ABSTRACT
Myocardial fibrosis is a common pathological feature in various advanced cardiovascular diseases, and progressive fibrosis is the pathological basis for the development and progression of many cardiac arrhythmias and heart failure. There are no effective reversal drugs for myocardial fibrosis, which is related to the lack of understanding of the molecular mechanisms. Noncoding RNAs are a class of RNAs that do not function as coding proteins, and have been found to be intimately involved in the life cycle of cardiomyocyte differentiation, transcription and apoptosis, and are important regulators of cardiovascular diseases. An increasing number of studies have shown that noncoding RNAs regulate the proliferation and transformation of cardiac fibroblasts through related signaling pathways and can be used as potential biomarkers and novel therapeutic targets for cardiac fibrosis. This article reviews the relationship between noncoding RNAs and cardiac fibrosis.
ABSTRACT
With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.
Subject(s)
Humans , Open Reading Frames , Peptides , Glucose , Genome , Metabolic DiseasesABSTRACT
Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.
Subject(s)
Humans , RNA, Untranslated/genetics , RNA , Myocardial Infarction/genetics , Biomarkers , Computational Biology , MicroRNAs/geneticsABSTRACT
Chemotherapy is one of the important methods to treat cancer, and the emergence of multidrug resistance (MDR) is one major cause for the failure of cancer chemotherapy. Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients, reducing their effects on killing cancer cells. Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with a complex process of multiple genes, factors, pathways, and multiple steps, and today the MDR-associated mechanisms are largely unknown. In this paper, from the aspects of protein-protein interactions, alternative splicing (AS) in pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance in cell functions, and influence from the tumor microenvironment, we summarize the molecular mechanisms associated with MDR in cancers. In the end, prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties, biocompatibility, availability, and other advantages.
ABSTRACT
Non-coding RNA (ncRNA) used to be considered as a class of gene transcripts without protein-coding capacity. Whereas emerging evidence has demonstrated that a small fraction of ncRNAs are still capable of producing functional peptides. Such ncRNAs and corresponding peptides are highly conserved and homologous, and can be detected by sequencing or mass spectrometry analysis. In this paper, we searched several databases with the keywords of "non-coding RNA" and "peptide", and briefly reviewed the characteristics of ncRNA that can be translated into functional small peptides, detection methods of peptides, biological functions of peptides and clinical application value of peptides. The results show that these functional peptides are often involved in disease processes, such as regulation of tumor progression, muscle activity and immune disorders. NcRNA-encoded peptides can be used as novel and efficacious disease diagnostic, therapeutic, and prognostic tools, and further develop as anticancer therapeutic targets to provide new ideas for individual precise treatment of tumors.
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Bacterial non-coding RNAs (ncRNAs) are pivotal transcriptional regulators during bacterial proliferation and infection processes.Bacterial ncRNAs play important roles in responding to environmental changes and regulating bacterial gene expression to resist environmental stress.Transcriptome profiling of neonatal meningitis-causing Escherichia coli K1 RS218 (NMEC) reveals abundant ncRNAs.Bioinformatic analyses identified 45 potential ncRNAs.Comparative genome analyses of non-pathogenic E.coli K12 and NMEC identified 300 NMEC-specific sequences (above 100 bp), which contain 9 NMEC-specific ncRNAs (Nsr).Moreover, deletion of one ncRNA, Nsr21, enhanced NMEC survival and proliferation in mouse blood (P< 0.01) , compared to the wild-type RS218 control, in a mouse tail vein injection model.qRT-PCR analysis further revealed expression of Nsr21 decreased in NMEC collected from mouse blood compared to that in NMEC collected from in vitro medium (P<0.001) , indicating that NMEC downregulates Nsr21 expression to benefit its survival and proliferation in blood.This study suggests that the NMEC genome contains a number of ncRNAs, which may be involved in regulating NMEC pathogenicity.During infection process in the blood, NMEC enhances its proliferation ability in blood by downregulating the expression of Nsr21.
