MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD

Background/Aims: Previous studies revealed that circulating (either from plasma or serum) long non-coding RNA may predict the occurrence or prognosis of multiple human malignant tumors. In this study, we mainly explored whether circulating lncRNAs can be utilized as biomarkers predicting the development of human esophageal squamous cell carcinoma (ESCC). Methods: LncRNA microarray was applied to screen the potential biomarkers for ESCC. Each group contained three individual plasma samples. A multi-stage validation and risk score formula detection were used for validation. Results: Eleven dysregulated lncRNAs were obtained after Venny analysis. Further validation in a larger cohort including 205 ESCC patients, 82 patients suffering from esophagus dysplasia and 210 healthy controls confirmed that increased Linc00152, CFLAR-AS1 and POU3F3 might be potential biomarkers for predicting the early progress with an area under curve (AUC) of 0.698, 0.651 and 0.584, respectively. The merged AUC of the three factors and merged with CEA was 0.765 and 0.955, respectively. We also revealed that circulating levels of three lncRNAs were associated with poor post-surgery prognosis of ESCC patients. Conclusions: The three circulating lncRNAs might serve as potential biomarkers for predicting the early occurrence of ESCC.

Section: Introductionmentioning

confidence: 99%

Three Circulating LncRNA Predict Early Progress of Esophageal Squamous Cell Carcinoma

Zheng

2016

“…Myocytes injured during heart disease include both apoptotic and necrotic cells. Studies have shown that necrosis is more prominent in failing hearts and I/R hearts, which indicated that necrosis plays an important role in the pathological process of cardiac disease [11][12][13][14][15][16][17]. Oxidative stress is defined as an excess production of reactive oxygen species (ROS) relative to the endogenous antioxidant reserve to counteract the effects of ROS [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…Oxidative stress is defined as an excess production of reactive oxygen species (ROS) relative to the endogenous antioxidant reserve to counteract the effects of ROS [18][19][20][21][22]. Several studies have indicated that ROS induce the necrosis of cardiac myocytes and play a pivotal role in cardiac pathophysiology responsible for the development and progression of ischemic heart disease [17,23,24]. Nevertheless, the underlying mechanisms of cardiomyocyte necrotic death are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

Chen

Han

et al. 2016

Background/Aims: Cardiovascular disease is a growing major global public health problem. Necrosis is one of the main forms of cardiomyocyte death in heart disease. Oxidative stress is regarded as one of the key regulators of cardiac necrosis, which eventually leads to cardiovascular disease. Many pharmacological and in vitro studies have suggested that FGF-2 can act directly on cardiomyocytes to maintain the integrity and function of the myocardium and prevent damage during oxidative stress. However, the mechanisms by which FGF-2 rescues the myocardium from oxidative stress damage in cardiovascular disease remain unclear. The present study explored the protective effects of FGF-2 in the H₂O₂-induced necrosis of H9C2 cardiomyocytes as well as the possible signaling pathways involved. Methods: Necrosis of H9c2 cardiomyocytes was induced by H₂O₂ and assessed using a Cell Counting Kit-8 (CCK8) assay and flow cytometry analysis. The cells were pretreated with the PI3K/Akt inhibitor Wortmannin to investigate the possible involvement of the PI3K/Akt pathway in the protection by FGF-2. The levels of Akt, p-Akt, FoxO3a, p-FoxO3a, and BNIP3L were detected by Western blot. Chromatin immuno-precipitation (ChIP) analysis was used to test whether FoxO3a binds directly to the BNIP3L promoter region. A luciferase assay was used to study the effects of FoxO3a on BNIP3L gene promoter activity. Mitochondrial ΔΨM was quantified using tetramethylrhodamine methyl ester perchlorate (TMRM). The mitochondrial oxygen consumption rate (OCR) was assessed with a Seahorse XF24 Analyzer. Results: Treatment with H₂O₂ decreased the phosphorylation of Akt and FoxO3a, and it induced the nuclear localization of FoxO3a and the necrosis of H9c2 cells. These effects of H₂O₂ were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by the PI3K/Akt inhibitor Wortmannin. ChIP analyses indicated that FoxO3a binds directly to the BNIP3L promoter region. Using a luciferase assay, we further observed that FoxO3a increased BNIP3L gene promoter activity. As expected, overexpression of BNIP3L in H9C2 cardiomyoblast cells reduced the cardioprotection of FGF-2 in H₂O₂-induced necrosis and mitochondrial dysfunction. Conclusions: The present data suggest that FGF-2 protects against H₂O₂-induced necrosis of H9C2 cardiomyocytes via the activation of the PI3K/Akt/FoxO3a pathway. Moreover, the present results demonstrate that FoxO3a is an important transcription factor that acts by binding to the promoter and promoting the transcription of BNIP3L, and it contributes to the necrosis and mitochondrial dysfunction induced by H₂O₂ in H9c2 cardiomyoblast cells.

“…LncRNA NRF (Necrosis-Related Factor) was able to induce cardiomyocyte necrosis and exacerbate ischemia/reperfusion injury in H 2 O 2 -treated cardiomyocytes and myocardial infarction mice by sponging miR-873 and its target gene RIPK1 (Receptor-Interacting serine/threonine-Protein Kinase 1)/RIPK3 (Receptor-Interacting serine/threonine-Pro- [29].…”

Section: Nrf and H19 In Myocardial Necrosismentioning

confidence: 99%

Long Non-Coding RNAs in Cardiac Remodeling

Shen

Jiang

Bei

et al. 2017

Cardiac remodeling occurs after stress to the heart, manifested as pathological processes, including hypertrophy and apoptosis of cardiomyocytes, dysfunction of vascular endothelial cells and vascular smooth muscle cells as well as differentiation and proliferation of fibroblasts, ultimately resulting in progression of cardiovascular diseases. Emerging evidence has revealed that long non-coding RNAs (lncRNAs) acted as powerful and dynamic modifiers of cardiac remodeling. LncRNAs including Chaer, Chast, Mhrt, CHRF, ROR, H19, and MIAT have been implicated in cardiac hypertrophy while NRF, H19, APF, CARL, UCA, Mhrt and several other lncRNAs (n379599, n379519, n384640, n380433 and n410105) in cardiomyocyte loss and extracellular matrix remodeling. In addition, MALAT1 and TGFB2-OT1 have been reported to contribute to vascular endothelial cells dysfunction while lincRNA-p21 and lnc-Ang362 to vascular smooth muscle cells proliferation. Thus, manipulation of lncRNA expression levels through either the inhibition of disease-up-regulated lncRNAs or increasing disease-downregulated lncRNAs represents novel therapeutic strategies for cardiac remodeling.