MicroRNA-127-5p targets the biliverdin reductase B/nuclear factor-κB pathway to suppress cell growth in hepatocellular carcinoma cells.

ABSTRACT

Nuclear factor-κB (NF-κB) activation is one of the major mediators of inflammation-induced cancer cell growth and progression. In previous studies, we screened a series of microRNAs (miRNAs) that targeted the NF-κB signaling pathway. In this study, we showed that miR-127-5p suppressed NF-κB activity through inhibition of p65 nuclear translocation. In addition, miR-127-5p also inhibited the transcription of downstream targets of the NF-κB signaling pathway. While exploring the mechanism of the inhibition of NF-κB activity by miR-127-5p, we found that miR-127-5p decreased the phosphorylation of p65. MicroRNA-127-5p inhibited the growth and colony formation of hepatocellular carcinoma (HCC) cells and decreased biliverdin reductase B (BLVRB) expression by directly binding to its 3'-UTR. RNA interference of BLVRB suppressed HCC cell growth, whereas the overexpression of BLVRB promoted HCC cell growth. Furthermore, BLVRB blockade inhibited the phosphorylation of p65 protein and the expression of downstream targets of the NF-κB signaling pathway, mimicking the function of miR-127-5p. The restoration of BLVRB in HCC cells overexpressing miR-127-5p impaired the suppression of HCC growth by miR-127-5p. Moreover, miR-127-5p was downregulated in 58% of HCC samples. In summary, we found that miR-127-5p suppressed NF-κB activity by directly targeting BLVRB in HCC cells, and this finding improves our understanding of the molecular mechanism of inflammation-induced HCC growth and proliferation and the successful inhibition of NF-κB activity by cancer treatment.