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Alzheimer ' s disease (AD ) , an age-associated chronic progressive neurodegeneration disorder, is characterized by progressive loss of memory, cognitive impairment and behavioral changes.The pathological hallmarks of AD are (3-amyloid (A(3) deposition, neurofibrillary tangles induced by phosphorylation of tau protein, upregulation of inflammation and neuronal apoptosis.Amyloid is a polypeptide consisting of 39-42 amino acids which is produced by a series of enzymatic hydrolysis of amyloid precursor protein in neurons.Studying the regulation of the production and clearance of Ais of great importance which may help in finding potential intervention to effectively delay or even reverse the process of Alzheimer's disease.As the key enzyme of A(3 production, (3-secretase ((3-site APP cleaving enzyme 1, BACE'l) plays an essential role in the development of AD.The aggregation of inflammatory cells around senile plaques suggests that A(3 is highly associated with neuroinflammation.Neuroinflammation-related cells participate in the clearance of A(3 and multiple cytokines regulate the level of A0.In addition, although non-coding UNA is rarely involved in the production, deposition and clearance of A(3 directly, it can regulate the production of A(3 through other pathways.In this article, we will focus on the important role of BACE1, neuroinflammation and non-coding RNA in the regulation of A(3 and review the mechanism of production and clearance of A(3 in AD.
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BACKGROUND: The antisense noncoding mitochondrial RNAs (ASncmtRNAs) derive from the mitochondrial 16S gene. Knockdown of these transcripts with chemically-modified antisense oligonucleotides induces proliferative arrest, apoptosis and invasiveness reduction in tumor but not normal cells. One of these transcripts, ASncmtRNA-2, contains the complete and identical sequence of hsa-miR-4485-3p and, upon knockdown of this transcript, there is a strong increase in levels of this miRNA, suggesting ASncmtRNA-2 as a source for miR-4485-3p, which is supported by several evidences from our group and others, in the ex vivo setting. RESULTS: Here we show that incubation of in vitro-transcribed ASncmtRNA-2 with recombinant Dicer produces RNA fragments corresponding to hsa-miR-4485-3p, showing that Dicer binds to and processes ASncmtRNA-2, strongly supporting the hypothesis that ASncmtRNA-2 acts as a precursor for miR-4485-3p. CONCLUSION: The in vitro results presented here strengthen the hypothesis that miR-4485-3p is derived from ASncmtRNA-2 by Dicer processing. Since miR-4485-3p is classified as a tumor suppressor miRNA, this evidence strengthens the application of ASncmtRNA knockdown for cancer therapy.
Subject(s)
MicroRNAs/genetics , RNA, Long Noncoding/genetics , Gene Expression Regulation, Neoplastic , RNA, Antisense/genetics , Cell Line, Tumor , Cell Proliferation , RNA, Mitochondrial/geneticsABSTRACT
Postmortem interval （PMI） estimation has always been an important and difficult issue in the field of forensic pathology. In recent years, research progress on the estimation of PMI using RNA specific variation patterns after death has been made by researchers at home and aboard. This paper summarizes the specific application methods of messenger RNA and non-coding RNA for PMI estimation based on the literatures and discusses the existing problems and development trends, in order to provide technical reference for related studies and estimation practice.
Subject(s)
Humans , Autopsy , Forensic Pathology , Postmortem Changes , RNA, Messenger/genetics , RNA, Untranslated , Time FactorsABSTRACT
Non-coding RNA (ncRNA), expressed widely in organisms and comprised of a complex, regulatory and controlling biologically network, is an emerging theme in the biomedicine field at present. Regulatory sncRNAs, for example, microRNA (miRNA), endogenous small interfering RNA (siRNA) and PIWI-interacting RNA (piRNA), are the key members of the gene regulatory network and play important roles in the regulation of multiple pathophysiological activities in cells. Male infertility, a serious social problem all over the world, is mainly related the malfunctions of the spermatogenesis caused by known or unknown factors; and finally result in azoospermia, oligozoospermia or asthenospermia. Recent research indicated that regulatory sncRNAs play important roles in the development, differentiation and mature of the germ cells and their functions at different stages by silencing the transposable elements and regulating the expression of coding gene; and their abnormal expression in germ cells at different stage is closely related to male infertility. In this review, the roles and recent progresses of regulatory sncRNA focusing on piRNA to provide insight for future research in this field and for the diagnoses, interventions and treatments of male infertility are briefly summarized.
