ABSTRACT
AIM: Endothelial cell injury assumes a fundamental part in the pathogenesis of atherosclerosis, and endothelial cell autophagy has protective effects on the development of atherosclerosis, although the underlying molecular regulation mechanism is indistinct. This study aimed to investigate whether microRNA-214-3p (miR-214-3p) is involved in the endothelial cell autophagy regulation of atherosclerosis. METHODS: We utilized ApoE-/- mice provided with a high-fat diet (HFD) as atherosclerosis model. We analysed the level of miR-214-3p and the levels of autophagy-related protein 5 (ATG5) and autophagy-related protein 12 (ATG12) in the purified CD31+ endothelial cells from mouse aorta. Bioinformatics analysis and a dual-luciferase reporter assay were performed to confirm the binding target of miR-214-3p. In vitro study, human umbilical vein endothelial cells (HUVECs) were transfected with miR-214-3p mimics/inhibitor and stimulated with 100 µg/mL oxidized low-density lipoprotein (ox-LDL) for 12 hours to initiate a stress-repairing autophagic process. RESULTS: In mouse models, we identified an inverse correlation between miR-214-3p, ATG5 and ATG12. We observed that in young HUVECs, ox-LDL-initiated autophagy was repressed by miR-214-3p overexpression, as evaluated by autophagic protein analysis, microtubule-associated protein 1 light chain 3B-II (LC3B-II) immunofluorescence assay and transmission electron microscopy (TEM). Also, miR-214-3p promoted ox-LDL accumulation in HUVECs and THP-1 monocyte adhesion. Conversely, in old HUVECs, suppression of miR-214-3p preserved the ability to initiate a protective autophagy reaction to the ox-LDL stimulation. CONCLUSION: miR-214-3p regulates ox-LDL-initiated autophagy in HUVECs by directly targeting the 3'UTR of ATG5 and may have a suitable role in the pathogenesis of atherosclerosis.
Subject(s)
Atherosclerosis/metabolism , Autophagy/physiology , Endothelial Cells/pathology , MicroRNAs/metabolism , Animals , Autophagy/drug effects , Diet, High-Fat , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Lipoproteins, LDL/pharmacology , Mice , Mice, KnockoutABSTRACT
Background and aim. Long non-coding RNAs (lncRNAs) have been demonstrated to act as a critical regulator in the processes of tumor biology. In this study, whether lncRNA-ATB is a potential indicator for non-small cell lung cancer (NSCLC) was investigated and its biological function in NSCLC was also determined. Methods. The expression levels of lncRNA-ATB in NSCLC tissues and cell lines were measured. A549 cell line was explored to investigate the functions of lncRNA-ATB in NSCLC. Results. Real-time PCR results showed that lncRNA-ATB expression was up-regulated in both in NSCLC tissues and cell lines. High lncRNA-ATB expression in tumor tissue was associated with larger tumor size, lymph node metastasis, and distant metastasis in patients with NSCLC, respectively. In addition, the patients with high expression of lncRNA-ATB presented a lower survival probability. In vitro experiments showed that down-regulation of lncRNA-ATB promoted the cell apoptosis, whereas inhibited the cell viability, cell migration, and cell invasion. Conclusion. High expression of lncRNA-ATB indicated a poor prognosis and led to the cell proliferation and metastasis in NSCLC (AU)
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Subject(s)
Humans , Male , Female , Carcinoma, Non-Small-Cell Lung/diagnosis , Neoplasm Metastasis/diagnosis , Cell Proliferation , RNA, Long Noncoding/analysis , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Prognosis , Cell Line , Cell Line/radiation effects , Transfection/trends , Neoplasm Metastasis/pathology , Carcinoma, Non-Small-Cell Lung/complications , Flow Cytometry , Cellular Apoptosis Susceptibility Protein/analysis , RNA/genetics , Biomarkers, Tumor/analysisABSTRACT
BACKGROUND AND AIM: Long non-coding RNAs (lncRNAs) have been demonstrated to act as a critical regulator in the processes of tumor biology. In this study, whether lncRNA-ATB is a potential indicator for non-small cell lung cancer (NSCLC) was investigated and its biological function in NSCLC was also determined. METHODS: The expression levels of lncRNA-ATB in NSCLC tissues and cell lines were measured. A549 cell line was explored to investigate the functions of lncRNA-ATB in NSCLC. RESULTS: Real-time PCR results showed that lncRNA-ATB expression was up-regulated in both in NSCLC tissues and cell lines. High lncRNA-ATB expression in tumor tissue was associated with larger tumor size, lymph node metastasis, and distant metastasis in patients with NSCLC, respectively. In addition, the patients with high expression of lncRNA-ATB presented a lower survival probability. In vitro experiments showed that down-regulation of lncRNA-ATB promoted the cell apoptosis, whereas inhibited the cell viability, cell migration, and cell invasion. CONCLUSION: High expression of lncRNA-ATB indicated a poor prognosis and led to the cell proliferation and metastasis in NSCLC.
