MicroRNA-127-5p targets the biliverdin reductase B/nuclear factor-κB pathway to suppress cell growth in hepatocellular carcinoma cells.
Bottom Line: 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.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.
Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Show MeSH
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Mentions: The biological function of BLVRB in HCC remains unclear. As a target of miR‐127‐5p in HCC, we first determined whether BLVRB influences NF‐κB activation. Biliverdin reductase B siRNAs were cotransfected with a luciferase reporter plasmid containing NF‐κB binding sites into SMMC‐7721 and SNU‐449 cells. The luciferase reporter assays indicated that BLVRB siRNAs decreased NF‐κB activity (Fig. 5a,b). In addition, knockdown of BLVRB also inhibited the expression of NF‐κB downstream targets (Fig. 5c), the nuclear translocation of p65 (Fig. 5d), and significantly suppressed the proliferation of HCC cells (Fig. 5e). Then, we obtained a lentiviral vector harboring the ORF of BLVRB and used it to establish SMMC‐7721 and SNU‐449 cell lines that stably expressed the ORF of BLVRB (Fig. S5). The CCK‐8 assays indicated that ectopic expression of BLVRB facilitated the proliferation of HCC cells (Fig. 6a).
Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.