Acute Liver Failure

Oral Presentations

Abstract # 371

MicroRNA-181c potentially relieved fulminant viral hepatitis by targeting TNF-a

Xi Dong, Wang Ming, Yang Muyang, XuMengyin, Wang Faxi, Ding Wen, Ma Wenwen, Ning Qin

Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and
Technology. Wuhan, China

Objectives: The relationship between circulating microRNAs (miRNAs) and HBV associated acute-on-chronic liver failure (HBVACLF) need to be further investigated. The purpose of our study was to identify the aberrant expression of miRNAs in HBV-ACLF and to investigate its potential role during the progression of HBV-ACLF.

Methods: miRNA expression profile by miRNA microarray analysis was performed on Peripheral Blood Mononuclear Cell (PBMC) obtained from patients with mild chronic hepatitis B (CHB) or HBVACLF, respectively. Selected unnormal expressed miRNAs were verified in more clinical samples by quantitative real-time PCR (qRTPCR).
A luciferase reporter assay was conducted to confirm direct target of miR-181c. mmu-miR-181c agomir was delivered by tail vein injection into mouse hepatitis virus-3(MHV-3)-infected BALB/cJ mice to evaluate its interference effect in fulminant viral hepatitis mouse model.

Results: 7 kinds of miRNAs were down-regulated and 9 kinds of miRNAs were up-regulated in the PBMC of HBV-ACLF patients compared with that of patients with mild CHB. Among the deregulated miRNAs, the expression of Hsa-miRNA-181c was significantly down-regulated in HBV-ACLF by qRT-PCR. While serum TNF-a significantly increased in HBV-ACLF. A luciferase reporter assay was conducted to confirm TNF-a was verified as a target of miR-181c. miR-181c significantly improved fulminant viral hepatitis mice survival rate.

Conclusion: These data suggested that miR-181c might have potentially therapeutic potential for the treatment of fulminant
hepatitis.