Involvement of lncRNAs and Macrophages: Potential Regulatory Link to Angiogenesis.
ABSTRACT: Macrophages are involved in angiogenesis, an essential process for organ growth and tissue repair, and could contribute to the pathogenesis of angiogenesis-related diseases such as malignant tumors and diabetic retinopathy. Recently, long noncoding RNAs (lncRNAs) have been proved to be important in cell differentiation, organismal development, and various diseases of pathological angiogenesis. Moreover, it has been indicated that numerous lncRNAs exhibit different functions in macrophage infiltration and polarization and regulate the secretion of inflammatory cytokines released by macrophages. Therefore, the focus of macrophage-related lncRNAs could be considered to be a potential method in therapeutic targeting angiogenesis-related diseases. This review mainly summarizes the roles played by lncRNAs which associated with macrophages in angiogenesis. The possible mechanisms of the regulatory link between lncRNAs and macrophages in various angiogenesis-related diseases were also discussed.
Project description:Long noncoding RNAs (lncRNAs) represent a large subgroup of RNAs that are longer than 200 nucleotides and have no apparent protein coding potential. They have diverse functions in different biological processes by regulating chromatin remodeling or protein translation. This review summarizes the recent progress of lncRNAs in angiogenesis and vascular diseases. A general overview of lncRNA functional mechanisms will be introduced. A list of lncRNAs, which are termed "Angio-LncRs", including MALAT1, MANTIS, PUNISHER, MEG3, MIAT, SENCR and GATA6-AS, will be discussed regarding their expression, regulation, function and mechanism of action in angiogenesis. Implications of lncRNAs in vascular diseases, such as atherosclerosis, hypertension, vascular retinopathies and tumor angiogenesis will also be discussed.
Project description:Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.
Project description:Accumulating studies indicate that long non-coding RNAs (lncRNAs) play important roles in the regulation of diverse biological processes involved in homeostatic control of the vessel wall in health and disease. However, our knowledge of the mechanisms by which lncRNAs control gene expression and cell signaling pathways is still nascent. Furthermore, only a handful of lncRNAs has been functionally evaluated in response to pathophysiological stimuli or in vascular disease states. For example, lncRNAs may regulate endothelial dysfunction by modulating endothelial cell proliferation (e.g. MALAT1, H19) or angiogenesis (e.g. MEG3, MANTIS). LncRNAs have also been implicated in modulating vascular smooth muscle cell (VSMC) phenotypes or vascular remodeling (e.g. ANRIL, SMILR, SENCR, MYOSLID). Finally, emerging studies have implicated lncRNAs in leukocytes activation (e.g. lincRNA-Cox2, linc00305, THRIL), macrophage polarization (e.g. GAS5), and cholesterol metabolism (e.g. LeXis). This review summarizes recent findings on the expression, mechanism, and function of lncRNAs implicated in a range of vascular disease states from mice to human subjects. An improved understanding of lncRNAs in vascular disease may provide new pathophysiological insights and opportunities for the generation of a new class of RNA-based biomarkers and therapeutic targets.
Project description:Pancreatic cancer (PC) is one of the most common causes of cancer-related death. The underlying mechanism of PC is not completely understood at present. Studies in recent years have demonstrated that long non-coding RNAs (lncRNAs) have multiple biological functions in cell growth, differentiation and proliferation. Notably, expressions of some lncRNAs undergo significant changes in the initiation and progression of cancers. In addition, lncRNAs are reported to be involved in various steps of PC development and have a potential value in the diagnosis, treatment and prognostic prediction of PC. In this review, we highlight recent evidence related to the molecular mechanism of lncRNAs in growth, survival, invasion, metastasis, angiogenesis and apoptosis of PC cells, and discuss the potential clinical application of lncRNAs to the diagnosis, treatment and prognostic prediction of PC.
