Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006 Jiangxi, China.
Department of Nursing, Jiangxi Health Vocational College, Nanchang, 330052 Jiangxi, China.
Biomed Res Int. 2018 Nov 11;2018:9529072. doi: 10.1155/2018/9529072. eCollection 2018.
Increasing evidence suggests that lncRNA is important in innate immune responses. Recent study has demonstrated that lncRNA NEAT1 (which has two subtypes: NEAT1_1 and NEAT1_2) nuclear-enriched abundant transcript 1 (NEAT1) is essential in immune regulation, but the expression and clinical significance in tuberculosis are still unclear. In this work, we aimed to discuss the expression and clinical significance of NEAT1 in tuberculosis patients. Quantitative real-time polymerase chain reaction was performed to detect the expression of NEAT1 (both NEAT1_1 and NEAT1_2) in peripheral blood mononuclear cells (PBMCs) of patients with tuberculosis and healthy controls and analyze the association of NEAT1 with the development, progression, and outcome of tuberculosis. Then NEAT1 was silenced in THP-1 cells using siRNA. The expression of tumor necrosis factor- (TNF-) and interleukin- (IL-) 6 was detected after Mycobacterium tuberculosis (Mtb) infection, and the change in bactericidal capacity against Mtb was assessed. We demonstrated that the relative expression of NEAT1 (both NEAT1_1 and NEAT1_2) in patients with tuberculosis was higher than that in the control. However, the expression of NEAT1 (both NEAT1_1 and NEAT1_2) in the new case and relapse groups had insignificant differences. The level of NEAT1 (both NEAT1_1 and NEAT1_2) in PBMCs declined gradually with treatment and was restored to the normal level. The expression of NEAT1 (both NEAT1_1 and NEAT1_2) in THP-1 cells increased markedly after Mtb infection. The levels of IL-6 but not TNF- in Mtb-infected THP-1 cells declined after the NEAT1 (both NEAT1_1 and NEAT1_2) knockout. The survival of Mtb in NEAT1-knockout (both NEAT1_1 and NEAT1_2) THP-1 cells reached its peak 72 h after infection, taking 0 h after Mtb infection as the baseline data; the difference was statistically significant compared with the control. Thus, our results indicate that the expression of NEAT1 increased during Mtb infection, and it might be associated with the outcome of tuberculosis. The decreased expression of NEAT1 might weaken the clearance of intracellular Mtb by macrophages.
越来越多的证据表明 lncRNA 在先天免疫反应中发挥着重要作用。最近的研究表明,富含核的长链非编码 RNA 1(lncRNA NEAT1,具有两个亚型:NEAT1_1 和 NEAT1_2)是免疫调节所必需的,但在结核病中的表达和临床意义尚不清楚。在这项工作中,我们旨在探讨结核病患者中 NEAT1 的表达及其临床意义。通过定量实时聚合酶链反应检测结核病患者和健康对照者外周血单个核细胞(PBMCs)中 NEAT1(包括 NEAT1_1 和 NEAT1_2)的表达,并分析 NEAT1 与结核病的发生、发展和结局的关系。然后,用 siRNA 沉默 THP-1 细胞中的 NEAT1。在感染结核分枝杆菌(Mtb)后检测肿瘤坏死因子-(TNF-)和白细胞介素-(IL-)6 的表达,并评估对 Mtb 的杀菌能力的变化。结果表明,结核病患者中 NEAT1(包括 NEAT1_1 和 NEAT1_2)的相对表达高于对照组。然而,新发和复发组中 NEAT1(包括 NEAT1_1 和 NEAT1_2)的表达无显著差异。随着治疗的进行,PBMCs 中 NEAT1(包括 NEAT1_1 和 NEAT1_2)的水平逐渐下降,并恢复到正常水平。Mtb 感染后 THP-1 细胞中 NEAT1(包括 NEAT1_1 和 NEAT1_2)的表达明显增加。感染 Mtb 后,敲除 NEAT1(包括 NEAT1_1 和 NEAT1_2)后 Mtb 感染的 THP-1 细胞中 IL-6 的水平而非 TNF-的水平下降。与对照组相比,NEAT1 敲除(包括 NEAT1_1 和 NEAT1_2)的 THP-1 细胞中 Mtb 的存活在感染后 72 小时达到峰值,以 Mtb 感染 0 小时为基线数据,差异具有统计学意义。因此,我们的研究结果表明,在 Mtb 感染过程中 NEAT1 的表达增加,可能与结核病的结局有关。NEAT1 表达水平的降低可能会削弱巨噬细胞对细胞内 Mtb 的清除。