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Long noncoding RNAs （LncRNAs）， a class of noncoding RNAs greater than 200 bases in length， are widely involved in the initiation， progression and glycolytic processes of many tumors， and can act as competitive endogenous RNA sponges to absorb miRNAs. LncRNAs can also inhibit miRNA expression， thereby regulate the glycolysis of tumor cells， affects cell proliferation， invasion and other biological activities. This review explores the roles of LncRNAs and glycolysis in digestive system tumors （DST）， a representative group of malignant tumors. Extending the LncRNA role in the diagnosis， treatment and prognosis of other tumors， we conclude that LncRNAs have the potential to be new candidate genes for tumorigenesis and serve as tumor biomarkers， which provides new insight into morbidity and mortality decrease of DST and other tumors.
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Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.
Subject(s)
Humans , Autoimmune Diseases/genetics , Epigenesis, Genetic , Lupus Erythematosus, Systemic/genetics , DNA Methylation , Psoriasis/geneticsABSTRACT
Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.
Subject(s)
Animals , Female , Humans , Male , Pregnancy , Environmental Exposure , Epigenesis, Genetic , Mammals/genetics , RNA, Small Untranslated/genetics , SpermatozoaABSTRACT
Occupational hand-arm vibration diseases(HAVD) is a legitimate occupational disease in China, and the mechanism of its pathogenesis is vibration-induced vascular injury. Once HAVD occurs, it is difficult for the patients to recover and can cause great harm to workers exposed to hand-arm vibration. It is difficult to detect and evaluate the occurrence and progress of the disease at an early stage using existing technology, which is disadvantageous to the early prevention and treatment of the disease. Long noncoding RNAs(lncRNAs) play an important role in regulating the development, growth, and remodeling of blood vessels and other biological processes. This article reviews the role and mechanism of lncRNAs in vascular injury, and provides scientific theoretical basis for early diagnosis and treatment of HAVD.
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Objetive: To detect the expressions of IncRNA H19 (H19) and IL-6/STAT3 pathway in the ulcerative colitis-associated colorectal cancer (CAC) tissue of the mice, and to explore its possible mechanism Methods: A total of 22 C57BL/6 mice were randomly divided into control group (n=10) and model group (n= 12). The CAC models were induced by azomethane (AOM) combined with dextran sodium sulfate (DSS) in the mice in model group. The mice were sacrificed on the 120th day, the disease activity index (DAI) of the mice was evaluated, the tumor formation rate was evaluated, the colon length was measured, and the pathomorphology of colon tissue of the mice was observed by HE staining. The serum IL-6 level of the mice was detected by ELISA. The expression levels of H19, let-7a, IL-6, STAT3 and c-Myc mRNA in colon tissue of the mice were detected by qPCR method. The expression levels of p-STAT3 and c-Myc proteins in colon tissue of the mice were detected by Western blotting method. Results: Compared with control group, the tumor formation rate of the mice in model group was 100%, the colon length was significantly shortened (P<0. 01), the DAI score was increased (P< 0.01), the colon tissue showed the intraepithelial neoplasia by HE staining, the expression levels of H19, IL-6, STAT3 and c-myc mRNA in colon tissue were significantly increased (P<0. 01), the expression level of let-7a mRNA in colon tissue was significantly decreased (P<0. 01), the serum IL-6 level was increased (P<0. 01), and the expression levels of p-STAT3 and c-Myc proteins in colon tissue were increased (P<0. 01). Conclusion: The pathogenesis of CAC in the mice may be related to the up-regulation of c-Myc and H19 and down-regulation of let-7a, which are mediated by IL-6/STAT3 pathway.
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Abstract Long-chain non-encoded RNAs (lncRNAs) are important in many life activities and can participate in the occurrence of hepatocellular carcinoma (HCC). Moreover, lncRNAs can be used as basis for developing new strategies to hinder liver cancer. To investigate the utility of lncRNAs in HCC as potential biomarkers for early detection and diagnosis, we mined genomic data from the Cancer Genome Atlas (TCGA), and analyzed the gene expressions from 374 tumor patients and 50 normal patients. The abnormal expressions of 387 differentially expressed lncRNAs (DElncRNAs) were identified from a total of 3099 lncRNAs. Moreover, 18 modules were divided based on WGCNA, and 2 of the 18 modules were positively correlated with stage and grade, and negatively correlated with survival time. Finally, 10 lncRNAs were found and their main functions are the enhancement of cellular metabolic capacity and cell proliferation. These 10 lncRNAs may serve as novel prognostic markers and therapeutic targets, and may help guide subsequent studies on HCC.
