Key Laboratory of Clinical Laboratory Diagnostics in Universities of Shandong, Department of Laboratory Medicine and clinical medical collegue, Weifang Medical University, Weifang, China.
Clinical Medical College, Jining Medical University, Jining, China.
J Cell Mol Med. 2020 Mar;24(5):2866-2878. doi: 10.1111/jcmm.14856. Epub 2020 Feb 12.
Tuberculosis (TB) is a severe infectious disease that seriously endangers human health. The immune defence mechanism of the body against TB is still unclear. The purpose of this study was to find the key molecules involved in the immune defence response during TB infection, and provide reference for the treatment of TB and further understanding of the immune defence mechanism of the body. Data from GSE83456 were downloaded from GEO data sets for analysis, and a total of 192 differentially expressed genes were screened out. Most of these genes are enriched in the interferon signalling pathway and are defence response-related. We also found that STAT1 plays an important role in the immune defence of TB infection and it is one of the key genes related to interferon signalling pathway. STAT1-related molecules including hsa-miR-448, hsa-miR-223-3p, SAMD8_hsa_circRNA 994 and TWF1_hsa_circRNA 9897 were therefore screened out. Furthermore, expression levels of hsa-miR-448 and hsa-miR-223-3p were then verified by qRT-PCR. Results showed that both hsa-miR-448 and hsa-miR-223-3p were down-regulated in plasma from patients with pulmonary TB. Taken together, our data indicate that an mRNA-miRNA-circRNA interaction chain may play an important role in the infection of MTB, and STAT1 and related molecules including hsa-miR-223-3p, has-miR-448, SAMD8_hsa_circRNA994 and TWF1_hsa_circRNA9897 were identified as potential biomarkers in the development of active TB.
结核病（TB）是一种严重危害人类健康的传染病。人体对结核病的免疫防御机制尚不清楚。本研究旨在寻找结核病感染过程中涉及的免疫防御反应的关键分子，为结核病的治疗提供参考，并进一步了解机体的免疫防御机制。从 GEO 数据集下载 GSE83456 中的数据进行分析，筛选出 192 个差异表达基因。这些基因大多富集在干扰素信号通路中，与防御反应相关。我们还发现 STAT1 在结核病感染的免疫防御中起着重要作用，它是与干扰素信号通路相关的关键基因之一。因此，筛选出了与 STAT1 相关的分子，包括 hsa-miR-448、hsa-miR-223-3p、SAMD8_hsa_circRNA994 和 TWF1_hsa_circRNA9897。进一步通过 qRT-PCR 验证了 hsa-miR-448 和 hsa-miR-223-3p 的表达水平。结果表明，肺结核患者血浆中 hsa-miR-448 和 hsa-miR-223-3p 的表达均下调。综上所述，我们的数据表明，mRNA-miRNA-circRNA 相互作用链可能在 MTB 感染中发挥重要作用，STAT1 及相关分子，包括 hsa-miR-223-3p、hsa-miR-448、SAMD8_hsa_circRNA994 和 TWF1_hsa_circRNA9897，可作为活动性结核病发展的潜在生物标志物。
