Rev. 66, 15–22 (2018).
- 8. . The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin. Cancer Biol. 22(2), 144–153 (2012).
- 9. S100A4 hypomethylation affects epithelial–mesenchymal transition partially induced by LMP2A in nasopharyngeal carcinoma. Mol. Carcinog.
doi:10.1002/mc.22389 (2015) (Epub ahead of print). - 10. EBV-encoded LMP2A promotes EMT in nasopharyngeal carcinoma via MTA1 and mTOR signaling induction. J. Virol.
doi:10.1128/jvi.01867-14 (2014) (Epub ahead of print). • LMP2A induced epithelial–mesenchymal transition through various signaling pathways. - 11. Epstein–Barr virus-encoded LMP2A induces an epithelial-mesenchymal transition and increases the number of side population stem-like cancer cells in nasopharyngeal carcinoma. PLoS Pathog. 6(6), e1000940 (2010).
- 12. . Diet and nasopharyngeal carcinoma. Prog. Clin. Biol. Res. 346, 93–105 (1990).
- 13. . The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol. Biomarkers Prev. 15(10), 1765–1777 (2006).
- 14. . Nasopharyngeal carcinoma. Orphanet J. Rare Dis. 1, 23 (2006).
- 15. . Update on the management and therapeutic monitoring of advanced nasopharyngeal cancer. Hematol. Oncol. Clin. North Am. 22(6), 1267–1278, x (2008).
- 16. . miRNA target enrichment analysis reveals directly active miRNAs in health and disease. Nucleic Acids Res. 41(3), e45 (2013).
- 17. Biweekly combination chemotherapy with paclitaxel and carboplatin for advanced non-small-cell lung cancer. J. Clin. Oncol. 22(14 Suppl.), 7335 (2004).
- 18. . Expression of adrenomedullin mRNA is altered with gestation and labour in human placenta and fetal membranes. Clin. Sci. 110(3), 337–342 (2006).
- 19. . Overexpressed miRNA-155 dysregulates intestinal epithelial apical junctional complex in severe acute pancreatitis. World J. Gastroenterol. 19(45), 8282–8291 (2013).
- 20. The effects of microRNA-98 inhibits cell proliferation and invasion by targeting STAT3 in nasopharyngeal carcinoma. Biomed. Pharmacother. 93, 869–878 (2017).
- 21. MicroRNA-19b-3p regulates nasopharyngeal carcinoma radiosensitivity by targeting TNFAIP3/NF-κB axis. J. Exp. Clin. Cancer Res. 35(1), 188 (2016).
- 22. MicroRNA-93 promotes cell growth and invasion in nasopharyngeal carcinoma by targeting disabled homolog-2. Cancer Lett. 363(2), 146–155 (2015).
- 23. NCBI GEO: archive for functional genomics data sets – update. Nucleic Acids Res. 41, D991–D995 (2013).
- 24. . miRWalk: an online resource for prediction of microRNA binding sites. PLoS ONE 13(10), e0206239 (2018).
- 25. . The signaling pathways of Epstein–Barr virus-encoded latent membrane protein 2A (LMP2A) in latency and cancer. Cell. Mol. Biol. Lett. 14(2), 222–247 (2009). •• The roles of LMP2A in the Epstein–Barr virus-associated latency state and various malignancies.
- 26. . Comprehensive profiling of functional Epstein–Barr virus miRNA expression in human cell lines. BMC Genomics 17, 644 (2016).
- 27. Downregulation of microRNA-200 in EBV-associated gastric carcinoma. Cancer Res. 70(11), 4719–4727 (2010). •• LMP2A played an important role in cancer process by regulating miR-200.
- 28. Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A. PLoS ONE 6(4), e19137 (2011).
- 29. . EBV LMP2A affects LMP1-mediated NF-κB signaling and survival of lymphoma cells by regulating TRAF2 expression. Blood 111(7), 3813–3820 (2008).
- 30. . Epstein–Barr virus and gastric carcinoma: virus–host interactions leading to carcinoma. Cancer Sci. 99(9), 1726–1733 (2008).
- 31. Induction of CCL5 by Epstein–Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma. Cancer Sci.
doi:10.1111/cas.13584 (2018) (Epub ahead of print). - 32. . JNK MAPK pathway regulates constitutive transcription of CCL5 by human NK cells through SP1. J. Immunol. 182(2), 1011–1020 (2009).
- 33. Induction of CCL5 by Epstein–Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma. Cancer Science 109(5), 1710–1722 (2018).
- 34. . Costimulatory molecules (CD80 and CD86) on Reed–Sternberg cells are associated with the proliferation of background T cells in Hodgkin’s disease. Pathol. Int. 48(1), 10–14 (1998).
- 35. Epstein–Barr virus latent membrane protein 2A (LMP2A)-mediated changes in Fas expression and Fas-dependent apoptosis: role of Lyn/Syk activation. Cell. Immunol. 297(2), 108–119 (2015).
- 36. . Inflammasome control of viral infection. Curr. Opin. Virol. 12, 38–46 (2015).
- 37. Epstein–Barr virus-encoded LMP2A regulates viral and cellular gene expression by modulation of the NF-κB transcription factor pathway. Proc. Natl Acad. Sci. USA 101(44), 15730–15735 (2004).