lncRNA Mirt2 upregulates miR-1246 through methylation to suppress LPS-induced lung cell apoptosis

Introduction: Long noncoding RNA Mirt2 has been proven to be a suppressor of lipopolysaccharide (LPS) (a key player in sepsis)-induced inflammation responses. Therefore, Mirt2 may also participate in sepsis. This study was carried out to analyze the interactions between Mirt2 and microRNA-1246 (miR-1246) in sepsis, with a specific focus on sepsis-induced acute lung injury (sepsis-ALI). Methods: Forty sepsis patients (sepsis group; 23 males and 17 females; 40-65 years, 48.6 +/- 6.3 years), 40 sepsis patients with acute lung injury (sepsis-ALI group, 23 males and 17 females; 40-65 years, 48.7 +/- 6.4 years), and 40 healthy controls (control group, 23 males and 17 females; 40-65 years, 48.6 +/- 6.1 years) were included. Mirt2 and miR-1246 expression in plasma samples from these patients were determined by a reverse transcription-quantitative polymerase chain reaction (PCR). Overexpression of Mirt2 and miR-1246 was achieved in human bronchial epithelial cells (HBEpCs) to explore the interaction between them. The effects of Mirt2 overexpression on miR-1246 methylation were analyzed by methylation-specific PCR. Cell apoptosis analysis was performed to analyze the role of Mirt2 and miR-1246 in the apoptosis of HBEpCs. Results: Mirt2 expression was downregulated in sepsis and was further downregulated in patients with sepsis-ALI. Mirt2 and miR-1246 found to be positively correlated. Downregulation of Mirt2 and miR-1246 was observed in HBEpCs with LPS treatment. In HBEpCs, Mirt2 overexpression increased miR-1246 expression but decreased its gene methylation. Cell apoptosis analysis showed that Mirt2 and miR-1246 negatively regulated the apoptosis of HBEpCs induced by LPS. In addition, miR-1246 inhibition reduced the inhibitory effects of Mirt2 overexpression on cell apoptosis. Conclusions: Mirt2 may upregulate miR-1246 through methylation to suppress lung cell apoptosis.

Automated summary

This study revealed that Mirt2 expression was downregulated in sepsis and further decreased in patients with sepsis-ALI. Mirt2 may upregulate miR-1246 through methylation to suppress lung cell apoptosis.