MicroRNA-127-5p targets the biliverdin reductase B/nuclear factor-κB pathway to suppress cell growth in hepatocellular carcinoma cells.
MicroRNA-127-5p targets the biliverdin reductase B/nuclear factor-κB pathway to suppress cell growth in hepatocellular carcinoma cells.
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DOI：
10.1111/cas.12869
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发表时间：
2016-03
期刊：
影响因子：
5.7
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Huan L;Bao C;Chen D;Li Y;Lian J;Ding J;Huang S;Liang L;He X
核因子- κB （NF - κB）激活是炎症诱导癌细胞生长和进展的主要介质之一。在之前的研究中，我们筛选了一系列靶向NF - κB信号通路的microrna （mirna）。在这项研究中，我们发现miR‐127‐5p通过抑制p65核易位来抑制NF‐κB活性。此外，miR‐127‐5p还抑制NF‐κB信号通路下游靶点的转录。在探索miR‐127‐5p抑制NF‐κB活性的机制时，我们发现miR‐127‐5p降低了p65的磷酸化。MicroRNA‐127‐5p通过直接结合其3 '‐UTR抑制肝细胞癌（HCC）细胞的生长和集落形成，并降低胆绿素还原酶B （BLVRB）的表达。RNA干扰BLVRB抑制HCC细胞生长，而过表达BLVRB促进HCC细胞生长。此外，BLVRB阻断可抑制p65蛋白磷酸化和NF‐κB信号通路下游靶点的表达，类似miR‐127‐5p的功能。在过表达miR‐127‐5p的HCC细胞中，BLVRB的恢复破坏了miR‐127‐5p对HCC生长的抑制。此外，miR - 127 - 5p在58%的HCC样本中下调。总之，我们发现miR‐127‐5p通过直接靶向HCC细胞中的BLVRB抑制NF‐κB活性，这一发现提高了我们对炎症诱导的HCC生长和增殖的分子机制的理解，以及通过癌症治疗成功抑制NF‐κB活性。
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.