The Expression of lncRNA NEAT1 in Human Tuberculosis and Its Antituberculosis Effect. (11th November 2018) - Huang, Shuying
Abstract : 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-) α 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- α 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.