Immunity, Inflammation and Disease (Sep 2021)

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

  • Xuwen Xu,
  • Yuyuan Xu,
  • Xin Tao,
  • Guangyu Liang

DOI
https://doi.org/10.1002/iid3.422
Journal volume & issue
Vol. 9, no. 3
pp. 695 – 701

Abstract

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Abstract 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.

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