Project description:A macrophage is an important component of innate immunity which can be activated by infection. A series of inflammatory cytokines are produced and released to eliminate pathogens. CpG DNA is an immune stimulator recognized by TLR9, subsequently inducing inflammatory responses in macrophages. Long noncoding RNA (lncRNA) is a novel class of noncoding RNA, whose length is more than 200?nt, but without protein-coding capacity. lncRNAs are involved in many physiological and pathological processes, including inflammatory responses. In our study, a lncRNA microarray assay was performed to identify differentially expressed lncRNAs and mRNAs in RAW264.7 cells at different time points following CpG ODN stimulation. The results revealed that expression levels of 734 lncRNAs and 734 mRNAs were altered at all time points. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses were performed to predict the functions of dysregulated genes. Coexpression networks of lncRNA-mRNA were constructed based on the correlation analysis between differentially expressed lncRNAs and 10 selected upregulated mRNAs, which have been reported to be involved in CpG DNA-induced inflammatory responses. In addition, we selected 8 dysregulated lncRNAs for further validation by quantitative real-time PCR. The present study provided a systematic perspective on the potential functions of lncRNAs in CpG ODN-induced macrophage activation.
Project description:Non-coding RNAs (ncRNAs) have been previously reported to serve an important role in transcription. In addition, several studies have revealed that long ncRNAs (lncRNAs) have a crucial role in human diseases. However, the association between lncRNAs and inflammation?induced intestinal macrophages in the intestinal mucosal barrier has remained elusive. In the present study, intestinal macrophages from healthy Sprague Dawley rats were divided into two groups: The experimental group, consisting of intestinal macrophages treated with 1 mg/l lipopolysaccharide (LPS) and the control group, composed of untreated cells. Differentially expressed (DE) lncRNAs and mRNAs between the control and experimental groups were identified using microarray profiling. The levels of DE mRNAs and lncRNAs were measured by reverse transcription?quantitative PCR (RT?qPCR). Furthermore, Gene Ontology (GO) and pathway enrichment analyses of DE mRNAs and lncRNAs were performed. To identify core regulatory factors among DE lncRNAs and mRNAs, a lncRNA?mRNA network was constructed. A total of 357 DE lncRNAs and 542 DE mRNAs between the LPS?treated and untreated groups were identified (fold-change >1.5; P<0.05). In addition, selected microarray data were confirmed by RT?qPCR. GO analysis of the DE mRNAs indicated that the biological functions of the upregulated mRNAs included inflammatory response, immune response, metabolic process and signal transduction, whereas those of the downregulated mRNAs were metabolic process, cell cycle, apoptosis and inflammatory response. In addition, pathway enrichment analysis of the upregulated mRNAs revealed that the most enriched pathways were the NF??B signaling pathway, B?cell receptor signaling pathway and apoptosis, while the downregulated mRNAs were significantly involved in metabolic pathways, the phosphatidylinositol signaling system, cytokine?cytokine receptor interaction and the Toll?like receptor signaling pathway. The lncRNA?mRNA co?expression network suggested that lncRNAs NONMMUT024673 and NONMMUT062258 may have an important role in LPS?induced intestinal macrophages. The present study identified the DE profiles between LPS? and non?LPS?treated intestinal macrophages. These DE lncRNAs and mRNAs may be used as potential targets for attenuating excessive inflammatory response in intestinal mucosal barrier dysfunction.
Project description:Liver disorders such as hepatitis, cirrhosis and hepatocellular carcinoma are a series of the most life threatening diseases along with extensive inflammatory cellular infiltrations. Macrophage has been proved to be key regulators and initiators of inflammation, and long non-coding RNAs (lncRNAs) are recommended to play critical roles in the occurrence and development of a variety of diseases. To uncover the role of macrophage in liver disorders via lncRNA sequencing method, we first applied a lncRNA classification pipeline to identify 1247 lncRNAs represented on the Affymetrix Mouse Genome 430/430A 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published gene expression profiles of silica particle exposed macrophages and liver respectively, and identified and validated sets of differentially expressed lncRNAs shared by macrophages and liver. The functional enrichment analysis of these lncRNAs was processed on the basis of their expression signatures, three aspects including cis, trans and co-acting proteins were proposed. This is the first time to correlate macrophage with liver disorders via co-expressed lncRNAs. Our findings indicated that roles of macrophage in liver disorders were double-edged, the differentially expressed lncRNAs and their corresponding regulatory genes or proteins may serve as potential diagnostic biomarkers and therapeutic targets.
