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Current Genomics

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ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

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Research Article

Comprehensive Analysis of the mRNA-lncRNA Co-expression Profile and ceRNA Networks Patterns in Chronic Hepatitis B

Author(s): Wenbiao Chen, Chenhong Lin, Lan Gong, Jianing Chen, Yan liang, Ping Zeng and Hongyan Diao*

Volume 20, Issue 4, 2019

Page: [231 - 245] Pages: 15

DOI: 10.2174/1389202920666190820122126

Price: $65

Abstract

Background: Long non-coding RNAs (lncRNAs) are emerging as important regulators in the modulation of virus infection by targeting mRNA transcription. However, their roles in chronic hepatitis B (CHB) remain to be elucidated.

Objective: The study aimed to explore the lncRNAs and mRNA expression profiles in CHB and asymptomatic HBsAg carriers (ASC) and construct mRNA-lncRNA co-expression profile and ceRNA networks to identify the potential targets of diagnosis and treatment in CHB.

Methods: We determined the expression profiles of lncRNAs and mRNAs in CHB and ASC using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore their function. We also constructed coexpression, cis-regulatory, and competing endogenous RNA (ceRNA) networks with bioinformatics methods.

Results: We identified 1634 mRNAs and 5550 lncRNAs that were differentially expressed between CHB and ASC. Significantly enriched GO terms and pathways were identified, many of which were linked to immune processes and inflammatory responses. Co-expression analysis showed 1196 relationships between the top 20 up/downregulated lncRNAs and mRNA, especially 213 lncRNAs interacted with ZFP57. The ZFP57-specific ceRNA network covered 3 lncRNAs, 5 miRNAs, and 17 edges. Cis-correlation analysis showed that lncRNA T039096 was paired with the most differentially expressed gene, ZFP57. Moreover, by expending the clinical samples size, the qRT-PCR results showed that the expression of ZFP57 and T039096 increased in CHB compared to ASC.

Conclusion: Our study provides insights into the roles of mRNA and lncRNA networks in CHB, highlighting potential applications of lncRNA-T039096 and mRNA-ZFP57 for diagnosis and treatment.

Keywords: lncRNA, mRNA, chronic hepatitis B, HBV, co-expression, ceRNA.

