Expression signature of microRNA‑155 in hepatitis C virus genotype 4 infection

Riad,Sarah  Ehab; El‑Ekiaby,Nada; Mekky,Radwa  Yehia; Ahmed,Rasha; Mohey El Din,Mohammad   Ahmed; El‑Sayed,Mohammad; Abouelkhair,Mahmoud   Mohammad; Salah,Ayman; Zekri,Abdel  Rahman; Esmat,Gamal; Abdelaziz,Ahmed  Ihab

doi:10.3892/br.2014.373

Expression signature of microRNA‑155 in hepatitis C virus genotype 4 infection

Authors:
- Sarah Ehab Riad
- Nada El‑Ekiaby
- Radwa Yehia Mekky
- Rasha Ahmed
- Mohammad Ahmed Mohey El Din
- Mohammad El‑Sayed
- Mahmoud Mohammad Abouelkhair
- Ayman Salah
- Abdel Rahman Zekri
- Gamal Esmat
- Ahmed Ihab Abdelaziz
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Affiliations: The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, German University in Cairo, New Cairo 11835, Egypt, Department of Endemic Medicine and Hepatology, Cairo University, Cairo 11562, Egypt, Department of Surgery, Cairo University, Cairo 11562, Egypt, Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11976, Egypt
Published online on: October 22, 2014 https://doi.org/10.3892/br.2014.373
Pages: 93-97

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Abstract

Hepatits C virus (HCV) genotype 4 (GT4) shows low treatment response rates and discrepancies when compared to other genotypes. However, the reason underlying these discrepancies remains unclear due to the limited number of studies on GT4. microRNA‑155 (miR‑155) is a noteworthy example of a discrepancy in GT4, as it was found to be upregulated in genotypes 1, 2 and 3 HCV infection, but downregulated in GT4‑HCV‑infected peripheral blood mononuclear cells (PBMCs). The present study aimed to investigate the expression of miR‑155 in PBMCs, serum and liver tissues of GT4‑HCV‑infected patients. miR‑155 expression was assessed using reverse transcription‑quantitative polymerase chain reaction in GT4‑HCV‑infected PBMCs, serum and liver tissues, as well as GT2‑ and GT4‑infected Huh7 cells, and compared to the healthy controls. There was no difference in miR‑155 expression observed between naïve GT4‑HCV patients and healthy controls in the PBMCs and serum. In HCV‑infected liver tissues, however, a significant downregulation was observed. The unique miR‑155 expression pattern during GT4 infection was confirmed in the infected Huh7 cell lines when compared to GT2 infection. Clinical data showed a positive correlation between liver transaminases and serum miR‑155 expression. In addition, serum miR‑155 expression was significantly lower in naïve non‑responders (NRs) than naïve sustained virological responders (SVRs), and in post‑treatment NRs compared to post‑treatment SVRs. In conclusion, miR‑155 was not only proven to be a genotype‑specific microRNA that is not induced during GT4‑HCV infection, but also a good prognostic factor and predictor of response to treatment enabling a non‑invasive differentiation between NRs and SVRs during GT4‑HCV infection.

