An increase in a long noncoding RNA ANRIL in peripheral plasma is an indicator of stable angina.

INTRODUCTION: Stable angina develops during physical activity or stress, and it is typically an aspect of Coronary Heart Disease (CHD) that can lead to arrhythmia, heart failure and even sudden death. ANRIL, an Antisense Noncoding RNA gene in the INK4 Locus, is associated with multiple disorders including CHD; however, expressional levels of ANRIL in between patients with stable angina and myocardial infarction, one of the acute coronary syndrome, have not been clarified yet. METHODS: The authors enrolled 62 patients with myocardial infarction and 59 with stable angina before primary percutaneous coronary intervention, as well as 48 healthy volunteers. Their peripheral blood was collected for analysis of ANRIL and cardiac troponin I, a traditional diagnostic index of CHD by real-time PCR. RESULTS: The data showed that ANRIL is a better diagnostic indicator than cardiac troponin I in patients with stable angina and that the levels of ANRIL are higher in patients with stable angina than those with the myocardial infarction. DISCUSSION: The levels of ANRIL in peripheral plasma could be used as a good biomarker for stable angina.

Leverage of nuclease-deficient CasX for preventing pathological angiogenesis.

Gene editing with a CRISPR/Cas system is a novel potential strategy for treating human diseases. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) δ suppresses retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Here we show that an innovative system of adeno-associated virus (AAV)-mediated CRISPR/nuclease-deficient (d)CasX fused with the Krueppel-associated box (KRAB) domain is leveraged to block (81.2% ± 6.5%) in vitro expression of p110δ, the catalytic subunit of PI3Kδ, encoded by Pik3cd. This CRISPR/dCasX-KRAB (4, 269 bp) system is small enough to be fit into a single AAV vector. We then document that recombinant AAV serotype (rAAV)1 efficiently transduces vascular endothelial cells from pathologic retinal vessels, which show high expression of p110δ; furthermore, we demonstrate that blockade of retinal p110δ expression by intravitreally injected rAAV1-CRISPR/dCasX-KRAB targeting the Pik3cd promoter prevents (32.1% ± 5.3%) retinal p110δ expression as well as pathological retinal angiogenesis in a mouse model of oxygen-induced retinopathy. These data establish a strong foundation for treating pathological angiogenesis by AAV-mediated CRISPR interference with p110δ expression.

MACC1 as a Potential Target for the Treatment and Prevention of Breast Cancer.

Metastasis associated in colon cancer 1 (MACC1) is an oncogene first identified in colon cancer. MACC1 has been identified in more than 20 different types of solid cancers. It is a key prognostic biomarker in clinical practice and is involved in recurrence, metastasis, and survival in many types of human cancers. MACC1 is significantly associated with the primary tumor, lymph node metastasis, distant metastasis classification, and clinical staging in patients with breast cancer (BC), and MACC1 overexpression is associated with reduced recurrence-free survival (RFS) and worse overall survival (OS) in patients. In addition, MACC1 is involved in BC progression in multiple ways. MACC1 promotes the immune escape of BC cells by affecting the infiltration of immune cells in the tumor microenvironment. Since the FGD5AS1/miR-497/MACC1 axis inhibits the apoptotic pathway in radiation-resistant BC tissues and cell lines, the MACC1 gene may play an important role in BC resistance to radiation. Since MACC1 is involved in numerous biological processes inside and outside BC cells, it is a key player in the tumor microenvironment. Focusing on MACC1, this article briefly discusses its biological effects, emphasizes its molecular mechanisms and pathways of action, and describes its use in the treatment and prevention of breast cancer.

An increase in a long noncoding RNA ANRIL in peripheral plasma is an indicator of stable angina

Abstract Introduction: Stable angina develops during physical activity or stress, and it is typically an aspect of Coronary Heart Disease (CHD) that can lead to arrhythmia, heart failure and even sudden death. ANRIL, an Antisense Non-coding RNA gene in the INK4 Locus, is associated with multiple disorders including CHD; however, expressional levels of ANRIL in between patients with stable angina and myocardial infarction, one of the acute coronary syndrome, have not been clarified yet. Methods: The authors enrolled 62 patients with myocardial infarction and 59 with stable angina before primary percutaneous coronary intervention, as well as 48 healthy volunteers. Their peripheral blood was collected for analysis of ANRIL and cardiac troponin I, a traditional diagnostic index of CHD by real-time PCR. Results: The data showed that ANRIL is a better diagnostic indicator than cardiac troponin I in patients with stable angina and that the levels of ANRIL are higher in patients with stable angina than those with the myocardial infarction. Discussion: The levels of ANRIL in peripheral plasma could be used as a good biomarker for stable angina.

Network pharmacology study on the active components of Pterocypsela elata and the mechanism of their effect against cerebral ischemia.