Subject(s)
Humans , Biomarkers, Tumor/genetics , Genetic Markers/genetics , Carcinoma, Hepatocellular/genetics , RNA, Long Noncoding/genetics , Liver Neoplasms/geneticsABSTRACT
Long noncoding RNAs (lncRNAs) are a class of RNAs that are more than 200 nucleotides in length with no protein coding property. LncRNAs are involved in almost every cellular process through multiple mechanisms. LncRNAs can directly bind to molecules in cells such as proteins, RNA, and DNA, to regulate cellular functions by influencing processes including transcription, translation, and molecular transporting. Recent researches showed lncRNAs are key regulators of serious cardiac diseases, especially in development and progression of cardiac ischemia, arrhythmia, cardiac fibrosis, and heart failure. This article mainly summarizes the function and mechanism of lncRNAs in cardiac diseases and gives reasonable prospect of lncRNAs in the future.
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Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.
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The problem of Keshan disease (KD) is confused with dilated cardiomyopathy (DCM) is still not solved.KD and DCM have different gene expression profiles,namely,different Micro RNAs (miRNAs) and Long noncoding RNAs (lncRNAs).There may be characteristic miRNAs and lncRNAs in KD and DCM.Systemically study differential gene expression profiles and regulation of noncoding RNAs gene expression and elucidate the different molecular pathogenesis in gene expression and gene expression regulation will provide theoretic basis in identification,prevention and treatment of KD and DCM.
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Long noncoding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. Most lncRNAs have pro-nounced oncogenic effects associated with tumorigenesis and progression, promoting the proliferation, migration, invasion, and me-tastasis of tumor cells. The specific lncRNAs expression in particular types of cancers makes them promising diagnostic and prognostic biomarkers. Currently, studies on lncRNAs expression, functions, and mechanisms have attracted considerable attention in cancer re-search. However, these studies mainly focus on epitheliogenic malignant tumors. In this review, we outline the current state of infor-mation on lncRNAs and research progress on its role in haematopoietic and lymphoid tissue tumors.
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Objective To study the effect of long non-coding RNAs (lncRNAs) maternally imprinted genes 3 (MEG3) on human abortion vilii development and to explore the related molecular mechanisms. Methods We collected the vilii samples from 15 spontaneous abortion (SA) and 15 induced abortion (IA) patients. Immunohistochemistry was applied to detect the expressions of apoptosis factor Bax and apoptosis inhibitory factor Bcl-2 in vilii samples. Real-time quantitative polymerase chain reaction (qPCR) was used to analyze the levels of MEG3 of vilii samples. Overexpression of MEG3 in human trophoblast cell line HTR-8/SVneo was identified by qPCR; the invasion ability of HTR-8/SVneo cells was examined by matrigel invasion assay in MEG3 overexpression and control groups. Results Immunohistochemistry showed that the expression of Bax in IA group was lower than that in SA group, while the expression of Bcl-2 was higher (P<0.01). The level of MEG3 in IA group was significantly higher than that in SA group (P<0.01). The expression of MEG3 was obviously increased and invasion ability was inhibited in MEG3 overexpressed HTR-8/SVneo cells (P<0.01). Conclusion LncRNAs MEG3 may regulate the apoptosis and invasive ability of bizarre trophoblastic cells and influence on the development of human villi.
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Long noncoding RNAs (lncRNAs) are non-protein coding transcript larger than 200 nucleotides,making up a large fraction of cellular transcripts in mammalian.Recent years have seen a surge of studies aimed at functionally characterizing the role of lncRNAs in development and disease.It has been proved that this kind of noncoding RNAs regulate gene expression at epigenetic,transcriptional,and post-transcriptional levels.Retinal development is dependent on an accurately functioning network of transcriptional and translational regulators.Among the diverse classes of molecules involved,lncRNAs play a significant role.LncRNAs are known or suspected to play a functional role in the specification and maturation of retinal cell subtypes and involved in several ocular related diseases.Though the molecular mechanism of most lncRNAs is still largely unclear,it is likely that these molecules represent a major component involved in retinal cell fate determination.In the process of retinal development,lncRNAs could induce cell differentiation,affect cell cycle and regulate X chromosome inactivation.lncRNAs also play an important role in ocular diseases,such as anophthalmia,diabetic retinopathy and spinocerebellar movement disorder type 7.This manuscript reviewed recent advances in the role of lncRNAs in retinal development and ocular diseases,and the existing problems,which is of great significance for basic and clinical research and the development of new therapeutic target.
