环状 RNA hsa_circ_0004812 通过海绵吸附 miR-1287-5p 来调节慢性乙型肝炎中的 FSTL1，从而损害 IFN 诱导的免疫反应。

Circular RNA hsa_circ_0004812 impairs IFN-induced immune response by sponging miR-1287-5p to regulate FSTL1 in chronic hepatitis B.

机构信息

Second Department of Infectious Diseases, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061001, Hebei Province, China.

出版信息

Virol J. 2020 Mar 18;17(1):40. doi: 10.1186/s12985-020-01314-0.

BACKGROUND

The present study aims to explore the functions of circular RNA hsa_circ_0004812 in chronic hepatitis B (CHB) and its underlying molecular mechanisms.

METHODS

The expression of circular RNA (circRNA)_0004812 was examined using qRT-PCR and Western blot in blood and liver tissues from CHB patients and healthy volunteers. In the in vitro study, the expression levels of circular RNA hsa_circ_0004812, miR-1287-5p, interferon (IFN)-α, IFN-β were determined using qRT-PCR and Western blotting in HBV-infected hepatoma cells, respectively. Luciferase and biotin pull-down assays were used to investigate the interactions between miR-1287-5p and circ_0004812.

RESULTS

Levels of circ_0004812 were upregulated in CHB patients and HBV-infected hepatoma cells. Knockdown of circ_0004812 increased the expression of IFN-α and IFN-β in HBV-infected Huh7 cells. MiR-1287-5p was identified as a target of circ_0004812 whose overexpression inhibited the expression of miR-1287-5p. Additionally, circ_0004812 promoted the expression of Follistatin-related protein (FSTL) 1 through inhibiting miR-1287-5p. Circ_0004812/miR-1287-5p/FSTL1 axis regulated HBV-induced immune suppression.

CONCLUSION

Circ_0004812 was identified as a potential target for CHB infection. Circ_0004812 promoted the expression of FSTL1 by inhibiting miR-1287-5p.

背景

本研究旨在探讨环状 RNA hsa_circ_0004812 在慢性乙型肝炎（CHB）中的功能及其潜在的分子机制。

方法

采用 qRT-PCR 和 Western blot 检测 CHB 患者和健康志愿者血和肝组织中环状 RNA（circRNA）_0004812 的表达。在体外研究中，分别采用 qRT-PCR 和 Western blot 检测 HBV 感染的肝癌细胞中环状 RNA hsa_circ_0004812、miR-1287-5p、干扰素（IFN）-α、IFN-β的表达水平。采用荧光素酶和生物素下拉实验研究 miR-1287-5p 与 circ_0004812 之间的相互作用。

结果

CHB 患者和 HBV 感染的肝癌细胞中 circ_0004812 水平上调。circ_0004812 敲低可增加 HBV 感染的 Huh7 细胞中 IFN-α和 IFN-β的表达。miR-1287-5p 被鉴定为 circ_0004812 的靶基因，其过表达抑制 miR-1287-5p 的表达。此外，circ_0004812 通过抑制 miR-1287-5p 促进 Follistatin 相关蛋白（FSTL）1 的表达。circ_0004812/miR-1287-5p/FSTL1 轴调节 HBV 诱导的免疫抑制。