Alteration of microRNA profiles by a novel inhibitor of human La protein in HBV-transformed human hepatoma cells.

A pyrazolopyridine HBSC11 was previously identified as a novel inhibitor of human La protein with anti-hepatitis B virus (HBV) activity. However, the underlying mechanism(s) of HBV inhibition by HBSC11 remains unclear. This study aimed to examine the regulation of microRNA (miRNA) by HBSC11 in HBV-transformed human hepatoma HepG2.2.15 cells using microarray and quantitative real-time PCR. Target genes of the differentially expressed miRNAs were predicted and subjected to bioinformatics analysis. Results showed that HBSC11 significantly upregulated the expression of miR-3912-5p, miR-6793-5p, and miR-7159-5p in HepG2.2.15 cells. Target genes of the three miRNAs were mainly involved in the regulation of nucleic acid-templated transcription, negative regulation of gene expression, nucleic acid binding transcription factor activity and regulation of phosphorylation. In addition, target genes were enriched in certain regulatory pathways related to HBV infection and HBV-associated disease progression, such as the transforming growth factor (TGF)-β, Wnt, and p53 signaling. Our study demonstrates the involvement of miR-3912-5p, miR-6793-5p, and miR-7159-5p and the potential modulation of specific pathways (TGF-β, Wnt, and p53 signaling) in HBSC11-mediated inhibition of HBV replication. This study provides insight into the molecular mechanism of the action of HBSC11 against HBV infection and will support the development of antiviral drugs targeting La protein.