Expression and clinical significances of lncRNA MALAT1 in Mycobacterium tuberculosis infection
Objective 
To investigate the expression and the clinical significances of a long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in Mycobacterium tuberculosis (Mtb) infection. 
 
 
Methods 
The expression of MALAT1 in peripheral blood mononuclear cells (PBMC) collected from 75 hospitalized patients with pulmonary tuberculosis (TB) and 32 healthy subjects were analyzed by real-time quantitative PCR (RT-PCR). Total RNAs were extracted from THP-1 macrophages infected with Mtb strains and the levels of MALAT1 were detected by RT-PCR. THP-1 macrophages were transfected with siRNAs to knock down the expression of MALAT1 and then were infected with Mtb strains. The levels of TNF-α and IL-6 were measured by ELISA. The entry and intracellular survival of Mtb strains in THP-1 macrophages were analyzed by bacterial culture at indicated time points. 
 
 
Results 
The relative expression level of MALAT1 in TB patients was (4.05±0.86) times that of MALAT1 in healthy controls (P 0.05). The expression of MALAT1 increased with the occurrence and extension of lung cavitation in patients with pulmonary tuberculosis (P<0.05). The levels of MALAT1 in patients with pulmonary tuberculosis were gradually down-regulated to the normal level after receiving pharmacotherapy. Results of the RT-PCR analysis indicated that the expression of MALAT1 in Mtb infected-THP-1 macrophages increased significantly (P<0.01). Higher levels of TNF-α and IL-6 were observed in Mtb infected-THP-1 macrophages with silenced expression of MALAT1 (P<0.01). Compared with the THP-1 macrophages transfected with control fragment, the survival rate of intracellular Mtb strains in THP-1 macrophages transfected with siMALAT1 was significantly decreased at the time point of 72 h. 
 
 
Conclusion 
Higher levels of MALAT1 were detected in patients with TB, which was associated with the development and outcome of TB. The intracellular killing of Mtb strains by THP-1 macrophages could be enhanced by down-regulating the expression of MALAT1. 
 
 
Key words: 
Tuberculosis; LncRNA; MALAT1; Macrophage