In this review I focus on the role of splicing in long non-coding RNA (lncRNA) life. First, I summarize differences between the splicing efficiency of protein-coding genes and lncRNAs and discuss why non-coding RNAs are spliced less efficiently. In the second half of the review, I speculate why splice sites are the most conserved sequences in lncRNAs and what additional roles could splicing play in lncRNA metabolism. I discuss the hypothesis that the splicing machinery can, besides its dominant role in intron removal and exon joining, protect cells from undesired transcripts.
- Keywords
- SR proteins, large intervening non-coding RNA, snRNP, spliceosomes, splicing,
- MeSH
- RNA, Long Noncoding * genetics MeSH
- RNA Splicing MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- RNA, Long Noncoding * MeSH
Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.
- Keywords
- biomarker, epigenetic factors, non-coding RNA, osteoarthritis, targeted treatment,
- MeSH
- RNA, Circular MeSH
- Humans MeSH
- MicroRNAs * genetics MeSH
- Osteoarthritis * genetics MeSH
- Piwi-Interacting RNA MeSH
- RNA, Long Noncoding * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- RNA, Circular MeSH
- MicroRNAs * MeSH
- Piwi-Interacting RNA MeSH
- RNA, Long Noncoding * MeSH
Cardiac arrhythmias represent wide and heterogenic group of disturbances in the cardiac rhythm. Pathophysiology of individual arrhythmias is highly complex and dysfunction in ion channels/currents involved in generation or spreading of action potential is usually documented. Non-coding RNAs (ncRNAs) represent highly variable group of molecules regulating the heart expression program, including regulation of the expression of individual ion channels and intercellular connection proteins, e.g. connexins.Within this chapter, we will describe basic electrophysiological properties of the myocardium. We will focus on action potential generation and spreading in pacemaker and non-pacemaker cells, including description of individual ion channels (natrium, potassium and calcium) and their ncRNA-mediated regulation. Most of the studies have so far focused on microRNAs, thus, their regulatory function will be described into greater detail. Clinical consequences of altered ncRNA regulatory function will also be described together with potential future directions of the research in the field.
- Keywords
- Arrhythmia, CACNA1C, Connexin 43, Ion channels, MicroRNA, Non-coding RNA,
- MeSH
- Ion Channels MeSH
- Humans MeSH
- MicroRNAs MeSH
- RNA, Untranslated * MeSH
- Heart MeSH
- Arrhythmias, Cardiac * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Ion Channels MeSH
- MicroRNAs MeSH
- RNA, Untranslated * MeSH
The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.
- Keywords
- cancer, delivery systems, long non-coding RNA, microRNA, non-coding RNA, therapy,
- MeSH
- Molecular Targeted Therapy methods trends MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Models, Genetic MeSH
- Neoplasms drug therapy genetics MeSH
- RNA, Untranslated genetics MeSH
- Antineoplastic Agents therapeutic use MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- RNA, Long Noncoding genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- MicroRNAs MeSH
- RNA, Untranslated MeSH
- Antineoplastic Agents MeSH
- RNA, Long Noncoding MeSH
Whole-genome sequencing analyses revealed that the majority of the human genome is transcribed and identified thousands of protein non-coding transcripts. Non-coding RNAs (ncRNAs) are divided into two main groups: small and long ncRNAs. This review is focused on the regulatory ncRNAs mainly on microRNAs and long ncRNAs. These ncRNAs regulate gene expression at the transcriptional and post-transcriptional levels. In this context, ncRNAs are involved in the regulation of most cellular processes and their deregulation has serious impacts on the phenotype. Hundreds of studies have implicated ncRNAs in the pathogenesis of many diseases ranging from metabolic disorders to diseases of organ systems as well as various types of cancers.Clinically, ncRNAs belong to a new generation of diagnostic and prognostic biomarkers with a great potential. Due to high tissue specificity and ability to regulate multiple genes often within one signaling pathway, ncRNAs represent attractive therapeutic targets. Increasing knowledge about a wide spectrum of ncRNA actions demonstrate a pivotal role of these transcripts in expression regulation. Many aspects of the ncRNA biology are still unclear and their understanding will provide us a new perspective on the complexity of the regulatory network.
- Keywords
- gene expression regulation, miRNA lncRNA., non-coding RNA,
- MeSH
- Humans MeSH
- MicroRNAs genetics physiology MeSH
- RNA, Untranslated genetics physiology MeSH
- Gene Expression Regulation genetics physiology MeSH
- RNA, Long Noncoding genetics physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- MicroRNAs MeSH
- RNA, Untranslated MeSH
- RNA, Long Noncoding MeSH
A colorectal adenoma, an aberrantly growing tissue, arises from the intestinal epithelium and is considered as precursor of colorectal cancer (CRC). In this study, we investigated structural and numerical chromosomal aberrations in adenomas, hypothesizing that chromosomal instability (CIN) occurs early in adenomas. We applied array comparative genomic hybridization (aCGH) to fresh frozen colorectal adenomas and their adjacent mucosa from 16 patients who underwent colonoscopy examination. In our study, histologically similar colorectal adenomas showed wide variability in chromosomal instability. Based on the obtained results, we further stratified patients into four distinct groups. The first group showed the gain of MALAT1 and TALAM1, long non-coding RNAs (lncRNAs). The second group involved patients with numerous microdeletions. The third group consisted of patients with a disrupted karyotype. The fourth group of patients did not show any CIN in adenomas. Overall, we identified frequent losses in genes, such as TSC2, COL1A1, NOTCH1, MIR4673, and GNAS, and gene gain containing MALAT1 and TALAM1. Since long non-coding RNA MALAT1 is associated with cancer cell metastasis and migration, its gene amplification represents an important event for adenoma development.
