RETRACTED: Targeting MALAT1 and miRNA-181a-5p for the intervention of acute lung injury/acute respiratory distress syndrome

Abstract

Background: ALI/ARDS is a severe lung injury leading to refractory respiratory failure, accounting for high morbidity and mortality. However, therapeutic approaches are rather limited. Targeting long non-coding RNA MALAT1 and microRNA miR-181a-5p might be potential option for ALI/ARDS intervention. Objective: We aimed to investigate the role of MALAT and miR-181a-5p in the pathogenesis of ALI/ARDS, and test the therapeutic effects of targeting MALAT and miR-181a-5p for ALI/ARDS intervention in vitro. Methods: MALAT1 and miR-181a-5p levels were measured in plasma from ALI/ARDS patients. In vitro human pulmonary microvascular endothelial cell (HPMEC) injury was induced by LPS treatment, and molecular targets of MALAT1 and miR-181a-5p were explored by molecular biology approaches, mainly focusing on cell apoptosis and vascular inflammation. Interaction between MALAT1 and miR-181a-5p was also detected. Finally, the effects of targeting MALAT1 and miR-181a-5p for ALI/ARDS intervention were validated in a rat ALI/ARDS model. Results: MALAT1 upregulation and miR-181a-5p downregulation were observed in ALI/ARDS patients. Transfection of mimic miR-181a-5p into HPMECs revealed decreased Fas and apoptosis, along with reduced inflammatory factors. Fas was proved to be a direct target of miR-181a-5p. Similar effects were also present upon MALAT1 knockdown. As for the interaction between MALAT1 and miR-181a-5p, MALAT1 knockdown increased miR-181a-5p expression. Knocking down of MALAT1 and miR-181a-5p could both improve the outcome in ALI/ ARDS rats. Conclusion: MALAT1 antagonism or miR-181a-5p could both be potential therapeutic strategies for ALI/ARDS. Mechanistically, miR-181a-5p directly inhibits Fas and apoptosis, along with reduced inflammation. MALAT1 negatively regulates miR-181a-5p.

MiR-181a-5p Delivered by Adipose-Derived Mesenchymal Stem Cell Exosomes Alleviates Klebsiella pneumonia Infection-Induced Lung Injury by Targeting STAT3 Signaling

“…Previous study showed that miR-181a-5p relieves inflammation by targeting endocan in monocrotaline-stimulated pulmonary arterial hypertension [29]. MiR-181a-5p regulates acute lung injury and respiratory distress syndrome [30]. MiR-181a-5p restricts vascular atherosclerosis and inflammation [31].…”

STAT3‐activated lncRNA XIST accelerates the inflammatory response and apoptosis of LPS‐induced acute lung injury

“…PMVECs (pulmonary microvascular endothelial cells) were administrated with lipopolysaccharide (LPS, 50 ng/mL, S1732‐25, Beyotime) to mimic the ALI cell model as previously reported. 11 …”

It isn t over ‘till it s over: A continuing concern of the SARS-CoV-2 variants, and miRNAs targeting the S protein as a probable absolute cure

“…miR-23a-3p has also been reported to have a potential of binding to IL-8 3'UTR [75]. miRNAs which are not present in MSCderived exosomes may also play critical roles in prognosis management [81]. For instance, miR-155 acts as a regulator of pro-inflammatory cytokines [82], and it also promotes innate immune responses of miR-155 and miR-128 against respiratory system viruses [83].…”