MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1? and PPAR?.

ABSTRACT: In hepatitis B virus (HBV)-replicating hepatocytes, miR-130a expression was significantly reduced. In a reciprocal manner, miR-130a reduced HBV replication by targeting at two major metabolic regulators PGC1? and PPAR?, both of which can potently stimulate HBV replication. We proposed a positive feed-forward loop between HBV, miR-130a, PPAR?, and PGC1?. Accordingly, HBV can significantly enhance viral replication by reducing miR-130a and increasing PGC1? and PPAR?. NF-?B/p65 can strongly stimulate miR-130a promoter, while miR-130a can promote NF-?B/p65 protein level by reducing PPAR? and thus NF-?B/p65 protein degradation. We postulated another positive feed-forward loop between miR-130a and NF-?B/p65 via PPAR?. During liver inflammation, NF-?B signaling could contribute to viral clearance via its positive effect on miR-130a transcription. Conversely, in asymptomatic HBV carriers, persistent viral infection could reduce miR-130a and NF-?B expression, leading to dampened inflammation and immune tolerance. Finally, miR-130a could contribute to metabolic homeostasis by dual targeting PGC1? and PPAR? simultaneously.

SUBMITTER: Huang JY 

PROVIDER: S-EPMC4338335 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature