miR-26a-5p protects against myocardial ischemia/reperfusion injury by regulating the PTEN/PI3K/AKT signaling pathway

Xing, Xiaowei; Guo, Shuang; Zhang, Guanghao; Liu, Yusheng; Bi, Shao‐Jie; Wang, Xin; Lu, Qinghua

doi:10.1590/1414-431x20199106

Cited by 75 publications

(48 citation statements)

References 28 publications

(34 reference statements)

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“…MiR-26a-5p expression was observed inversely correlated with IL-6 tissue expression, one of the cytokines directly regulated by this miRNA ( 28 ). IL-6 is an important biomarker for the severity of COVID-19, supporting our correlation results in the COVID-19 lung biopsies and others studies describing its association with endothelial activation/dysfunction and inflammatory vascular responses ( 29 , 30 ). The second miRNA selected, miR-29b-3p, was also shown to be associated with an immune and adaptive response ( 31 ).…”

Section: Discussionsupporting

confidence: 91%

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

Centa

Fonseca

Ferreira

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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MicroRNAs (miRNAs) are critical modulators of endothelial homeostasis, which highlights their involvement in vascular diseases, including the ones caused by virus infections. Our main objective was to identify miRNAs involved in the endothelial function and determine their expression in post-mortem lung biopsies of COVID-19 patients with severe respiratory injuries and thrombotic events. Based on functional enrichment analysis, miR-26a-5p, miR-29b-3p, and miR-34a-5p were identified as regulators of mRNA targets involved in endothelial, and inflammatory signaling pathways as well as in viral diseases. A miRNA/mRNA network, constructed based on protein-protein interactions of the miRNA targets and the inflammatory biomarkers characterized in the patients, revealed a close interconnection of these miRNAs with relevance to the endothelial activation/dysfunction. Reduced expression levels of selected miRNAs were observed in the lung biopsies of COVID-19 patients (n=9) compared to the Controls (n=10)(P<0.01-0.0001). MiR-26a-5p and miR-29b-3p presented the best power to discriminate these groups (AUC=0.8286, and AUC=0.8125, respectively). The correlation analysis of the miRNAs with inflammatory biomarkers in the COVID-19 patients was significant for miR-26a-5p [IL-6 (r2=0.5414), and ICAM-1(r2=0.5624)], and miR-29b-3p [IL-4 (r2=0.8332), and IL-8 (r2=0.2654)]. Altogether, these findings demonstrate the relevance and the non-random involvement of miR-26a-5p, miR-29b-3p, and miR-34a-5p in endothelial dysfunction and inflammatory response in patients with SARS-CoV-2 infection and the occurrence of severe lung injury and immunothrombosis.

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Section: Discussionsupporting

confidence: 91%

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

Centa

Fonseca

Ferreira

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Similarly, in the present study, we found that PTEN not only inhibited the migration and invasion, and induced apoptosis of EC cells, but also reversed the effect of miR-25-3p on EC cells, which further confirmed that miR-25-3p regulated the migration, invasion, and apoptosis of EC cells by targeting PTEN. It's also well known that the activity of PTEN antagonizes the PI3K/AKT pathway to suppress cancer cell survival, which means that deficient PTEN expression leads to the PI3K/AKT pathway activation, thereby enhancing cell anti-apoptosis [ 33–35 ]. In investigating the down-stream mechanism of miR-25-3p mediated in EC in the present study, we also observed that enhanced PTEN expression suppressed the activation of the PI3K/AKT pathway, and miR-25-3p-induced decrease of PTEN expression further enhanced the PI3K/AKT pathway activation, while overexpression of PTEN could inhibit the effect of miR-25-3p on this pathway.…”

