胡延磊
阜外华中心血管病医院 心血管外科
PURPOSE:Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI).METHODS:A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosis-related genes were measured.RESULTS:The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2.CONCLUSIONS:It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.
Acta cirurgica brasileira 2023
AIMS:As a severe cardiovascular disease, acute myocardial infarction (AMI) could trigger congestive heart failure. Periostin (Postn) has been elucidated to be dramatically up-regulated in myocardial infarction. Abundant expression of Postn was also observed in the infarct border of human and mouse hearts with AMI. This work is dedicated to explore the mechanism through which Postn exerts its functions on AMI.METHODS AND RESULTS:The expression of Postn in AMI mice and hypoxia-treated neonatal mouse cardiomyocytes (NMCMs) was quantified by qRT-PCR. The biological functions of Postn in AMI were explored by trypan blue, TUNEL, flow cytometry analysis, and JC-1 assays. Luciferase activity or MS2-RIP or RNA pull-down assay was performed to study the interaction between genes. Postn exhibited up-regulated expression in AMI mice and hypoxia-treated NMCMs. Functional assays indicated that cell apoptosis in NMCMs was promoted via the treatment of hypoxia. And Postn shortage could alleviate cell apoptosis in hypoxia-induced NMCMs. Postn was verified to bind to mmu-miR-203-3p and be down-regulated by miR-203-3p overexpression. Postn and miR-203-3p were spotted to coexist with small nucleolar RNA host gene 8 (Snhg8) in RNA-induced silencing complex. The affinity between Snhg8 and miR-203-3p was confirmed. Afterwards, Snhg8 was validated to promote cell apoptosis in hypoxia-induced NMCMs partially dependent on Postn. Furthermore, vascular endothelial growth factor A (Vegfa) was revealed to bind to miR-203-3p and be implicated in the Snhg8-mediated AML cell apoptosis and angiogenesis.CONCLUSIONS:miR-203-3p availability is antagonized by Snhg8 for Postn and Vegfa-induced AMI progression.
ESC heart failure 2022
INTRODUCTION:Sepsis represents a life-threatening disease caused by a series of infections, which may be complicated with severe myocardial depression (MD). Long noncoding RNAs (lncRNAs) are closely related to sepsis-induced myocardial depression (SIMD). This study aimed to seek out the mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in the growth of SIMD.METHODS:Venous blood samples were collected from 62 patients with sepsis; the sepsis rat model was established with 15 mg/kg lipopolysaccharide (LPS), and the H9C2 cardiomyocyte injury model was established with 1 μg/mL LPS. In the rat and cardiomyocyte models, MIAT was inhibited. The expression of MIAT in normal tissues and SIMD tissues was detected. Then, the functional assays of MIAT were performed in rats and H9C2 cells for detection of cardiac function, hemodynamics, inflammation response, myocardial function, oxidative stress, tissue stainings, and cardiomyocyte viability and apoptosis. Western blot analysis was used to measure the levels of apoptosis-related proteins and the nuclear factor kappa B (NF-κB) axis-related proteins.RESULTS:MIAT was highly expressed in SIMD patients. Silencing MIAT alleviated inflammation and apoptosis and improved myocardial function in SIMD rats by downregulating the NF-κB axis. In LPS-induced H9C2 cardiomyocytes, silencing MIAT alleviated inflammation and oxidative stress and inhibited apoptosis by downregulating the NF-κB axis, thus mitigating cardiomyocyte injury.CONCLUSIONS:MIAT could assist the diagnosis of SIMD and might affect the progression of SIMD by regulating the NF-κB pathway.
The Journal of surgical research 2022
Coronary heart disease (CHD) is one of the most vital reasons for death and disability all over the world. miRNA, as a plasma index, is quite valuable for disease screening and prognosis prediction in CHD. Mining the molecular mechanism behind miRNA is also helpful for us to find molecular therapeutic strategies. In this research, we found that the expression of plasma miR-30c-5p in CHD patients was obviously lower than that in the control group (CG), which had a high differential value for CHD. We also discovered that miR-30c-5p was obviously correlated with clinical characteristics of CHD patients such as age, NYHA grade, smoking history, hypertension, hyperlipidemia, etc. In prognosis analysis, the miR-30c-5p expression in patients with poor prognosis was dramatically lower than that in those with good one, and the AUC for predicting poor prognosis of CHD was not lower than 0.850. In addition, we also induced myocardial ischemia/reperfusion (I/R) injury model of H9C2 cells through hypoxia/reoxygenation, and found that H9C2 cells also had abnormally down-regulated miR-30c-5p and up-regulated BCL2-like 11 (BCL2L11). Up-regulating miR-30c-5p or down-regulating BCL2L11 were helpful to improve proliferation and apoptosis of I/R injury model. Mechanically, BCL2L11 was also negatively regulated by miR-30c-5p, and up-regulating the former could cancel the in vitro protective effect of up-regulating the latter on H9C2 cell I/R injury model. In vivo research, up-regulating miR-30c-5p or down-regulating BCL2L11 can improve myocardial injury, histopathological changes and apoptosis in rat I/R model.
American journal of translational research 2021
BACKGROUND:Non-small cell lung cancer (NSCLC) is a heterogeneous tumor that accounts for approximately 85% of all lung cancer cases worldwide. microRNAs (miRNAs) are believed to play an important role in regulating a variety of biological processes, including immunity and cancer. We investigated the effect of miR-519d-3p on the mitigation of NSCLC in vitro and in vivo.METHODS:RT-PCR or immunohistochemical assays were used to assess the expression of miR-519d-3p. Colony formation, flow cytometry, and transwell assay were respectively used to detect proliferation, apoptosis, and invasion of A549 and NCI-H661 cell lines. Luciferase reporter assay was used to verify targeting the relationship between mir-519d-3p and VEGFA. Western blot was used to examine the expression of Ki67, caspase-3, E-cadherin, N-cadherin, VEGF, P38, and PI3K/AKT. Animal models were established by BABL/c mice to research the effect of mir-519d-3p overexpression in vivo.RESULTS:In vitro, miR-519d-3p overexpression inhibited A549 and NCI-H661 cells proliferation, invasion, and also promoted apoptosis. In addition, miR-519d-3p overexpression downregulated VEGFA expression and decreased the P38 and PI3K/AKT phosphorylation level. In vivo, miR-519d-3p overexpression significantly restrained tumor volume (2087±265 mm3 vs 599±135 mm3, *P< 0.05) and tumor weight (0.45±0.08 g vs 0.13±0.06 g, *P<0.05) compared with the control group. Overexpression of miR-519d-3p downregulated levels of Ki67 and N-cadherin significantly.CONCLUSION:The data indicated that miR-519d-3p could be a novel therapy or adjuvant against NSCLC.
OncoTargets and therapy 2020
