Dataset Information

Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts.

ABSTRACT: Ischemic preconditioning (IPre) reduces ischemia/reperfusion (I/R) injury in the heart. The non-coding microRNA miR-125b-1-3p has been demonstrated to play a role in the mechanism of IPre. Hypercholesterolemia is known to attenuate the cardioprotective effect of preconditioning; nevertheless, the exact underlying mechanisms are not clear. Here we investigated, whether hypercholesterolemia influences the induction of miR-125b-1-3p by IPre. Male Wistar rats were fed with a rodent chow supplemented with 2% cholesterol and 0.25% sodium-cholate hydrate for 8 weeks to induce high blood cholesterol levels. The hearts of normo- and hypercholesterolemic animals were then isolated and perfused according to Langendorff, and were subjected to 35 min global ischemia and 120 min reperfusion with or without IPre (3 × 5 min I/R cycles applied before index ischemia). IPre significantly reduced infarct size in the hearts of normocholesterolemic rats; however, IPre was ineffective in the hearts of hypercholesterolemic animals. Similarly, miR-125b-1-3p was upregulated by IPre in hearts of normocholesterolemic rats, while in the hearts of hypercholesterolemic animals IPre failed to increase miR-125b-1-3p significantly. Phosphorylation of cardiac Akt, ERK, and STAT3 was not significantly different in any of the groups at the end of reperfusion. Based on these results we propose here that hypercholesterolemia attenuates the upregulation of miR-125b-1-3p by IPre, which seems to be associated with the loss of cardioprotection.

SUBMITTER: Szabo MR

PROVIDER: S-EPMC7312064 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts.

Szabó Márton R MR Gáspár Renáta R Pipicz Márton M Zsindely Nóra N Diószegi Petra P Sárközy Márta M Bodai László L Csont Tamás T

International journal of molecular sciences 20200526 11

Ischemic preconditioning (IPre) reduces ischemia/reperfusion (I/R) injury in the heart. The non-coding microRNA miR-125b-1-3p has been demonstrated to play a role in the mechanism of IPre. Hypercholesterolemia is known to attenuate the cardioprotective effect of preconditioning; nevertheless, the exact underlying mechanisms are not clear. Here we investigated, whether hypercholesterolemia influences the induction of miR-125b-1-3p by IPre. Male Wistar rats were fed with a rodent chow supplemented ...[more]

PMID: 32466450

Similar Datasets

Project description:ObjectivePeriodontitis is a chronic inflammatory infectious disease caused by the deposition of dental plaque on the tooth surface, leading to adverse systemic consequences. Accumulating evidence shows that dysregulated microRNAs (miRNAs) are associated with the disease severity of periodontitis. Herein, we report two novel miRNAs, miR-30b-3p and miR-125b-1-3p, in the context of periodontitis and their relationships with disease severity of periodontitis.MethodsThe miRNA profiles of gingival crevicular fluid (GCF) samples were used to screen differentially expressed miRNAs (DEmiRNAs) between periodontitis patients and periodontally healthy individuals. Clinical human GCF samples were collected from 80 patients diagnosed with periodontitis (PD +) for the first time and 100 periodontally healthy individuals (PD-). The severity of periodontitis was categorized into mild/moderate (MPD) and severe (SPD) groups. The expressions of miR-30b-3p and miR-125b-1-3p were determined by quantitative real-time PCR. The levels of IL-1β, IL-6, and TNF-α were determined by ELISA methods.ResultsWe applied GEO2R bioinformatics tool to analyze the raw data of the GSE89081 dataset and identified miR-30b-3p (|logFC|= 1.987) and miR-125b-1-3p (|logFC|= 1.878) between periodontitis patients and periodontally healthy individuals. It was found that PPD, CAL, BOP, and the relative expression levels of miR-30b-3p and miR-125b-1-3p were all higher in the PD + group than the PD- group, in the SPD group than the MPD group (P < 0.05). The periodontitis patients with high-miR-30b-3p expression exhibited increased PPD, CAL, and BOP compared to those low-miR-30b-3p expression, while high-miR-125b-1-3p expression group showed significant differences on PPD and BOP from low-miR-125b-1-3p expression group (P < 0.05). Pearson correlation analysis demonstrated a significantly positive correlation between the levels of inflammatory cytokines, miR-30b-3p expression, and miR-125b-1-3p expression (P < 0.001). Results of ROC curves showed AUC of 0.878 and 0.927, sensitivity of 0.843 and 0.855, and specificity of 0.791 and 0.801, respectively, when miR-30b-3p and miR-125b-1-3p expression levels were used to diagnose periodontitis.ConclusionThese data unveiled that miR-30b-3p and miR-125b-1-3p expressions may be associated with the pathogenesis of periodontitis.

Project description:Colon cancer is one of the most prevalent malignancies that lead to high occurrence of cancer-related deaths. Currently, chemotherapies and radiotherapies remain the primary treatments for advanced colon cancer. Despite the initial effectiveness, a fraction of colon cancer patients developed cisplatin resistance, resulting in therapeutic failure. The long non-coding RNA differentiation antagonizing non-coding RNA (DANCR) has been shown to be upregulated in multiple cancers, indicating an oncogenic role of DANCR. This study aims to elucidate the roles of DANCR in regulating cisplatin (CDDP) resistance of colon cancer. We found DANCR was significantly upregulated in colon cancer tissues and cells compared with normal colon tissues and cells. DANCR was upregulated in cisplatin-resistant colon cancer cells. Moreover, overexpression of DANCR significantly desensitized colon cancer cells to cisplatin. On the other way, silencing DANCR dramatically overrode CDDP resistance of colon cancer cells. Bioinformatics prediction revealed DANCR could bind to seeding region of miR-125b-5p as a competitive endogenous RNA. This interference was further validated by luciferase assay. Moreover, we detected a negative correlation between DANCR and miR-125b-5p in colon cancer patient tissues: miR-125b-5p was clearly downregulated in colon cancer tissues and cells. Overexpression of miR-125b-5p significantly sensitized cisplatin-resistant cells. Interestingly, we observed the cisplatin-resistant cells were associated with a significantly increased glycolysis rate. We further identified glycolysis enzyme, hexokinase 2 (HK2), as a direct target of miR-125b-5p in colon cancer cells. Rescue experiments showed overexpression of miR-125b-5p suppressed cellular glycolysis rate and increased cisplatin sensitivity through direct targeting the 3' UTR of HK2. Importantly, silencing endogenous DANCR significantly induced the miR-125b-5p/HK2 axis, resulting in suppression of the glycolysis rate and increase in cisplatin sensitivity of colon cancer cell. Expectedly, these processes could be further rescued by inhibiting miR-125b-5p in the DANCR-silenced cells. Finally, we validated the DANCR-promoted cisplatin resistance via the miR-125b-5p/HK2 axis from an in vivo xenograft mice model. In summary, our study reveals a new mechanism of the DANCR-promoted cisplatin resistance, presenting the lncRNA-DANCR-miR-125b-5p/HK2 axis as a potential target for treating chemoresistant colon cancer.

Project description:BackgroundAmorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described.ResultsWe first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation.ConclusionsOur findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products.

Dataset Information

Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts.

Publications

Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets