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宁先会, 韩冰, 彭冶, 尹绍武. 2024: LncRNA pol-lnc78作为ceRNA通过抑制pol-mir-n199-3p介导的SARM表达下调从而调控牙鲆的抗菌反应. 动物学研究, 45(1): 25-35. DOI: 10.24272/j.issn.2095-8137.2022.520
引用本文: 宁先会, 韩冰, 彭冶, 尹绍武. 2024: LncRNA pol-lnc78作为ceRNA通过抑制pol-mir-n199-3p介导的SARM表达下调从而调控牙鲆的抗菌反应. 动物学研究, 45(1): 25-35. DOI: 10.24272/j.issn.2095-8137.2022.520
Xian-Hui Ning, Bing Han, Ye Peng, Shao-Wu Yin. 2024. LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus. Zoological Research, 45(1): 25-35. DOI: 10.24272/j.issn.2095-8137.2022.520
Citation: Xian-Hui Ning, Bing Han, Ye Peng, Shao-Wu Yin. 2024. LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus. Zoological Research, 45(1): 25-35. DOI: 10.24272/j.issn.2095-8137.2022.520

LncRNA pol-lnc78作为ceRNA通过抑制pol-mir-n199-3p介导的SARM表达下调从而调控牙鲆的抗菌反应

LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus

  • 摘要: LncRNAs(长链非编码RNAs),特别是lncRNAs介导的ceRNAs(竞争性内源性RNA),已成为哺乳动物关键的免疫调节因子。目前,对低等脊椎动物lncRNA的研究仍处于起步阶段。在该研究中,我们在硬骨鱼牙鲆(Paralichthys olivaceus)中鉴定到第一个免疫相关的lncRNA,称为pol-lnc78。我们发现pol-lnc78可作为ceRNA介导pol-miR-n199-3p调节SARM(最新发现的TLR信号通路配体)。并且,这一ceRNA调控元能够通过TLR信号通路调节牙鲆的抗菌反应。具体来说,SARM作为负调节因子,通过抑制炎症因子IL-1β和TNF-α的表达,从而加剧细菌感染。Pol-miR-n199-3p通过与3'UTR区特异性结合降低SARM表达,从而促进SARM介导的炎症因子的表达,起到抑制细菌扩散和保护宿主的作用。进一步研究发现,pol-lnc78能够竞争性结合pol-miR-n199-3p,进而缓解其对SARM的表达抑制。在细菌感染过程中,负调节因子pol-lnc78和SARM的表达显著下调,pol-miR-n199-3p的表达显著上调,从而增强宿主的抗菌防御反应。研究结果为鱼类免疫机制提供了新的见解,同时,为更深入地理解低等脊椎动物的ceRNA调控机制提供了新的视角。

     

    Abstract: Long non-coding RNAs (lncRNAs) function as key modulators in mammalian immunity, particularly due to their involvement in lncRNA-mediated competitive endogenous RNA (ceRNA) crosstalk. Despite their recognized significance in mammals, research on lncRNAs in lower vertebrates remains limited. In the present study, we characterized the first immune-related lncRNA (pol-lnc78) in the teleost Japanese flounder (Paralichthys olivaceus). Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein (SARM), the fifth discovered member of the Toll/interleukin 1 (IL-1) receptor (TIR) adaptor family. This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor (TLR) signaling pathway. Specifically, SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1β and tumor necrosis factor-α (TNF-α). Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’ untranslated region (UTR), thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination. Furthermore, pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression. During infection, the negative regulators pol-lnc78 and SARM were significantly down-regulated, while pol-miR-n199-3p was significantly up-regulated, thus favoring host antibacterial defense. These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.

     

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