BackgroundCircular RNAs (circRNAs) contribute to the epigenetic modulation of pathological and physiological conditions. The understanding of the impact of circRNAs on generation of testicular inflammatory reactions is insufficient.MethodsOur research adopted a poly I:C-triggered testicular inflammation murine model and cell assays.ResultsMicroarray data and quantitative evaluation revealed the elevation in the concentrations of Toll-like receptor 3 (TLR3), circRNA-9119, and retinoic acid inducible gene-I (RIG-I) and repression in the levels of miR-136 and miR-26a. Inhibition of circRNA-9119 expression impaired the inflammatory reactions in the separated Leydig and Sertoli cells subjected to poly I:C treatment. CircRNA-9119 suppressed the expression of miR-136 and miR-26a by acting as a microRNA sponge. miR-136 and miR-26a repressed the expression of RIG-I and TLR3 through the expected target region in Leydig and Sertoli cells in vitro. Inhibition of miR-136 and miR-26a expression, at least in part, restored the expression of inflammatory cytokines, which were inhibited upon circRNA-9119 expression silencing. Furthermore, the expression of circRNA-9119 was positively associated with RIG-I and TLR3 mRNA and protein levels. The expression of inflammatory genes triggered by poly I:C treatment was noticeably suppressed after RIG-I and TLR3 knockout.ConclusionsOur results suggest that circRNA-9119 may serve as a competing endogenous RNA that insulated miR-136 and miR-26a and consequently defended RIG-I and TLR3 mRNAs against miR-26a/miR-136-mediated inhibition of testicular cells. Moreover, RIG-I and TLR3 contributed to the modulation of poly I:C-triggered inflammatory cytokine generation during orchitis in testicular cells.

中文翻译：

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CircRNA-9119通过TLR3和RIG-I信号通路抑制poly I:C诱导的Leydig和Sertoli细胞炎症

背景环状RNA（circRNA）有助于病理和生理条件的表观遗传调节。对circRNAs对睾丸炎症反应产生影响的理解是不够的。 方法我们的研究采用poly I：C触发的睾丸炎症小鼠模型和细胞测定。结果微阵列数据和定量评估显示Toll样受体浓度升高3 (TLR3)、circRNA-9119 和视黄酸诱导基因-I (RIG-I) 以及 miR-136 和 miR-26a 水平的抑制。circRNA-9119 表达的抑制削弱了分离的 Leydig 和 Sertoli 细胞中经过 poly I:C 处理的炎症反应。CircRNA-9119 通过充当 microRNA 海绵来抑制 miR-136 和 miR-26a 的表达。miR-136 和 miR-26a 通过体外 Leydig 和 Sertoli 细胞中预期的靶区域抑制 RIG-I 和 TLR3 的表达。抑制 miR-136 和 miR-26a 表达，至少部分恢复了炎症细胞因子的表达，这些细胞因子在 circRNA-9119 表达沉默时受到抑制。此外，circRNA-9119的表达与RIG-I和TLR3 mRNA和蛋白质水平呈正相关。在 RIG-I 和 TLR3 敲除后，poly I:C 处理引发的炎症基因的表达受到显着抑制。结论我们的结果表明，circRNA-9119 可能作为一种竞争性内源性 RNA 来隔离 miR-136 和 miR-26a，从而保护 RIG -I 和 TLR3 mRNA 对 miR-26a/miR-136 介导的睾丸细胞抑制作用。此外，RIG-I 和 TLR3 有助于 poly I 的调制：