MiR-200b-5p as a suppressor by targeting FGF4. MicroRNA-200b-5p functions as a suppressor via directly targeting FGF4 in chronic HBV virological breakthrough

MicroRNAs (miRNAs) are some RNA molecules that negatively regulate gene expression by binding to the 3’-untranslated region (3’UTR) of target mRNA molecules. MicroRNA-200b-5p (miR-200b-5p) acts as a tumor suppressor in breast cancer, lung cancer, head and neck cancers. There is almost no data on the study of miR-200b-5p in chronic HBV (CHB) virological breakthrough, but its biological roles in CHB virological breakthrough need to dig further. In our study, we indicated that miR-200b-5p was obviously down-expressed in CHB virological breakthrough plasma and HepG2.2.15 cell using Next-generation sequencing (NGS) and Real-time quantitative reverse-transcription PCR (qRT-PCR). By Bioinformatics Analysis, we confirmed that FGF4 was an important target gene of miR-200b-5p. FGF4 was mainly involved in the transcription, DNA-templated, regulation of transcription, protein transport, protein binding, PI3K-Akt signaling pathway, pathways in cancer, focal adhesion, Ras signaling pathway, and FoxO signaling pathway by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overexpression of miR-200b-5p promoted HepG2.2.15 cell aging. Furthermore, a positive association between miR-200b-5p and FGF4 (r = 0.926, P < 0.01) was also found. FGF4 expression was negatively associated with HBV DNA (r = -0.793, P < 0.05), HBeAg (r = -0.556, P = 0.12) and HBsAg (r = -0.857, P < 0.01) using Pearson correlation analysis. These findings showed that miR-200b-5p exerts an inhibitory effect via directly targeting FGF4 in CHB virological breakthrough.