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One of its most prevalent complications is acute lung injury, which places a significant medical burden on numerous countries and regions due to its high morbidity and mortality rates. MicroRNA (miRNA) plays a critical role in the body's inflammatory response and immune regulation. Recent studies have focused on miR-21-5p in the context of acute lung injury, but its role appears to vary in different models of this condition. In the LPS-induced acute injury model of A549 cells, there is differential expression, but the specific mechanism remains unclear. Therefore, our aim is to investigate the changes in the expression of miR-21-5p and SLC16A10 in a type II alveolar epithelial cell injury model induced by LPS and explore the therapeutic effects of their targeted regulation. A549 cells were directly stimulated with 10\u00a0\u00b5g\/ml of LPS to construct a model of LPS-induced cell injury. Cells were collected at different time points and the expression of interleukin 1 beta (IL-1\u03b2), tumor necrosis factor-\u03b1 (TNF-\u03b1) and miR-21-5p were measured by RT-qPCR and western blot. Then miR-21-5p mimic transfection was used to up-regulate the expression of miR-21-5p in A549 cells and the expression of IL-1\u03b2 and TNF-\u03b1 in each group of cells was measured by RT-qPCR and western blot. The miRDB, TargetScan, miRWalk, Starbase, Tarbase and miR Tarbase databases were used to predict the miR-21-5p target genes and simultaneously, the DisGeNet database was used to search the sepsis-related gene groups. The intersection of the two groups was taken as the core gene. Luciferase reporter assay further verified SLC16A10 as the core gene with miR-21-5p. The expression of miR-21-5p and SLC16A10 were regulated by transfection or inhibitors in A549 cells with or without LPS stimulation. And then the expression of IL-1\u03b2 and TNF-\u03b1 in A549 cells was tested by RT-qPCR and western blot in different groups, clarifying the role of miR-21-5p-SLC16A10 axis in LPS-induced inflammatory injury in A549 cells. (1) IL-1\u03b2 and TNF-\u03b1 mRNA and protein expression significantly increased at 6, 12, and 24\u00a0h after LPS stimulation as well as the miR-21-5p expression compared with the control group (P\u2009&lt;\u20090.05). (2) After overexpression of miR-21-5p in A549 cells, the expression of IL-1\u03b2 and TNF-\u03b1 was significantly reduced after LPS stimulation, suggesting that miR-21-5p has a protection against LPS-induced injury. (3) The core gene set, comprising 51 target genes of miR-21-5p intersecting with the 1448 sepsis-related genes, was identified. This set includes SLC16A10, TNPO1, STAT3, PIK3R1, and FASLG. Following a literature review, SLC16A10 was selected as the ultimate target gene. Dual luciferase assay results confirmed that SLC16A10 is indeed a target gene of miR-21-5p. (4) Knocking down SLC16A10 expression by siRNA significantly reduced the expression of IL-1\u03b2 and TNF-\u03b1 in A549 cells after LPS treatment (P\u2009&lt;\u20090.05). (5) miR-21-5p inhibitor increased the expression levels of IL-1\u03b2 and TNF-\u03b1 in A549 cells after LPS stimulation (P\u2009&lt;\u20090.05). In comparison to cells solely transfected with miR-21-5p inhibitor, co-transfection of miR-21-5p inhibitor and si-SLC6A10 significantly reduced the expression of IL-1\u03b2 and TNF-\u03b1 (P\u2009&lt;\u20090.05). MiR-21-5p plays a protective role in LPS-induced acute inflammatory injury of A549 cells. By targeting SLC16A10, it effectively mitigates the inflammatory response in A549 cells induced by LPS. Furthermore, SLC16A10 holds promise as a potential target for the treatment of acute lung injury.<\/jats:p>","DOI":"10.1038\/s41598-024-61777-x","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T17:02:05Z","timestamp":1715792525000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["MiR-21-5p modulates LPS-induced acute injury in alveolar epithelial cells by targeting SLC16A10"],"prefix":"10.1038","volume":"14","author":[{"given":"Huanan","family":"Zeng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2629-7386","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"61777_CR1","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","volume":"193","author":"C Fleischmann","year":"2016","unstructured":"Fleischmann, C. et al. 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