The role of long non-coding RNAs in genome formatting and expression.
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ABSTRACT:
SUBMITTER: Angrand PO
PROVIDER: S-EPMC4413816 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Project description:BackgroundGreen tea has been shown to improve cholesterol metabolism in animal studies, but the molecular mechanisms underlying this function have not been fully understood. Long non-coding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases. Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate (EGCG) on cholesterol metabolism.MethodsMicroarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol(-)-epigallocatechin gallate in cultured human liver (HepG2) hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships. RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism.ResultsThe expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment. Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA. In particular, the lncRNA AT102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) were identified. Using a real-time polymerase chain reaction technique, we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression of AT102202. After AT102202 knockdown in HepG2, we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control (P < 0.05).ConclusionsOur results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells. LncRNAs may play an important role in the cholesterol metabolism.
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Project description:Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Despite the advances in the knowledge of pathogenetic molecular mechanisms and the implementation of more effective drug treatments in recent years, the overall survival rate of patients remains unsatisfactory. The high death rate is mainly due to metastasis of cancer in about half of the cancer patients and the emergence of drug-resistant populations of cancer cells. Improved understanding of cancer molecular biology has highlighted the role of non-coding RNAs (ncRNAs) in colorectal cancer development and evolution. ncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions of long non-coding RNAs (lncRNAs) with both microRNAs (miRNAs) and proteins, and through the action of lncRNAs as miRNA precursors or pseudogenes. LncRNAs can also be detected in the blood and circulating ncRNAs have become a new source of non-invasive cancer biomarkers for the diagnosis and prognosis of colorectal cancer, as well as for predicting the response to drug therapy. In this review, we focus on the role of lncRNAs in colorectal cancer development, progression, and chemoresistance, and as possible therapeutic targets.
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Project description:Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being "transcriptional noise", increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.
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Project description:The perception of long non-coding RNAs as chunk RNA and transcriptional noise has been steadily replaced by their role as validated targets for a diverse set of physiological processes in the past few years. However, for the vast majority of lncRNAs their precise mode of action and physiological function remain to be uncovered. A large body of evidence has revealed their essential role in all stages of cancirogenesis and metastasis. In this review we focus on the role of lncRNAs in metastasis. We grouped selected lncRNAs into three categories based on in vitro and in vivo mode of action-related studies and clinical relevance for metastasis. Grouped according to their mode of action, in category I we discuss lncRNAs such as CCAT2, DREH, LET, NKILA, treRNA, HOTAIR, H19, FENDRR, lincROR, MALAT, GClnc1, BCAR4, SCHLAP1 and lncRNA ATP, all lncRNAs with in vitro and in vivo metastasis-related data and clinical significance. In category II we discuss lncRNAs CCAT1, PCAT1, PTENgp1, GPLINC, MEG3, ZEB2-AS, LCT13, ANRIL, NBAT1 and lncTCF7 all characterized by their mode of action in vitro and clinical significance, but pending or preliminary in vivo data. Finally, under category III, we discuss lncRNAs BANCR, FRLnc1, SPRY4-IT1 and LIMT with partially or poorly-resolved mode of action and varying degree of validation in clinical metastasis. Finally we discuss metastasis-related translational aspects of lncRNAs.
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Project description:Ovarian cancer is the most fatal tumor of female's reproductive system, and several genetics and environmental factors are involved in its development. Various studies have already identified some suitable biomarkers to facilitate the early detection, the prognosis evaluation, and the assessment of treatment response. However, the aim of this review is to investigate the role of long non-coding RNAs (lncRNAs) in tumorigenesis process of ovarian cancer and their potential applications as ovarian cancer biomarkers. We performed an online literature search of the MEDLINE/PubMed databases using the keywords, including ovarian cancer, lncRNA, and biomarker. We found that several lncRNAs have been shown to be deregulated in ovarian cancer and the specific mechanism of their enrollment in ovarian cancer has been defined for a few of them. In addition, expression profiling has revealed an association between lncRNAs and patients' survival, metastasis potential, as well as treatment response. Expression profiling and methylation analysis of lncRNAs in ovarian cancer may lead to the identification of novel biomarkers that can help in the classification of patients based on prognosis and treatment response.
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Project description:Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.
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