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

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.

Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity

“…The functions of these upregulated miRNAs are listed in Additional file 1: Table S1. Among these molecules, miR-1246, which showed the highest upregulation, has been proven to be involved in immune regulation [32], inhibition of angiogenesis [33], inhibition of cell apoptosis [34], promotion of cell migration [35], and promotion of M2 polarization of macrophages [36], and it is expressed at high levels during the chondrogenic differentiation of stem cells [37]; thus, miR-1246 potentially plays positive regulatory role in stem cell chondrogenic differentiation. Through GO enrichment analysis and KEGG enrichment analysis of the upregulated miRNAs, we found that these miRNAs are involved in various regulatory processes that are related to cartilage regeneration as well as the regulation of stem cell proliferation and chondrogenic differentiation.…”

Regulatory role of noncoding RNA in sepsis and sepsis-associated organ dysfunction: an updated systematic review

“…For example, Gao et al (8) showed that upregulated exosomal miR-1-3p can inhibit cell proliferation, promote apoptosis and cytoskeleton contraction, and increase the permeability of monolayer endothelial cells and membrane injury by targeting SERP1; consequently, the endothelial cells become dysfunctional, and the vascular barrier functions involved in the development of ALI may weaken. Moreover, a limited number of studies have investigated the modification of lncRNAs; for instance, Xu and colleagues (9) found that lncRNA Mirt2 suppresses LPS-induced lung cell apoptosis by upregulating miR-1246 through methylation. Zhou et al (10) used the serum of patients with sepsis (n = 85) and healthy controls (n = 76) to assess the diagnostic value of lncRNA H19 and established a sepsis-induced ALI rat model treated with lncRNA to determine the underlying molecular mechanisms.…”