刘剑扬
阜外华中心血管病医院 大血管外科
MicroRNAs (miRNAs/miRs) function as key regulators in breast cancer (BC). The present study aimed to verify the function and molecular regulation of miR-337-3p in BC cells. Bioinformatics analysis was performed to screen key genes and miRNAs associated with BC. Reverse transcription-quantitative PCR and western blot analyses were performed to detect RNA and protein expression levels. Cell Counting Kit-8, BrdU and cell adhesion assays, and flow cytometric analysis were performed to assess the biological behaviors of BC cells. The dual-luciferase reporter, RNA pull-down assays, and Pearson's correlation analysis were performed to determine the association between miRNAs and mRNAs. Bioinformatics analysis revealed that miR-337-3p and cyclin-dependent kinase 1 (CDK1) acted as key regulators in BC. In addition, miR-337-3p was expressed at low levels in BC cells and tissues, which suppressed BC progression. CDK1 expression was upregulated in BC cells and tissues, which was associated with increased cell proliferation and adhesion, as well as decreased apoptosis in BC. Notably, miR-337-3p targeted CDK1 to inhibit BC cell progression. Taken together, the results of the present study suggest that miR-337-3p plays a tumor-suppressive role in BC by targeting CDK1.
Oncology letters 2022
BACKGROUND:Herein, we aimed to analyze cardiac metabolic reprogramming in patients with tetralogy of Fallot (ToF).METHODS:Cardiac metabolic reprogramming was analyzed through comprehensive bioinformatics analysis, which included gene set enrichment, gene set variation, and consensus clustering analyses, so as to assess changes in metabolic pathways. In addition, full-spectrum metabolomics analysis was performed using right atrial biopsy samples obtained from patients with ToF and atrial septal defect (ASD) before cardiopulmonary bypass; ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to construct a metabolic map of cardiac metabolic reprogramming in cyanotic congenital heart disease.RESULTS:The metabolic maps of carbohydrate metabolic process and heme metabolism were significantly activated, while bile acid metabolism, lipid droplet, and lipid binding were primarily restrained in ToF samples as compared with that in ASD samples. The reprogramming of butanoate metabolism was identified basing on the UPLC-MS/MS detection and analysis in myocardial hypoxia damage in cyanotic heart disease. Finally, the butanoate metabolism-related hub regulators ALDH5A1 and EHHADH were identified and they were significantly downregulated in ToF samples.CONCLUSIONS:The metabolic network of butanoate metabolism involved ALDH5A1 and EHHADH, which could contribute to myocardial tissue damage in cyanotic congenital heart of ToF. Our results provide further insights into the mechanisms underlying metabolic reprogramming in cyanotic congenital heart disease and could lead to the identification of potential therapeutic targets.
Frontiers in pediatrics 2021
This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient (ApoE-/-) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.
Molecules and cells 2019