Section: Discussionmentioning

confidence: 99%

MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway

et al. 2020

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Background: Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system. MiR-25-3p was proved to be a biomarker for the diagnosis and treatment of many cancers. MiR-25-3p was found to be high expressed in the blood of EC patients. The aim of this study was to explore the effect of miR-25-3p and its target gene on EC. Methods: miR-25-3p expression in the blood of EC patients and EC cells was detected by RT-qPCR. The target of miR-25-3p was identified by bioinformatics and luciferase reporter assay. After transfection, cell viability, apoptosis, migration and invasion were detected by MTT, flow cytometry, wound healing and transwell assays, respectively. The expressions of PTEN, Bax, Bcl-2, cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blot. Results: MiR-25-3p was high expressed in the blood of EC patients and EC cells. MiR-25-3p targeted PTEN and inhibited the expression of PTEN. MiR-25-3p mimic increased the viability, migration, invasion and the expressions of Bcl-2 and Cleaved caspase-3, and inhibited the apoptosis and the expression of Bax in EC cells. MiR-25-3p mimic also enhanced the expressions of p-PI3K and p-AKT and the ratios of p-PI3K/PI3K and p-AKT/AKT in EC cells. PTEN overexpression not only had an opposite effect of miR-25-3p mimic, but also reversed the effect of miR-25-3p mimic on EC cells. Conclusion: MiR-25-3p targeted PTEN to promote the migration and invasion, and inhibit apoptosis of EC cells via the PI3K/AKT pathway, which might provide a new therapeutic target for EC treatment.

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“…For instance, Wei et al (22) have reported that miR-26a-5p overexpression could improve cerebral ischemia/reperfusion injury via attenuating cell apoptosis. Xing et al (23) have indicated that miR-26a-5p could protect against myocardial ischemia/reperfusion injury by modulating the PTEN/PI3K/AKT pathway. However, the function of miR-26a-5p in LPS-induced ALI is unclear.…”

Section: Discussionmentioning

confidence: 99%

miR‑26a‑5p alleviates lipopolysaccharide‑induced acute lung injury by targeting the connective tissue growth factor

Yang

Fei

2020

Mol Med Rep

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The aim of the present study was to investigate the regulatory functions of microRNA (miR)-26a-5p on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its molecular mechanisms. The role of miR-26a-5p on an ALI mouse model was evaluated by examining the histological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) expression levels in lung tissues and the survival of ALI mice. Moreover, the protein concentration and the number of neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) was analyzed. To explore the effect of miR-26a-5p on inflammatory responses and apoptosis, the expression levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 and apoptosis were measured by ELISA, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling staining and flow cytometry in BALF, A549 cells and lung tissues. B-cell lymphoma-2 (Bcl-2), Bax and cleaved caspase-3 in lung tissues were measured by western blotting and reverse transcription-quantitative PCR. Connective tissue growth factor (CTGF) was predicted as a direct target of miR-26a-5p using dual luciferase reporter assay. The present study sought to determine whether CTGF overexpression reversed the effect of miR-26a-5p on apoptosis and inflammatory responses in LPS-induced A549 cells. The data revealed that miR-26a-5p overexpression ameliorated LPS-induced ALI, which was implicated by fewer histopathological changes, W/D ratio, apoptosis in lung tissues and the survival of ALI mice. Moreover, miR-26a-5p overexpression alleviated LPS-induced inflammatory responses in ALI mice via the reduction of total protein, neutrophil and lymphocyte counts and the expression levels of TNF-α, IL-1β, IL-6, MDA and MPO activity in BALF. Similarly, miR-26a-5p overexpression decreased apoptosis and the expression of TNF-α, IL-1β and IL-6 in LPS-induced A549 cells. CTGF was a direct target of miR-26a-5p. CTGF overexpression reversed the effect of miR-26a-5p on cell apoptosis and inflammatory responses in LPS-induced A549 cells. The present study demonstrated that miR-26a-5p could attenuate lung inflammation and apoptosis in LPS-induced ALI by targeting CTGF.

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miR-26a-5p protects against myocardial ischemia/reperfusion injury by regulating the PTEN/PI3K/AKT signaling pathway

Cited by 75 publications

References 28 publications

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway

miR‑26a‑5p alleviates lipopolysaccharide‑induced acute lung injury by targeting the connective tissue growth factor

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