CircRbms1 fosters MST1 mRNA and protein levels to motivate myocardial ischaemia-reperfusion injury via autophagic status.

AIMS: Acute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia-reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury. METHODS AND RESULTS: An in vivo MI mice model and an in vitro MI cell model was established. The expression levels were detected using quantitative real-time PCR (qRT-PCR) and western blot. Cellular proliferation, apoptosis, pyroptosis, and autophagy were detected by immunostaining, immunohistochemistry, western blot, and transmission electron microscopy (TEM). Dual-luciferase reporter assay, RNA pull-down assay, and RIP assay were performed to validate the molecular interactions. CircRbms1 was up-regulated in A/R-induced HCMs and acted as a sponge for miR-142-3p, thereby targeting MST1. CircRbms1 could improve stability of MST1 by recruiting IGF2BP2 (all P < 0.05). CircRbms1 knockout reduced cell pyroptosis, improved autophagy and proliferation level in A/R-induced HCMs (all P < 0.05). CircRbms1 knockout alleviated cardiac dysfunction and cell pyroptosis and enhanced autophagy and proliferation in mice through the miR-142-3p/MST1 axis. CONCLUSIONS: CircRbms1 inhibited the miR-142-3p/MST1 axis and played a protective role in myocardial I/R injury. It may provide a new therapeutic target for I/R heart injury.

LncRNA RNA ROR Aggravates Hypoxia/Reoxygenation-Induced Cardiomyocyte Ferroptosis by Targeting miR-769-5p/CBX7 Axis.

Ferroptosis is a new way of cell death which is reported to participate in the pathology of myocardial ischemia-reperfusion (MI/R) injury, but it's mechanism remains unclear. The present investigation is to study the emerging role of long non-coding RNA (lncRNA) regulator of reprogramming (ROR) in cardiomyocyte ferroptosis after hypoxia/reoxygenation (H/R) administration. RT-qPCR and/or Western blot methods were performed to examine the gene/or protein levels, and CCK-8, ELISA, and DCFH-DA staining determined the cellular viability and ferroptosis. Dual-luciferase and RNA immunoprecipitation were applied to verify molecular interaction. LncRNA ROR and miR-769-5p were overexpressed and reduced in blood samples from MI patients and H/R-treated AC16 cells, respectively. Mechanistically, lncROR sponged to miR-769-5p, thus upregulating CBX7 expression. Functional experiments presented that lncRNA ROR silence mitigated H/R-stimulated inflammatory damage, oxidative stress, and ferroptosis in AC16 cells, whereas these roles could be reversed by co-downregulation of miR-769-5p or co-overexpression of CBX7. These data uncovered that lncRNA ROR prevented against H/R-induced cardiomyocyte ferroptosis by modulating miR-769-5p/CBX7 signaling, emphasizing the therapeutic value of lncRNA ROR in MI/R injury.

Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy.

Immune checkpoint inhibitors (ICIs) significantly improve the survival of patients with non-small-cell lung cancer (NSCLC), but only some patients obtain clinical benefits. Predictive biomarkers for ICIs can accurately identify people who will benefit from immunotherapy. Lipid metabolism signaling plays a key role in the tumor microenvironment (TME) and immunotherapy. Hence, we aimed to explore the association between the mutation status of the lipid metabolism pathway and the prognosis of patients with NSCLC treated with ICIs. We downloaded the mutation data and clinical data of a cohort of patients with NSCLC who received ICIs. Univariate and multivariate Cox regression models were used to analyze the association between the mutation status of the lipid metabolism signaling and the prognosis of NSCLC receiving ICIs. Additionally, The Cancer Genome Atlas (TCGA)-NSCLC cohort was used to explore the relationships between the different mutation statuses of lipid metabolism pathways and the TME. Additionally, we found that patients with high numbers of mutations in the lipid metabolism pathway had significantly enriched macrophages (M0- and M1-type), CD4 + T cells (activated memory), CD8 + T cells, Tfh cells and gamma delta T cells, significantly increased expression of inflammatory genes [interferon-γ (IFNG), CD8A, GZMA, GZMB, CXCL9, and CXCL10] and enhanced immunogenic factors [neoantigen loads (NALs), tumor mutation burden (TMB), and DNA damage repair pathways]. In the local-NSCLC cohort, we found that the group with a high number of mutations had a significantly higher tumor mutation burden (TMB) and PD-L1 expression. High mutation status in the lipid metabolism pathway is associated with significantly prolonged progression-free survival (PFS) in NSCLC, indicating that this marker can be used as a predictive indicator for patients with NSCLC receiving ICIs.