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Non-coding RNAs mainly include microRNAs and long non-coding RNAs (LncRNAs),which work as a kind of RNA to regulate the expression of gene at the levels of transcription,post-transcription and epigenetics.Recent studies have shown that many non-coding RNAs are dysregulated during liver regeneration after partial hepatectomy.This review summarized the biological characteristics and regulatory mechanisms of non-coding RNAs in liver regeneration after partial hepatectomy.
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[Summary] Long noncoding RNA( lncRNA) plays an important role in regulating the life activities, and its disordered expression is closely related to many diseases. Several studies have shown that lncRNA could modulate the endocrine metabolic processes at transcription, post-transcription, and the epigenetic modification levels, but the exact mechanism is still unclear. Further research needs to be done. This review will briefly describe the research progress of lncRNAs in endocrine and metabolic respects.
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Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets.
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Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The exploration of new biomarkers with high sensitivity and specificity for early diagnosis of AMI therefore becomes one of the primary task. In the current study, we aim to detect whether there is any heart specific long noncoding RNA (lncRNA) releasing into the circulation during AMI, and explore its function in the neonatal rat cardiac myocytes injury induced by H2O2. Our results revealed that the cardiac-specific lncRNA MHRT (Myosin Heavy Chain Associated RNA Transcripts) was significantly elevated in the blood from AMI patients compared with the healthy control (*p<0.05). Using an in vitro neonatal rat cardiac myocytes injury model, we demonstrated that lncRNA MHRT was upregulated in the cardiac myocytes after treatment with hydrogen peroxide (H2O2) via real-time RT-PCR (qRT-PCR). Furthermore, we knockdowned the MHRT gene by siRNA to confirm its roles in the H2O2-induced cardiac cell apoptosis, and found that knockdown of MHRT led to significant more apoptotic cells than the non-target control (**p<0.01), indicating that the lncRNA MHRT is a protective factor for cardiomyocyte and the plasma concentration of MHRT may serve as a biomarker for myocardial infarction diagnosis in humans AMI.
Subject(s)
Animals , Humans , Rats , Apoptosis , Biomarkers , Diagnosis , Early Diagnosis , Heart , Hydrogen Peroxide , Mortality , Myocardial Infarction , Myocytes, Cardiac , Plasma , RNA , RNA, Long Noncoding , RNA, Small Interfering , Sensitivity and SpecificityABSTRACT
Long noncoding RNAs( lncRNAs) are classified as transcripts >200 nucleotides in length with lit-tle or no evidence of protein-coding potential, and can regulate gene expression at various levels, including transcriptional regulation, posttranscriptional processing and so on.It has been widely involved in cell differentiation, individual develop-ment and other important life processes.Recent studies show lncRNA-related dysfunction plays critical roles in various dis-eases, indicating that lncRNA may serve as a new target for disease diagnosis and treatment.This review summarizes the functions of lncRNAs, including various modes of lncRNAs in regulating gene expression, the roles of lncRNAs in differen-tiation and development, and the connection between lncRNAs and malignant tumor.
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It was previously revealed that noncoding RNAs, especially microRNAs, control cardiac genes and regulate heart function.Recently, growing evidence from high-throughput genomic platforms has confirmed that long non-coding RNAs ( lncRNAs) serve as new and enigmatic regulators in cardiac development and homeostasis.Nevertheless, lit-tle is known about their characteristics compared to microRNAs.Here, we review the latest progress on lncRNAs in cardiac biology and diseases, summarizing detailed knowledge of their functions and novel cardiac-related gene regulatory mecha-nisms in epigenetic processes.Finally, we highlight that lncRNAs could be promising therapeutic targets and diagnostic bi-omarkers in cardiac pathophysiology.
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Long non-coding RNAs are RNA transcripts longer than 200 nt without any function of coding protein,and gradually become a new focus of cancer research because of their important roles in regulating genes expression at the epigenetic,transcriptional and post-transcriptional levels.Recently,more researches show that are closely related to the occurrence of breast cancer and other tumors.Therefore,in this review,we summarize the developing understanding of LncRNAs associated with breast cancer.
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Studies have shown that most of the sequence in the mammalian genome is transcribed into long noncoding RNAs (lncRNAs). Their crucial roles in gene regulation are becoming a hotspot in current biomedical research. LncRNAs can control gene activities through multiple mechanisms such as: 1) direct or indirect regulation of gene expression via cis-/trans-action or function as protein baits in the nucleus; 2) affecting the stability and the translational process of mRNA; 3) functioning as competitors to regulation of microRNA; 4) binding to transcription factors. Recent studies have highlighted the significance of lncRNAs in development and diseases, and their potentials in future clinical application.