miRNA-155 的异位表达增强了人肝癌细胞对乙肝病毒感染的固有抗病毒免疫。

BACKGROUND

Host innate antiviral immunity is the first line of defense against viral infection, and is precisely regulated by thousands of genes at various stages, including microRNAs. MicroRNA-155 (miR-155) was found to be up-regualted during viral infection, and influence the host immune response. Besides, the expression of miR-155, or its functional orthologs, may also contribute to viral oncogenesis. HBV is known to cause hepatocellular carcinoma, and there is evidence that attenuated intracellular immune response is the main reason for HBV latency. Thus, we assume miR-155 may affect the immune response during HBV infection in human hepatoma cells.

RESULTS

We found that ectopic expression of miR-155 upregulated the expression of several IFN-inducible antiviral genes in human hepatoma cells. And over-expression of miR-155 suppressed suppressor of cytokine signaling 1 (SOCS1) expression and subsequently enhanced signal transducers and activators of transcription1 (STAT1) and signal transducers and activators of transcription3 (STAT3) phosphorylation. We further demonstrate that ectopic expression of miR-155 inhibits HBV X gene expression to some extent in vitro.

CONCLUSION

MiR-155 enhances innate antiviral immunity through promoting JAK/STAT signaling pathway by targeting SOCS1, and mildly inhibits HBV infection in human hepatoma cells.

背景

宿主先天抗病毒免疫是抵御病毒感染的第一道防线，它在包括 microRNA 在内的各个阶段受到数千个基因的精确调控。研究发现，microRNA-155（miR-155）在病毒感染过程中被上调，并影响宿主免疫反应。此外，miR-155 的表达或其功能同源物的表达也可能有助于病毒致癌。HBV 已知会导致肝细胞癌，有证据表明，细胞内免疫反应减弱是 HBV 潜伏的主要原因。因此，我们假设 miR-155 可能会影响乙型肝炎病毒感染期间人肝癌细胞的免疫反应。

结果

我们发现，miR-155 的异位表达上调了人肝癌细胞中几种 IFN 诱导的抗病毒基因的表达。并且，miR-155 的过表达抑制了细胞因子信号转导抑制因子 1（SOCS1）的表达，随后增强了信号转导和转录激活因子 1（STAT1）和信号转导和转录激活因子 3（STAT3）的磷酸化。我们进一步证明，miR-155 的异位表达在体外在一定程度上抑制了 HBV X 基因的表达。