Institute of Forensic Medicine, Soochow University, Suzhou 215021, China.
Department of Pathology, School of Medicine, Shihezi University, Shihezi 215021, China.
Int J Mol Sci. 2019 Jan 18;20(2):407. doi: 10.3390/ijms20020407.
Adenosine deaminases acting on RNA (ADAR) are enzymes that regulate RNA metabolism through post-transcriptional mechanisms. ADAR1 is involved in a variety of pathological conditions including inflammation, cancer, and the host defense against viral infections. However, the role of ADAR1p150 in vascular disease remains unclear. In this study, we examined the expression of ADAR1p150 and its role in viral myocarditis (VMC) in a mouse model. VMC mouse cardiomyocytes showed significantly higher expression of ADAR1p150 compared to the control samples. Coimmunoprecipitation verified that ADAR1p150 forms a complex with Dicer in VMC. miRNA-222, which is involved in many cardiac diseases, is highly expressed in cardiomyocytes in VMC. In addition, the expression of miRNA-222 was promoted by ADAR1p150/Dicer. Among the target genes of miRNA-222, the expression of phosphatase-and-tensin (PTEN) protein was significantly reduced in VMC. By using a bioinformatics tool, we found a potential binding site of miRNA-222 on the PTEN gene's 3'-UTR, suggesting that miRNA-222 might play a regulatory role. In cultured cells, miR-222 suppressed PTEN expression. Our findings suggest that ADAR1p150 plays a key role in complexing with Dicer and promoting the expression of miRNA-222, the latter of which suppresses the expression of the target gene PTEN during VMC. Our work reveals a previously unknown role of ADAR1p150 in gene expression in VMC.
腺嘌呤脱氨酶作用于 RNA（ADAR）是通过转录后机制调节 RNA 代谢的酶。ADAR1 参与多种病理状况，包括炎症、癌症和宿主防御病毒感染。然而，ADAR1p150 在血管疾病中的作用尚不清楚。在这项研究中，我们在小鼠模型中检查了 ADAR1p150 的表达及其在病毒性心肌炎（VMC）中的作用。VMC 小鼠心肌细胞与对照样本相比，ADAR1p150 的表达显著升高。共免疫沉淀验证了 ADAR1p150 在 VMC 中与 Dicer 形成复合物。miRNA-222 参与许多心脏疾病，在 VMC 中的心肌细胞中高度表达。此外，ADAR1p150/Dicer 促进了 miRNA-222 的表达。在 miRNA-222 的靶基因中，PTEN 蛋白的表达在 VMC 中显著降低。通过使用生物信息学工具，我们在 PTEN 基因的 3'-UTR 上发现了 miRNA-222 的一个潜在结合位点，表明 miRNA-222 可能发挥调节作用。在培养的细胞中，miR-222 抑制了 PTEN 的表达。我们的研究结果表明，ADAR1p150 在与 Dicer 形成复合物并促进 miRNA-222 的表达方面发挥关键作用，后者在 VMC 期间抑制靶基因 PTEN 的表达。我们的工作揭示了 ADAR1p150 在 VMC 中基因表达中的一个先前未知的作用。