OBJECTIVE: The aim of this study was to identify the active anti-ischemic components of Pterocypsela elata (P. elata) using a network pharmacology approach to construct an effective component anti-cerebral ischemic target network and systematically analyze this medicinal material. METHODS: Pharmacological studies have shown that P. elata has an obvious effect against cerebral ischemia. To identify the potential targets, 14 components of P. elata were docked to each structural element of the targets in the DRAR-CPI database by reverse docking technology. We then compared the identified potential targets with FDA-approved targets for stroke/cerebral infarction treatment in the DrugBank database and identified the active components of P. elata and their potential targets for stroke/cerebral infarction treatment. The active component-target networks were constructed using Cytoscape 3.5.1 software. The target protein-protein interactions were analyzed using the STRING database. KEGG pathway analysis and gene ontology (GO) enrichment analysis were performed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: There were 14 active components identified from P. elata and 21 potential targets identified for cerebral ischemia treatment, including carbonic anhydrase 2, ribosyldihydronicotinamide dehydrogenase, cholinesterase, and glutathione S-transferase P. The main involved pathways include metabolic pathways, complement and coagulation cascades and steroid hormone biosynthesis. CONCLUSION: Through a network pharmacology approach, we predicted the active components of P. elata and their potential targets for cerebral ischemia treatment. Our results provide new perspectives and clues for further studies on the anti-cerebral ischemia mechanism of P. elata.

Expression status and clinical significance of lncRNA APPAT in the progression of atherosclerosis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to modulate cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream were proposed to be potential biomarkers for clinical diagnosis. However, few cardiovascular diseases-related circulating lncRNAs were identified and their prediction power has not been investigated in depth. Here we report a new circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript (APPAT), and evaluated its role and predicting ability in atherosclerotic development. METHODS: APPAT was analyzed and screened by high-throughput sequencing, and then detected in vitro and in vivo. Immunofluorescence-fluorescence in situ hybridization (IF-FISH) was utilized to explore distribution and subcellular location of APPAT. The expressing alteration of APPAT in samples of healthy and pathological coronary artery was explored further. We also assessed the level of circulating APPAT in blood samples from healthy individuals, and patients with angina pectoris (AP) or myocardial infarction (MI). Additionally, we predicted and validated microRNA targets of APPAT, then showed the expression level of a candidate target which was primarily measured in human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined the potential indicating ability of APPAT for the risk of AP or MI. RESULTS: APPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It enriched in contractile VSMCs of artery tunica media and mainly existed in cytoplasm. Significant down-regulation of APPAT was found in coronary artery samples with severe stenosis. More importantly, we observed decreased expression of APPAT in blood samples accompanying disease progression. ROC and correlation analyses further verified the relatively high predicting ability of APPAT. We also observed the predicted miRNA exhibited opposite expression direction to that of APPAT. CONCLUSIONS: This study revealed that circulating lncRNA-APPAT may perform an important function and have some indicating ability on the development of atherosclerosis.

WDR26 promotes mitophagy of cardiomyocytes induced by hypoxia through Parkin translocation.

Myocardial ischemia is a heart condition caused by reduction of blood flow to the heart, preventing heart from receiving enough oxygen. Myocardial ischemia is the most common cause of death globally. Heart ischemic preconditioning (IPC) has a protective effect against myocardial cell death induced by ischemia and ischemia-reperfusion injury. WDR26 has recently been identified as a protein that is increased following rat cardiac IPC. WDR26 can promote the proliferation of H9c2 cells and protect cardiomyocytes against oxidative stress through inhibiting apoptosis. However, its role in myocardial ischemia is unclear. The aim of this study was to explore the role of WDR26 in myocardial ischemia and H9c2 cell hypoxia. Our results showed that WDR26 is induced by myocardial ischemia and H9c2 cell hypoxia. WDR26 protects H9c2 cells against hypoxia injury through inhibiting LDH release and increasing cell viability. WDR26 promotes hypoxia-induced autophagy in hypoxia of H9c2 cells. We further demonstrated that in H9c2 cell hypoxia, WDR26 increases mitochondrial membrane potential, thereby increases Parkin translocation of mitochondria. After Parkin is translocated at mitochondria, WDR26 can increase mitochondrial protein ubiquitination in hypoxia of H9c2 cells. WDR26 is a mediator of response to hypoxia, and WDR26 plays an important role in hypoxia-mediated autophagy and mitophagy. This study provides novel insights into the protective role of WDR26 in cardiomyocyte injury during hypoxia. WDR26 may serve as a potential target for the treatment of myocardial ischemia.

Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2.

The aberrant expression of microRNAs (miRNAs) is associated with colorectal carcinogenesis, but the underlying mechanisms are not clear. This study showed that the miRNA-27a (miR-27a) was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages-miR-27a was lower at stages III/IV than that at stage II. Bioinformatic and systemic biological analysis predicted several targets of miR-27a, among them SGPP1 and Smad2 were significantly affected. SGPP1 and Smad2 at mRNA and protein levels were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines. Increased miR-27a significantly repressed SGPP1 and Smad2 at transcriptional and translational levels. Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3. In vivo, miR-27a inhibited colon cancer cell growth in tumor-bearing mice. Taken together, this study has revealed miR-27a as a tumor suppressor and has identified SGPP1 and Smad2 as novel targets of miR-27a, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in colorectal cancer. Therefore, miR-27a could be a useful biomarker for monitoring colorectal cancer development and progression, and also could have a therapeutic potential by targeting SGPP1, Smad2 and STAT3 for colorectal cancer therapy.