Project description:Gastric cancer (GC) is the fourth most common malignant tumor. The mechanism underlying GC occurrence and development remains unclear. Previous studies have indicated that long non-coding RNAs (lncRNAs) are significantly associated with gastric cancer, but a systematic understanding of the role of lncRNAs in gastric cancer is lacking. In recent years, with the development of next-generation sequencing technology, tens of thousands of lncRNAs have been discovered. However, a large number of unannotated lncRNAs remain unidentified in different tissues, including potential gastric cancer-related lncRNAs. In this study, RNA sequencing (RNA-seq) data from 16 samples of eight gastric cancer patients were obtained and analyzed. A total of 1,854 previously unannotated lncRNAs were identified by ab initio assembly, and 520 differentially expressed lncRNAs were validated in the TCGA expression dataset. Methylation and copy number variation (CNV) array data from the same sample were integrated in the analysis. Changes in DNA methylation levels and CNVs may be responsible for the differential expression of 91 lncRNAs. Differentially expressed lncRNAs were enriched in coexpressed clusters of genes related to functions such as cell signaling, cell cycle, immune response, metabolic processes, angiogenesis, and regulation of retinoic acid (RA) receptors. Finally, a differentially expressed lncRNA, AC004510.3, was identified as a potential biomarker for the prediction of the overall survival of gastric cancer patients.
Project description:Atherosclerosis is characterized as a chronic inflammatory response to cholesterol deposition in arteries. Low-density lipoprotein (LDL), especially the oxidized form (ox-LDL), plays a crucial role in the occurrence and development of atherosclerosis by inducing endothelial cell (EC) dysfunction, attracting monocyte-derived macrophages, and promoting chronic inflammation. However, the mechanisms linking cholesterol accumulation with inflammation in macrophage foam cells are poorly understood. Long non-coding RNAs (lncRNAs) are a group of non-protein-coding RNAs longer than 200 nucleotides and are found to regulate the progress of atherosclerosis. Recently, many lncRNAs interfering with cholesterol deposition or inflammation were identified, which might help elucidate their underlying molecular mechanism or be used as novel therapeutic targets. In this review, we summarize and highlight the role of lncRNAs linking cholesterol (mainly ox-LDL) accumulation with inflammation in macrophages during the process of atherosclerosis.
Project description:Macrophages play an essential role in the immune system. Recent studies have shown that long non-coding RNAs (lncRNAs) can regulate genes encoding products involved in the immune response. Interleukin (IL)-27 is a member of the IL-6/IL-12 family of cytokines with broad anti-viral effects that inhibits human immunodeficiency virus (HIV) type-1 and herpes simplex virus (HSV). However, little is known about the role of lncRNAs in macrophages affected by IL-27. Therefore, we investigated the expression profiles of mRNA and lncRNA in human monocyte-derived macrophages (MDMs) regulated by IL-27. Monocytes were differentiated in the presence of macrophage-colony stimulatory factor (M-CSF)- or human AB serum with or without IL-27, and these cells were the subject for the profile analysis using RNA-Seq. We identified 146 lncRNAs (including 88 novel ones) and 434 coding genes were differentially regulated by IL-27 in both M-CSF- and AB serum-induced macrophages. Using weighted gene co-expression network analysis, we obtained four modules. The immune system, cell cycle, and regulation of complement cascade pathways were enriched in different modules. The network of mRNAs and lncRNAs in the pathways suggest that lncRNAs might regulate immune activity in macrophages. This study provides potential insight into the roles of lncRNA in macrophages regulated by IL-27.