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[1]
Ren, H. The experience of management of chronic hepatitis B in China. J. Viral Hepat., 2017, 24(Suppl. 1), 4-5.
[http://dx.doi.org/10.1111/jvh.12793] [PMID: 29082643]
[2]
Soriano, V.; Young, B.; Reau, N. Report from the International Conference on Viral Hepatitis - 2017. AIDS Rev., 2018, 20(1), 58-70.
[http://dx.doi.org/10.24875/AIDSRev.M17000012] [PMID: 29369303]
[3]
Pungpapong, S.; Kim, W.R.; Poterucha, J.J. Natural history of hepatitis B virus infection: An update for clinicians. Mayo Clin. Proc., 2007, 82(8), 967-975.
[http://dx.doi.org/10.4065/82.8.967] [PMID: 17673066]
[4]
Busch, K.; Thimme, R. Natural history of chronic hepatitis B virus infection. Med. Microbiol. Immunol. (Berl.), 2015, 204(1), 5-10.
[http://dx.doi.org/10.1007/s00430-014-0369-7] [PMID: 25540037]
[5]
Romeo, R.; Petruzziello, A.; Pecheur, E.I.; Facchetti, F.; Perbellini, R.; Galmozzi, E.; Khan, N.U.; Di Capua, L.; Sabatino, R.; Botti, G.; Loquercio, G. Hepatitis delta virus and hepatocellular carcinoma: An update. Epidemiol. Infect., 2018, 146(13), 1612-1618.
[http://dx.doi.org/10.1017/S0950268818001942] [PMID: 29991359]
[6]
Sagnelli, E.; Felaco, F.M.; Rapicetta, M.; Stroffolini, T.; Petruzziello, A.; Annella, T.; Chionne, P.; Pasquale, G.; Filippini, P.; Peinetti, P. Interaction between HDV and HBV infection in HBsAg-chronic carriers. Infection, 1991, 19(3), 155-158.
[7]
Stroffolini, T.; Sagnelli, E.; Rapicetta, M.; Felaco, F.M.; Filippini, P.; Annella, T.; Petruzziello, A.; Chionne, P.; Sarrecchia, B.; Piccinino, F. Hepatitis B virus DNA in chronic HBsAg carriers: Correlation with HBeAg/anti-HBe status, anti-HD and liver histology. Hepatogastroenterology, 1992, 39(1), 62-65.
[8]
You, C.R.; Lee, S.W.; Jang, J.W.; Yoon, S.K. Update on hepatitis B virus infection. World J. Gastroenterol., 2014, 20(37), 13293-13305.
[http://dx.doi.org/10.3748/wjg.v20.i37.13293] [PMID: 25309066]
[9]
Yu, R.; Fan, R.; Hou, J. Chronic hepatitis B virus infection: Epidemiology, prevention, and treatment in China. Front. Med., 2014, 8(2), 135-144.
[http://dx.doi.org/10.1007/s11684-014-0331-5] [PMID: 24810645]
[10]
Alexander, R.P.; Fang, G.; Rozowsky, J.; Snyder, M.; Gerstein, M.B. Annotating non-coding regions of the genome. Nat. Rev. Genet., 2010, 11(8), 559-571.
[http://dx.doi.org/10.1038/nrg2814] [PMID: 20628352]
[11]
Ponting, C.P.; Oliver, P.L.; Reik, W. Evolution and functions of long noncoding RNAs. Cell, 2009, 136(4), 629-641.
[http://dx.doi.org/10.1016/j.cell.2009.02.006] [PMID: 19239885]
[12]
Ouyang, J.; Hu, J.; Chen, J.L. lncRNAs regulate the innate immune response to viral infection. Wiley Interdiscip. Rev. RNA, 2016, 7(1), 129-143.
[http://dx.doi.org/10.1002/wrna.1321] [PMID: 26667656]
[13]
Fortes, P.; Morris, K.V. Long noncoding RNAs in viral infections. Virus Res., 2016, 212, 1-11.
[http://dx.doi.org/10.1016/j.virusres.2015.10.002] [PMID: 26454188]
[14]
Salmena, L.; Poliseno, L.; Tay, Y.; Kats, L.; Pandolfi, P.P. A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language? Cell, 2011, 146(3), 353-358.
[http://dx.doi.org/10.1016/j.cell.2011.07.014] [PMID: 21802130]
[15]
Tay, Y.; Rinn, J.; Pandolfi, P.P. The multilayered complexity of ceRNA crosstalk and competition. Nature, 2014, 505(7483), 344-352.
[http://dx.doi.org/10.1038/nature12986] [PMID: 24429633]
[16]
Karreth, F.A.; Pandolfi, P.P. ceRNA cross-talk in cancer: When ce-bling rivalries go awry. Cancer Discov., 2013, 3(10), 1113-1121.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0202] [PMID: 24072616]
[17]
Li, L.J.; Zhao, W.; Tao, S.S.; Leng, R.X.; Fan, Y.G.; Pan, H.F.; Ye, D.Q. Competitive endogenous RNA network: Potential implication for systemic lupus erythematosus. Expert Opin. Ther. Targets, 2017, 21(6), 639-648.
[http://dx.doi.org/10.1080/14728222.2017.1319938] [PMID: 28406715]
[18]
Lai, K.; Jia, S.; Yu, S.; Luo, J.; He, Y. Genome-wide analysis of aberrantly expressed lncRNAs and miRNAs with associated co-expression and ceRNA networks in β-thalassemia and hereditary persistence of fetal hemoglobin. Oncotarget, 2017, 8(30), 49931-49943.
[http://dx.doi.org/10.18632/oncotarget.18263] [PMID: 28624809]
[19]
Lü, M.H.; Tang, B.; Zeng, S.; Hu, C.J.; Xie, R.; Wu, Y.Y.; Wang, S.M.; He, F.T.; Yang, S.M. Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene, 2016, 35(27), 3524-3534.
