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Lu H, Gu X. MicroRNA-221 inhibits human papillomavirus 16 E1-E2 mediated DNA replication through activating SOCS1/Type I IFN signaling pathway. Int J Clin Exp Pathol. 2019;12(5):1518-1528
Lu, H., & Gu, X. (2019). MicroRNA-221 inhibits human papillomavirus 16 E1-E2 mediated DNA replication through activating SOCS1/Type I IFN signaling pathway. International journal of clinical and experimental pathology, 12(5), 1518-1528.
Lu, Haikong, and Gu, Xin. "MicroRNA-221 inhibits human papillomavirus 16 E1-E2 mediated DNA replication through activating SOCS1/Type I IFN signaling pathway." International journal of clinical and experimental pathology vol. 12,5 (2019): 1518-1528.
Lu H, Gu X. MicroRNA-221 inhibits human papillomavirus 16 E1-E2 mediated DNA replication through activating SOCS1/Type I IFN signaling pathway. Int J Clin Exp Pathol. 2019 May 01;12(5):1518-1528. eCollection 2019. PMID: 31933969; PMCID: PMC6947112.
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Int J Clin Exp Pathol. 2019 May 01;12(5):1518-1528. eCollection 2019.

MicroRNA-221 inhibits human papillomavirus 16 E1-E2 mediated DNA replication through activating SOCS1/Type I IFN signaling pathway.

International journal of clinical and experimental pathology

Haikong Lu, Xin Gu

Affiliations

  1. Department of Sexually Transmitted Disease Institute, Shanghai Skin Disease Hospital Shanghai 200050, China.

PMID: 31933969 PMCID: PMC6947112

Abstract

Human Papillomavirus (HPV) 16 infection has led to clinical disorders and is considered one of the important causes of human cervical cancer. Recently, microRNAs (miRNAs) have been proven to play an important role in many viral infections through regulating the Type I IFN immune response. However, reports concerning the role of miRNAs in HPV 16 infection are unclear. The aim of this study was to identify and evaluate the potential functions of miRNAs in HPV 16 replication and reveal the detailed mechanism for regulating IFN immune response. Using microarray and qRT-PCR assays, microRNA-221 (miR-221) was found to be significantly up-regulated in the serum samples from patients with HPV 16 infection, as well as in HPV 16-positive cervical cancer cells. miR-221 overexpression inhibited, while miR-221 knockdown facilitated HPV 16 E1-E2 mediated DNA replication in vitro. Moreover, overexpression of miR-221 was associated with upregulation of IFN-α and IFN-β at mRNA and protein levels in infected cells. Conversely, IFN-α and IFN-β mRNA or protein expression was significantly downregulated during inhibition of miR-221. Subsequently, we demonstrated that upregulation of miR-221 promoted the expression of representative interferon stimulated genes (ISGs) such as myxovirus protein A (MxA), 2',5'-oligoadenylate synthetases (OAS) and murine IFN-stimulated gene 15 (ISG15). In contrast, miR-221 inhibition significantly decreased ISGs expression. Furthermore, we found that suppressor of cytokine signaling 1 (SOCS1), a suppressor of interferon signaling pathway, was a direct target of miR-221 and overexpression of SOCS1 reversed the effects of miR-221 on the IFN-I response and HPV 16 E1-E2 mediated DNA replication. Collectively, the findings provide new evidence that miR-221 could inhibit HPV 16 E1-E2 mediated DNA replication through the SOCS1/Type I IFN signaling pathway suggesting it may be a novel anti-HPV therapeutic target.

IJCEP Copyright © 2019.

Keywords: DNA replication; Human papillomavirus 16; SOCS1/Type I IFN signaling pathway; microRNA-221

Conflict of interest statement

None.

References

  1. Hepatology. 2011 Sep 2;54(3):808-19 - PubMed
  2. J Virol. 2011 Mar;85(5):1912-21 - PubMed
  3. Nat Med. 2007 Oct;13(10):1241-7 - PubMed
  4. J Immunol Res. 2015;2015:738547 - PubMed
  5. Methods Mol Med. 2005;119:349-62 - PubMed
  6. Int J Cancer. 2004 Apr 10;109(3):418-24 - PubMed
  7. Dev Comp Immunol. 2014 Jul;45(1):177-89 - PubMed
  8. Nature. 2004 Sep 16;431(7006):350-5 - PubMed
  9. Virology. 2018 Jun;519:121-130 - PubMed
  10. Curr Opin Virol. 2011 Dec;1(6):519-25 - PubMed
  11. Ann Oncol. 2011 Dec;22(12):2675-86 - PubMed
  12. Nat Rev Immunol. 2008 Jul;8(7):559-68 - PubMed
  13. FEBS Open Bio. 2018 Aug 29;8(9):1457-1470 - PubMed
  14. Biochem Biophys Res Commun. 2011 Aug 19;412(1):20-5 - PubMed
  15. Med Sci (Basel). 2016 May 13;4(2):null - PubMed
  16. Cell Rep. 2017 Oct 3;21(1):141-153 - PubMed
  17. Exp Cell Res. 2018 Aug 15;369(2):197-207 - PubMed
  18. Blood. 2011 Apr 21;117(16):4293-303 - PubMed
  19. PLoS One. 2014 Dec 02;9(12):e114021 - PubMed
  20. J Viral Hepat. 2014 Feb;21(2):121-8 - PubMed
  21. Antiviral Res. 2010 Nov;88(2):169-75 - PubMed
  22. Virology. 2014 Aug;462-463:343-50 - PubMed
  23. N Engl J Med. 2003 Feb 6;348(6):518-27 - PubMed
  24. Viral Immunol. 2018 Dec 1;31(10):676-682 - PubMed
  25. Biomed Pharmacother. 2018 Jan;97:1409-1416 - PubMed
  26. Cell. 2009 Jan 23;136(2):215-33 - PubMed
  27. Antiviral Res. 2013 Feb;97(2):101-7 - PubMed
  28. Clin Cancer Res. 2010 Feb 1;16(3):957-66 - PubMed
  29. J Immunol. 2008 Feb 15;180(4):2034-8 - PubMed
  30. J Virol. 2013 Jan;87(2):1159-71 - PubMed
  31. J Virol. 2012 Dec;86(23):12806-15 - PubMed
  32. J Virol. 2009 May;83(9):4127-39 - PubMed
  33. J Virol. 2012 Sep;86(18):10221-5 - PubMed
  34. J Infect. 2013 Oct;67(4):329-41 - PubMed
  35. Virus Res. 2015 Jan 22;196:135-9 - PubMed
  36. Cell. 2004 Jan 23;116(2):281-97 - PubMed
  37. Hepatology. 2012 Mar;55(3):730-41 - PubMed
  38. Virology. 2003 Oct 10;315(1):103-9 - PubMed
  39. Cancer Res. 2009 Jun 1;69(11):4878-84 - PubMed

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