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长链非编码 RNA STAT4-AS1 通过靶向 RORt 蛋白抑制 TH17 细胞分化。

lncRNA STAT4-AS1 Inhibited TH17 Cell Differentiation by Targeting RORt Protein.

机构信息

Department of Medical Microbiology, Central South University, Changsha, 410078 Hunan, China.

Department of Obstetrics, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Hunan, China.

出版信息

J Immunol Res. 2022 Apr 28;2022:8307280. doi: 10.1155/2022/8307280. eCollection 2022.

DOI:10.1155/2022/8307280
PMID:35528611
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9071868/
Abstract

OBJECTIVE

From our previous study, we obtained long noncoding RNA (lncRNA) STAT4-AS1, which is related to asthma through high-throughput screening. However, we could not determine the specific mechanism involved and in response to this. We further designed this study.

RESULTS

First, we found that lncRNA STAT4-AS1 was downregulated in T cells from patients with asthma when compared to healthy controls. Next, we confirmed that lncRNA STAT4-AS1 was significantly negatively correlated with T helper 17 (TH17) differentiation in vitro experiments. The decreases of STAT4-AS1 promoted TH17 differentiation, while the increases of STAT4-AS1 inhibited TH17 differentiation. Subsequently, through RNA pull-down, RNA-binding protein immunoprecipitation (RIP), and dual luciferase reporter assay, we found that STAT4-AS1 could inhibit the binding of retinoid-related orphan receptor-t (RORt) protein with an IL-17A promoter after binding with RORt protein. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic separation assay showed that STAT4-AS1 is bonded to RORt in the cytoplasm, preventing RORt from entering the nucleus.

CONCLUSION

Overall, STAT4-AS1 directly targets RORt protein, inhibits the mutual binding of RORt and IL-17 gene promoter, and eventually inhibits TH17 differentiation. To this end, STAT4-AS1 as a potential target may confer applications in the clinical treatment and diagnosis of TH17-related diseases.

摘要

目的

在我们之前的研究中，通过高通量筛选获得了与哮喘相关的长链非编码 RNA（lncRNA）STAT4-AS1，但我们无法确定其中涉及的具体机制。因此，我们进一步设计了这项研究。

结果

首先，我们发现与健康对照组相比，哮喘患者的 T 细胞中 lncRNA STAT4-AS1 表达下调。其次，我们在体外实验中证实 lncRNA STAT4-AS1 与辅助性 T 细胞 17（TH17）分化呈显著负相关。降低 STAT4-AS1 可促进 TH17 分化，而增加 STAT4-AS1 则可抑制 TH17 分化。随后，通过 RNA 下拉、RNA 结合蛋白免疫沉淀（RIP）和双荧光素酶报告基因检测，我们发现 STAT4-AS1 可与 RORt 蛋白结合后抑制 RORt 蛋白与 IL-17A 启动子的结合。荧光原位杂交（FISH）和核质分离实验表明，STAT4-AS1 与 RORt 在细胞质中结合，阻止 RORt 进入细胞核。

结论

综上所述，STAT4-AS1 可直接靶向 RORt 蛋白，抑制 RORt 与 IL-17 基因启动子的相互结合，从而最终抑制 TH17 分化。为此，STAT4-AS1 作为一种潜在的靶点，可能在 TH17 相关疾病的临床治疗和诊断中具有应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/7e72e317e036/JIR2022-8307280.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/c9c7d52f5dc8/JIR2022-8307280.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/c02b72ccd286/JIR2022-8307280.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/65bcd683f010/JIR2022-8307280.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/de839fb87f9f/JIR2022-8307280.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/c933b9373a05/JIR2022-8307280.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/54080a0247b6/JIR2022-8307280.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/7e72e317e036/JIR2022-8307280.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/c9c7d52f5dc8/JIR2022-8307280.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/c02b72ccd286/JIR2022-8307280.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/65bcd683f010/JIR2022-8307280.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/de839fb87f9f/JIR2022-8307280.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/c933b9373a05/JIR2022-8307280.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/54080a0247b6/JIR2022-8307280.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b16/9071868/7e72e317e036/JIR2022-8307280.007.jpg

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