[http://dx.doi.org/10.1038/onc.2015.413] [PMID: 26549025]
[20]
Jiang, H.; Ma, R.; Zou, S.; Wang, Y.; Li, Z.; Li, W. Reconstruction and analysis of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in rheumatoid arthritis. Mol. Biosyst., 2017, 13(6), 1182-1192.
[http://dx.doi.org/10.1039/C7MB00094D] [PMID: 28470264]
[21]
Zhang, S.; Zhu, D.; Li, H.; Feng, C.; Zhang, W. Characterization of circRNA-associated-ceRNA networks in a senescence-accelerated mouse prone 8 brain. Molecular therapy. J. Am. Soc. Gene Ther, 2017, 25(9), 2053-2061.
[22]
Terrault, N.A.; Bzowej, N.H.; Chang, K.M.; Hwang, J.P.; Jonas, M.M.; Murad, M.H. AASLD guidelines for treatment of chronic hepatitis B. Hepatology, 2016, 63(1), 261-283.
[http://dx.doi.org/10.1002/hep.28156] [PMID: 26566064]
[23]
Huntley, R.P.; Harris, M.A.; Alam-Faruque, Y.; Blake, J.A.; Carbon, S.; Dietze, H.; Dimmer, E.C.; Foulger, R.E.; Hill, D.P.; Khodiyar, V.K.; Lock, A.; Lomax, J.; Lovering, R.C.; Mutowo-Meullenet, P.; Sawford, T.; Van Auken, K.; Wood, V.; Mungall, C.J. A method for increasing expressivity of Gene Ontology annotations using a compositional approach. BMC Bioinformatics, 2014, 15(1), 155.
[http://dx.doi.org/10.1186/1471-2105-15-155] [PMID: 24885854]
[24]
Kanehisa, M.; Goto, S.; Sato, Y.; Kawashima, M.; Furumichi, M.; Tanabe, M. Data, information, knowledge and principle: Back to metabolism in KEGG. Nucleic Acids Res., 2014, 42(Database issue), D199-D205.
[http://dx.doi.org/10.1093/nar/gkt1076] [PMID: 24214961]
[25]
Kambara, H.; Niazi, F.; Kostadinova, L.; Moonka, D.K.; Siegel, C.T.; Post, A.B.; Carnero, E.; Barriocanal, M.; Fortes, P.; Anthony, D.D.; Valadkhan, S. Negative regulation of the interferon response by an interferon-induced long non-coding RNA. Nucleic Acids Res., 2014, 42(16), 10668-10680.
[http://dx.doi.org/10.1093/nar/gku713] [PMID: 25122750]
[26]
Moyo, B.; Nicholson, S.A.; Arbuthnot, P.B. The role of long non-coding RNAs in hepatitis B virus-related hepatocellular carcinoma. Virus Res., 2016, 212, 103-113.
[http://dx.doi.org/10.1016/j.virusres.2015.07.025] [PMID: 26239319]
[27]
Huang, J.L.; Ren, T.Y.; Cao, S.W.; Zheng, S.H.; Hu, X.M.; Hu, Y.W.; Lin, L.; Chen, J.; Zheng, L.; Wang, Q. HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget, 2015, 6(32), 33791-33804.
[http://dx.doi.org/10.18632/oncotarget.5667] [PMID: 26393879]
[28]
Lu, J.; Xie, F.; Geng, L.; Shen, W.; Sui, C.; Yang, J. Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV. Tumour Biol., 2015, 36(5), 3231-3236.
[http://dx.doi.org/10.1007/s13277-014-2951-4] [PMID: 25501706]
[29]
Bertoletti, A.; Ferrari, C. Innate and adaptive immune responses in chronic hepatitis B virus infections: Towards restoration of immune control of viral infection. Gut, 2012, 61(12), 1754-1764.
[http://dx.doi.org/10.1136/gutjnl-2011-301073] [PMID: 22157327]
[30]
Bierne, H.; Hamon, M.; Cossart, P. Epigenetics and bacterial infections. Cold Spring Harb. Perspect. Med., 2012, 2(12)a010272
[http://dx.doi.org/10.1101/cshperspect.a010272] [PMID: 23209181]
[31]
Wu, Y.H.; Ai, X.; Liu, F.Y.; Liang, H.F.; Zhang, B.X.; Chen, X.P. c-Jun N-terminal kinase inhibitor favors transforming growth factor-β to antagonize hepatitis B virus X protein-induced cell growth promotion in hepatocellular carcinoma. Mol. Med. Rep., 2016, 13(2), 1345-1352.
[http://dx.doi.org/10.3892/mmr.2015.4644] [PMID: 26648552]
[32]
Li, L.; Lei, Q.S.; Kong, L.N.; Zhang, S.J.; Qin, B. Gene expression profile after knockdown of USP18 in Hepg2.2.15 cells. J. Med. Virol., 2017, 89(11), 1920-1930.
[http://dx.doi.org/10.1002/jmv.24819] [PMID: 28369997]
[33]
Ulitsky, I. Interactions between short and long noncoding RNAs. FEBS Lett., 2018, 592(17), 2874-2883.
[http://dx.doi.org/10.1002/1873-3468.13085] [PMID: 29749606]
[34]
Fan, H.; Lv, P.; Mu, T.; Zhao, X.; Liu, Y.; Feng, Y.; Lv, J.; Liu, M.; Tang, H. LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells. Cancer Lett., 2018, 429, 89-99.
[http://dx.doi.org/10.1016/j.canlet.2018.05.010] [PMID: 29753758]
[35]
Hou, X.; Liang, Y.; Chen, J.; Wei, Y.; Zeng, P.; Wang, L.; Lu, C.; Diao, H. Expression profiling of cellular MicroRNA in asymptomatic HBsAg carriers and chronic hepatitis B patients. BioMed Res. Int., 2017.20176484835
[http://dx.doi.org/10.1155/2017/6484835] [PMID: 28913356]

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