Peripheral Circulating Exosomal-miRNAs Potentially Mediate the Sensitivity to Interferon Treatment in Chronic Hepatitis B Virus Patients.

Abstract

Pegylated interferon alfa-2b (Peg-IFN α-2b), a first-line treatment for hepatitis B virus (HBV) infection, can significantly achieve HBsAg clearance in clinic. However, only 30-40% of patients had achieved HBsAg clearance after Peg-IFN α-2b administration. The biological targets and the underline mechanisms that distinguish sensitive and insensitive populations to interferon therapy are still unclear. In the present study, only 33.33% of patients achieved HBsAg loss after 48 weeks of Peg-IFN α-2b therapy. Thirty-six exosomal-microRNAs (miRNAs) in the sensitive group were identified that might induce sensitivity specifically, whereas 32 exosomal-miRNAs in the insensitive group were identified that might induce insensitive specifically. Among these miRNAs, five miRNAs (miR-425-5p, miR-8485, miR-619-5p, miR-181a-5p, and miR-484) might increase the sensitivity to Peg-IFN α-2b therapy by regulating key genes GSK3B, KRAS, FLT1, or GRB2, whereas, 13 miRNAs (miR-195-5p, miR-215-5p, miR-9-5p, miR-130a-3p, miR-214-3p, miR-149-5p, miR-429, miR-200b-3p, miR-200c-3p, miR-16-2-3p, miR-141-3p, miR-200a-3p, and miR-218-5p) might decrease the sensitivity to Peg-IFN α-2b therapy by regulating key genes, FGF2, GSK3B, PDGFRA, FGFR1, KRAS, FLT1, MYC, TGFB2, EFNA1, MAPK9, or GRB2. Furthermore, seven novel miRNAs, namely Novel_352, Novel_459, Novel_527, Novel_677, Novel_717, Novel_749, and Novel_801 were found to be downregulated specifically in the sensitive group, whereas, Novel_142 and Novel_664 were found to be downregulated specifically in the insensitive group. Our data indicate that the serum exosomal-miRNAs could be involved in regulating the sensitivity of chronic HBV (CHB) patients to Peg-IFN α-2b therapy, which might suggest potential novel therapeutic biomarkers and standard options for CHB patients. Clinical Trials.gov ID: NCT04035837.

• Authors: Qiuju Huang, Xin Xiao, Xuerong Zhuang, Wenli Chen, Yanfang Huang, Jinyao Liao, Wensheng Wang, Ying Wang, Linlin Lu, Zhongqiu Liu, Jing Huang
• Journal: Viral immunology (Viral Immunol) Vol. 36 Issue 3 Pg. 209-221 (04 2023) ISSN: 1557-8976 [Electronic] United States
• PMID: 36944116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Circulating MicroRNA
• Hepatitis B Surface Antigens
• MIRN619 microRNA, human
• Proto-Oncogene Proteins p21(ras)
• MicroRNAs
• MIRN149 microRNA, human
• MIRN214 microRNA, human
• MIRN218 microRNA, human

Topics

• Humans
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic
• Circulating MicroRNA (therapeutic use)
• Hepatitis B Surface Antigens
• Proto-Oncogene Proteins p21(ras) (therapeutic use)
• MicroRNAs (genetics)