Inhibition of miR-21 ameliorates LPS-induced acute lung injury through increasing B cell lymphoma-2 expression

Ge, Junke; Yao, Yanfen; Jia, Haiyan; Li, Pibao; Sun, Wei

doi:10.1177/1753425920942574

Cited by 9 publications

(6 citation statements)

References 19 publications

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“…La participación de miR-21 en inflamación también presenta efectos notables en lesión pulmonar aguda, en donde se expresa de forma diferencial y se ha propuesto como blanco terapéutico, ya que se encontró que sus niveles plasmáticos, combinados con hallazgos ultrasónicos, se relacionan con el pronóstico de pacientes con esta condición, presentándose notablemente más elevado en aquellos con mayor mortalidad (28). En modelos murinos de esta lesión, la supresión de miR-21 atenuó la apoptosis inducida por lipopolisacáridos y promovió la supervivencia al proteger las células epiteliales pulmonares (29). En pacientes con trasplante de pulmón se observó una correlación entre la sobreexpresión de miR-21 y el proceso fibro-obliterativo de múltiples trastornos involucrados con fibrosis, entre ellos la disfunción crónica de aloinjerto pulmonar, enfermedad que limita la supervivencia de pacientes trasplantados.…”

Section: Enfermedades Pulmonaresunclassified

Aplicaciones clínicas de miR-21: revisión de la literatura

Gallardo-Sánchez,

Rivera-Cameras,

Morán-Moguel

et al. 2023

revbiomed

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hsa-micro RNA-21 (miR-21) es uno de los micro RNAs más estudiados debido al gran número de procesos en los que está involucrado y células en donde se expresa. Aunque la mayor parte de la investigación se ha dirigido a su papel en el cáncer, se ha encontrado que es un elemento regulador relevante en procesos fisiológicos y patológicos de virtualmente todos los sistemas. Esta revisión descriptiva resume la investigación más reciente realizada respecto a sus funciones biológicas y las potenciales aplicaciones clínicas como biomarcador y blanco terapéutico. Se realizó una búsqueda de “hsa-miR-21” en la base de datos de Pubmed y se seleccionaron los 50 artículos originales más recientes, con no más de cinco que se enfocaran en un solo sistema o área de especialidad. Esta revisión proporciona una visión general de las formas en que esta molécula influye la salud y los beneficios que su investigación podría proporcionar en el futuro para la supervivencia y calidad de vida de una variedad de pacientes.

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Section: Enfermedades Pulmonaresunclassified

Aplicaciones clínicas de miR-21: revisión de la literatura

Gallardo-Sánchez,

Rivera-Cameras,

Morán-Moguel

et al. 2023

revbiomed

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“…Beneficial effects on miR-21 expression inhibition have been observed with miR-21 antagomir in hypertrophic scarring of the skin 63 and inhibition of acute tissue injury in LPS-treated human pulmonary alveolar epithelial cells (HPAEpiC). 64 Even more, a personalized nanomedicine approach with functional nanoparticles was proposed to target both, miR-21 and target genes using the same therapeutic. 65 For the let-7, clinical trials are already ongoing for the evaluation of the therapeutic potential of this nc-RNA in various diseases such as obesity, diabetes, and cancer.…”

Section: Perspectivesmentioning

confidence: 99%

Non‐coding RNA and cholesteatoma

Jovanović

Živković

Jesić

et al. 2022

Laryngoscope Investig Oto

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Objective: Cholesteatoma is a challenging chronic pathology of the middle ear for which pharmacologic therapies have not been developed yet. Cholesteatoma occurrence depends on the interplay between genetic and environmental factors while master regulators orchestrating disease progression are still unknown. Therefore, in this review, we will discuss the diagnostic and therapeutic potential of non-coding RNAs (ncRNA) as a new class of regulatory molecules. Methods:We have comprehensively reviewed all articles investigating ncRNAs, specifically micro RNAs (miRNAs) and long ncRNAs (lncRNA/circRNA) in cholesteatoma tissue.Results: Candidate miRNA approaches indicated that miR-21 and let-7a are the major miRNAs involved in cholesteatoma growth, migration, proliferation, bone destruction, and apoptosis. Regulatory potential for the same biological processes was also observed for miR-203a. The NF-kB/miR-802/PTEN regulatory network was in relation to observed miR-21 activity in cholesteatoma as well. High throughput approaches revealed additional ncRNAs implicated in cholesteatoma pathology. Competitive endogenous RNA (ceRNA) analysis highlighted lncRNA/circRNA that could be "endogenous sponge" for miR-21 and let-7a based on the hypothesis that RNA transcripts can communicate with and regulate each other by using shared miRNA response elements. Conclusion:In this review, we summarize the discoveries and role of ncRNA in major pathways in cholesteatoma and highlight the potential of miRNA-based therapeutics in the treatment of cholesteatoma.

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“…The imbalance of the inflammatory response is considered a central theory in ALI, and miR-21-5p has been found to play a dual role in regulating this inflammatory response. In terms of pro-inflammatory effects, in LPS-induced ALI mouse models, miR-21-5p knockout has been shown to suppress the inflammatory response and promote mouse survival 18 , 19 . Conversely, in LPS-induced lung fibroblasts (WI-38) 20 , mouse lung microvascular endothelial cells (MPVECs) 21 , and human alveolar epithelial cells (HPAEpiC) 19 models, overexpression of miR-21-5p leads to an increase in the release of IL-6 and IL-1β.…”

Section: Introductionmentioning

confidence: 99%

MiR-21-5p modulates LPS-induced acute injury in alveolar epithelial cells by targeting SLC16A10

Zeng,

Zhou,

Liu

et al. 2024

Sci Rep

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Sepsis is a systemic inflammatory response syndrome resulting from the invasion of the human body by bacteria and other pathogenic microorganisms. 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 µg/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-1β), tumor necrosis factor-α (TNF-α) 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-1β and TNF-α 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-1β and TNF-α 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-1β and TNF-α mRNA and protein expression significantly increased at 6, 12, and 24 h after LPS stimulation as well as the miR-21-5p expression compared with the control group (P < 0.05). (2) After overexpression of miR-21-5p in A549 cells, the expression of IL-1β and TNF-α 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-1β and TNF-α in A549 cells after LPS treatment (P < 0.05). (5) miR-21-5p inhibitor increased the expression levels of IL-1β and TNF-α in A549 cells after LPS stimulation (P < 0.05). 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-1β and TNF-α (P < 0.05). 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.

show abstract

Inhibition of miR-21 ameliorates LPS-induced acute lung injury through increasing B cell lymphoma-2 expression

Cited by 9 publications

References 19 publications

Aplicaciones clínicas de miR-21: revisión de la literatura

Aplicaciones clínicas de miR-21: revisión de la literatura

Non‐coding RNA and cholesteatoma

MiR-21-5p modulates LPS-induced acute injury in alveolar epithelial cells by targeting SLC16A10

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