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@#Objective: To detect the expression of non-coding RNA snord105b in gastric cancer (GC) tissues, sera and cell lines, and its correlation with clinicopathological characteristics of patients with GC as well as its effect on the proliferation of GC cells. Methods: One hundred and twenty pairs of GC tissues and corresponding para-cancerous tissues from patients, who underwent surgery at Department of Surgery, the Fourth Hospital of Hebei Medical University between 2016 and 2017, were collected for this study. The presurgical sera samples from GC patients (n=50) and peripheral venous blood samples from healthy donors (n=30), as well as five gastric cancer cell lines (SGC-7901, AGS, MGC-803, BGC-823, HGC-27) and gastric mucosa normal epithelial GES-1 cells were also obtained. qPCR assay was adopted to detect the expression of snord105b in GC tissues, sera and cell lines. The correlation between snord105b and patients’clinicopathological features was investigated. MTS assay was adopted to detect the effect of snord105b silence or over-expressionon in vitro proliferation of four GC cells. Results: qPCR assay demonstrated that the expression of snord105b in GC tissues, sera and cell lines were significantly higher than that of para-cancerous tissues, sera from healthy donors and GES-1 cells (all P< 0.05). Expression level of snord105b was obviously associated with age,tumor size, differentiation and TNM stages of patients (all P<0.05). MTS assay demonstrated that knockdown of snord105b could suppress the proliferation of GC cells (P< 0.05), while forced-expression of snord105b could promote the proliferation of GC cells (P< 0.05). Conclusion: non-coding RNA snord105b aberrantly expressed in GC tissues, sera, and cells, and its expression was obviously correlated with patients’age, tumor size, differentiation and TNM stages. Snord105b could significantly promote the proliferation of GC cells, which may be used as a potential clinical biomaker for early diagnosis and prognosis of GC.
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With the development of whole genome and transcrip-tome sequencing technologies, a growing body of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) has been i-dentified and is receiving increasing attention. LncRNAs and circRNAs are non-protein encoding transcripts whose functions are crucial for advancing our comprehensive understanding of bi-ological processes in human health and diseases, specifically tumor. And there is a close relationship between circRNAs and lncRNAs in their origin and function. In this paper, we have re-viewed the recent advances of lncRNAs and circRNAs in tumor by focusing on their relationships, which may help to distinguish them and identify tumor biomarkers further.
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Mental disorders are caused by the synergy of genetic and environmental factors,and epigenetics provides a bridge for mental disorders between environmental exposure and genetic background.This review discussed the role of epigenetics on the development of mental disorders,especially in schizophrenia and depression.DNA methylation,histone acetylation,histone methylation,ncRNA,depressive disorder and schizophrenia were used as searching terms.('Schizophrenia OR depressive disorder') and all field of DNA methylation/histone acetylation/histone methylation/ncRNA were taken as index strategy.67 related articles in database of PubMed,ScienceDirect in March 2017 were acquired.41 articles were enrolled as reviewing materials according to literature screening.Existing researches suggest that epigenetic modifications,including DNA methylation,histone acetylation,histone methylation,and ncRNAs,may be associated with the occurrence of mental illnesses and play key roles in the pathogenesis of mental illnesses,especially in schizophrenia and depression.Further studies on them could provide us novel insights into the pathogenesis of these disorders and effective treatments based upon epigenetic mechanisms.
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Circular RNA ( circRNA) , a novel type of endogenous non-coding RNA ( ncRNA) , has been broadly taken into account during recent years as a research hot-spot.Unlike linear RNA, circRNA form covalently closed loop structure by jointing 3′and 5′ends together via exon circularization or intron circularization.Through which way it is more stable and conserved than linear RNA.Besides, circRNAs are abundant and multiple existences in creatures have been revealed.Nowadays, an increasing number of researchers have found that circRNA plays an essential role in the regulation of gene expression, which has broadened the view of di-verse endogenous noncoding RNA, and therefore hints that circRNA has great potential in clinical diagnosis and treatment of disease. In this paper, we make an overview of the latest research about circRNAs from the aspects of generation, character, function, and the relationship with diseases, and so on.
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A subset of mammalian genes differ functionally between two alleles due to genomic imprinting, and seven such genes (Peg3, Usp29, APeg3, Zfp264, Zim1, Zim2, Zim3) are localized within the 500-kb genomic interval of the human and mouse genomes, constituting the Peg3 imprinted domain. This Peg3 domain shares several features with the other imprinted domains, including an evolutionarily conserved domain structure, along with transcriptional co-regulation through shared cis regulatory elements, as well as functional roles in controlling fetal growth rates and maternal-caring behaviors. The Peg3 domain also displays some unique features, including YY1-mediated regulation of transcription and imprinting; conversion and adaptation of several protein-coding members as ncRNA genes during evolution; and its close connection to human cancers through the potential tumor suppressor functions of Peg3 and Usp29. In this review, we summarize and discuss these features of the Peg3 domain.