LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis
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RESEARCH ARTICLE
Molecular Medicine
Open Access
LncRNA LUADT1 sponges miR‑195 to prevent cardiac endothelial cell apoptosis in sepsis Zhimin Zhang1†, Mingzhu Lv3†, Xiang Wang1, Zheng Zhao2, Daolong Jiang2 and Lihua Wang2*
Abstract Background: The oncogenic role of the newly identified lncRNA LUADT1 has been revealed in lung adenocarcinoma. It was reported that LUADT1 plays a critical role in multiple human diseases. This study was carried out to investigate the role of LUADT1 in sepsis. Methods: Sixty patients with sepsis and sixty healthy volunteers were recruited for this study. Plasma samples were collected from all participants. Human primary coronary artery endothelial cells were also used in this study. The expression of Pim-1, miR-195 and LUADT1 were detected by RT-qPCR. The interaction between miR-195 and LUADT1 was determined by overexpression experiments and luciferase activity assay. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related protein was detected by Western blotting. Results: Bioinformatics analysis revealed the potential interaction between LUADT1 and miR-195, which was confirmed by dual luciferase reporter assay. LUADT1 was downregulated in patients with sepsis. Moreover, LPS treatment downregulated the expression of LUADT1 in primary cardiac endothelial cells. Overexpression of LUADT1 and miR195 did not affect the expression of each other in primary cardiac endothelial cells. Interestingly, overexpression of LUADT1 was found to upregulate the expression of Pim-1, a target of miR-195. In addition, it was found that overexpression of LUADT1 and Pim-1 reduced the enhancement effects of miR-195 on LPS-induced cardiac endothelial cell apoptosis. Conclusion: In summary, LUADT1 may protect cardiac endothelial cells against apoptosis in sepsis by regulating the miR-195/Pim-1 axis. Keywords: Sepsis, LUADT1, miR-195, Cardiac endothelial cells, Pim-1, Apoptosis Introduction Sepsis is a common and lethal clinical syndrome that occurs when severe systemic responses of body to infection, resulting in injury to its own tissues and organs (Cohen et al. 2015). Sepsis mostly affects elderly and patients complicated with other severe diseases, such *Correspondence: [email protected] † Zhimin Zhang and Mingzhu Lv contributed equally to this work 2 Department of Clinical Laboratory, Affliated Dongfeng Hospital, Hubei University of Medicine, Shiyan 442008, Hubei, People’s Republic of China Full list of author information is available at the end of the article
as cancer (Gotts and Matthay 2016). The development of sepsis causes the dysfunction of multiple organs and induces critical illness characterized by severe immune dysfunction and catabolism (Gotts and Matthay 2016). Multiple therapeutic approaches have shown promising efficacy in improving the conditions of sepsis animal model, and some approaches are under clinical validation (Hotchkiss and Karl 2003; Riedemann et al. 2003; Cronin et al. 1995). However, antibiotics, which are correlated with the high prevalence of res
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