Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Huazhong Agricultural University, Wuhan, China.
Front Immunol. 2022 Jun 27;13:887602. doi: 10.3389/fimmu.2022.887602. eCollection 2022.
(MG) is one of the most important pathogens, that causes chronic respiratory disease (CRD) in chickens. Long non-coding RNAs (lncRNAs) are emerging as new regulators for many diseases and some lncRNAs can function as competing endogenous RNAs (ceRNAs) to regulate mRNAs by competitively binding to miRNAs. Here, we found that miR-33-5p was significantly up-regulated both in MG-infected chicken embryonic lungs and chicken embryo fibroblast cells (DF-1), and Lnc90386 negatively correlated with miR-33-5p. miR-33-5p, as a new regulator for MG infection, repressed apoptosis, inflammatory factors in DF-1 cells by targeting JNK1. Further analyses showed that Lnc90386 sponged miR-33-5p to weaken its inhibitory effect on JNK1, forming the ceRNA regulatory network. Furthermore, knockdown of Lnc90386 significantly inhibited apoptosis and inflammatory factors, and promoted DF-1 cells proliferation. However, co-treatment with miR-33-5p inhibitor and Lnc90386 siRNA showed that knockdown of Lnc90386 could partially eliminate the inhibiting effect of miR-33-5p inhibitor on inflammation, cell apoptosis and proliferation. In conclusion, Lnc90386 sponges miR-33-5p to defend against MG infection by inhibiting the JNK signaling pathway.
(MG)是引起鸡慢性呼吸道病(CRD)的最重要病原体之一。长链非编码 RNA(lncRNA)作为许多疾病的新调节剂而出现,一些 lncRNA 可以作为竞争性内源性 RNA(ceRNA)通过竞争性结合 miRNAs 来调节 mRNAs。在这里,我们发现 miR-33-5p 在 MG 感染的鸡胚肺和鸡胚成纤维细胞(DF-1)中均显著上调,并且 Lnc90386 与 miR-33-5p 呈负相关。miR-33-5p 作为 MG 感染的新调节剂,通过靶向 JNK1 抑制 DF-1 细胞中的凋亡和炎性因子。进一步分析表明,Lnc90386 海绵吸附 miR-33-5p 以减弱其对 JNK1 的抑制作用,形成 ceRNA 调控网络。此外,敲低 Lnc90386 可显著抑制细胞凋亡和炎性因子,并促进 DF-1 细胞增殖。然而,miR-33-5p 抑制剂和 Lnc90386 siRNA 的共同处理表明,敲低 Lnc90386 可以部分消除 miR-33-5p 抑制剂对炎症、细胞凋亡和增殖的抑制作用。总之,Lnc90386 通过抑制 JNK 信号通路来吸附 miR-33-5p 以抵抗 MG 感染。