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1	Lu M, Zhang Q, Deng M, Miao J, Guo Y, Gao W and Cui Q: An analysis of human microRNA and disease associations. PLoS One. 3:e34202008. View Article : Google Scholar : PubMed/NCBI
2	Wang P, Hou J, Lin L, et al: Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol. 185:6226–6233. 2010. View Article : Google Scholar : PubMed/NCBI
3	Zhang Y, Wei W, Cheng N, Wang K, Li B, Jiang X and Sun S: Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling. Hepatology. 56:1631–1640. 2012. View Article : Google Scholar : PubMed/NCBI
4	Su C, Hou Z, Zhang C, Tian Z and Zhang J: Ectopic expression of microRNA-155 enhances innate antiviral immunity against HBV infection in human hepatoma cells. Virol J. 8:3542011. View Article : Google Scholar : PubMed/NCBI
5	O'Connell RM, Taganov KD, Boldin MP, Cheng G and Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 104:1604–1609. 2007.PubMed/NCBI
6	Zhou H, Huang X, Cui H, et al: miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells. Blood. 116:5885–5894. 2010. View Article : Google Scholar
7	Ceppi M, Pereira PM, Dunand-Sauthier I, Barras E, Reith W, Santos MA and Pierre P: MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci USA. 106:2735–2740. 2009. View Article : Google Scholar : PubMed/NCBI
8	Haasch D, Chen YW, Reilly RM, et al: T cell activation induces a noncoding RNA transcript sensitive to inhibition by immunosuppressant drugs and encoded by the proto-oncogene, BIC. Cell Immunol. 217:78–86. 2002. View Article : Google Scholar : PubMed/NCBI
9	Thai TH, Calado DP, Casola S, et al: Regulation of the germinal center response by microRNA-155. Science. 316:604–608. 2007. View Article : Google Scholar : PubMed/NCBI
10	Bala S, Tilahun Y, Taha O, Alao H, Kodys K, Catalano D and Szabo G: Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection. J Transl Med. 10:1512012. View Article : Google Scholar : PubMed/NCBI
11	Kutty RK, Nagineni CN, Samuel W, Vijayasarathy C, Hooks JJ and Redmond TM: Inflammatory cytokines regulate microRNA-155 expression in human retinal pigment epithelial cells by activating JAK/STAT pathway. Biochem Biophys Res Commun. 402:390–395. 2010. View Article : Google Scholar : PubMed/NCBI
12	Linnstaedt SD, Gottwein E, Skalsky RL, Luftig MA and Cullen BR: Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. J Virol. 84:11670–11678. 2010. View Article : Google Scholar : PubMed/NCBI
13	Sidorkiewicz M, Grek M, Jozwiak B, Majda-Stanislawska E, Piekarska A and Bartkowiak J: Expression of microRNA-155 precursor in peripheral blood mononuclear cells from Hepatitis C patients after antiviral treatment. Acta Virol. 54:75–78. 2010. View Article : Google Scholar : PubMed/NCBI
14	Grek M, Piekarska A, Bartkowiak J, et al: Coordinated increase of miRNA-155 and miRNA-196b expression correlates with the detection of the antigenomic strand of hepatitis C virus in peripheral blood mononuclear cells. Int J Mol Med. 28:875–880. 2011.PubMed/NCBI
15	El-Ekiaby N, Hamdi N, Negm M, Ahmed R, Zekri AR, Esmat G and Abdelaziz AI: Repressed induction of interferon-related microRNAs miR-146a and miR-155 in peripheral blood mononuclear cells infected with HCV genotype 4. FEBS Open Bio. 2:179–186. 2012. View Article : Google Scholar : PubMed/NCBI
16	Guerra J, Garenne M, Mohamed MK and Fontanet A: HCV burden of infection in Egypt: results from a nationwide survey. J Viral Hepat. 19:560–567. 2012. View Article : Google Scholar : PubMed/NCBI
17	Stuyver L, Wyseur A, van Arnhem W, Hernandez F and Maertens G: Second-generation line probe assay for hepatitis C virus genotyping. J Clin Microbiol. 34:2259–2266. 1996.PubMed/NCBI
18	Liu X, Wang T, Wakita T and Yang W: Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology. 398:57–67. 2010. View Article : Google Scholar : PubMed/NCBI
19	Li YP, Gottwein JM, Scheel TK, Jensen TB and Bukh J: MicroRNA-122 antagonism against hepatitis C virus genotypes 1–6 and reduced efficacy by host RNA insertion or mutations in the HCV 5′ UTR. Proc Natl Acad Sci USA. 108:4991–4996. 2011. View Article : Google Scholar : PubMed/NCBI
20	Chomczynski P and Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 162:156–159. 1987. View Article : Google Scholar : PubMed/NCBI
21	Hu Z, Chen X, Zhao Y, et al: Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 28:1721–1726. 2010. View Article : Google Scholar : PubMed/NCBI
22	de Bruijne J, Buster EH, Gelderblom HC, et al: Treatment of chronic hepatitis C virus infection - Dutch national guidelines. Neth J Med. 66:311–322. 2008.