- Keywords
- MALAT1, adenomas, array comparative genomic hybridization, colorectal cancer, long non-coding RNA,
- MeSH
- Adenoma * genetics pathology MeSH
- Chromosomal Instability MeSH
- Colorectal Neoplasms * genetics pathology MeSH
- Humans MeSH
- Precancerous Conditions * genetics pathology MeSH
- RNA, Long Noncoding * genetics MeSH
- Comparative Genomic Hybridization MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- MALAT1 long non-coding RNA, human MeSH Browser
- RNA, Long Noncoding * MeSH
BACKGROUND: Lung cancer is one of the most fatal human cancers both in males and females. This type of cancer is categorized to different subtypes among them is non-small cell lung cancer (NSCLC). NSCLC accounts for about 80% of all cases. Long non-coding RNAs (lncRNAs) have been shown to influence the pathogenic course of lung cancer. However, the contribution of LINC01433 lncRNA in this type of cancer in Iranian patients is not clear. PURPOSE: In the current project, we evaluated expression of LINC01433 in 42 NSCLC samples and their paired non-tumoral tissues using quantitative real time polymerase chain reaction method. Samples were collected from patients admitted to Labbafinejad Hospital during 2016-2017. RESULTS: There was no significant difference in the expression of LINC01433 between tumoral and non-tumoral tissues (expression ratio 0.67, p = 0.42). Expression of this lncRNA was not associated with any of clinical and demographic data including age, gender, smoking history, stage or cancer subtype. CONCLUSION: Based on the similar expression levels of this lncRNA between tumoral and non-tumoral tissues and lack of association between expression levels and clinical data, this lncRNA is not a possible contributor to lung cancer in Iranian patients. However, expression analysis of this lncRNA in larger sample sizes is needed to verify our results.
- Keywords
- expression, long non-coding RNA, lung cancer,
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Lung Neoplasms genetics pathology MeSH
- Carcinoma, Non-Small-Cell Lung genetics pathology MeSH
- Lung metabolism MeSH
- RNA, Long Noncoding * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Iran MeSH
- Names of Substances
- RNA, Long Noncoding * MeSH
The molecular target of mycotoxins is not fully understood. Extensive data derived from cell and animal experimental studies demonstrate that long non-coding RNAs (lncRNAs) play crucial roles in mycotoxin-induced toxicities. Mycotoxins stimulate the upregulation/downregulation of lncRNA expression, which further promote apoptosis, is related to the mTOR/FoxO signaling pathway, and contributes to tumor cell growth, death, and liver and chondrocyte damage. Moreover, lncRNA can establish interactions with NF-κB and cause immune evasion. These preliminary data suggest that lncRNAs are involved in potential upstream regulatory events and further regulate downstream apoptosis, oxidative stress, and anti-apoptotic events that affect cell death and survival. Therefore, we hypothesize that lncRNAs are potential targets of mycotoxins. Investigation of the expression of the potential target lncRNAs by mycotoxin-mediated stimulation, and exploration of the upstream and downstream relationship between lncRNA and the key proteins involved in mycotoxin toxicity, should be performed. This Hypothesis provides clues for further understanding of the molecular mechanisms of mycotoxins.
- Keywords
- Long non-coding RNA, Mycotoxins, Oxidative stress, Target, Toxicity mechanism,
- MeSH
- Apoptosis drug effects MeSH
- Autophagy drug effects MeSH
- Humans MeSH
- Mycotoxins pharmacology MeSH
- Cell Line, Tumor MeSH
- Oxidative Stress drug effects MeSH
- RNA, Long Noncoding metabolism MeSH
- Tumor Escape drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Mycotoxins MeSH
- RNA, Long Noncoding MeSH
Cytoplasmic male sterility (CMS) is a widespread phenomenon in flowering plants caused by mitochondrial (mt) genes. CMS genes typically encode novel proteins that interfere with mt functions and can be silenced by nuclear fertility-restorer genes. Although the molecular basis of CMS is well established in a number of crop systems, our understanding of it in natural populations is far more limited. To identify CMS genes in a gynodioecious plant, Silene vulgaris, we constructed mt transcriptomes and compared transcript levels and RNA editing patterns in floral bud tissue from female and hermaphrodite full siblings. The transcriptomes from female and hermaphrodite individuals were very similar overall with respect to variation in levels of transcript abundance across the genome, the extent of RNA editing, and the order in which RNA editing and intron splicing events occurred. We found only a single genomic region that was highly overexpressed and differentially edited in females relative to hermaphrodites. This region is not located near any other transcribed elements and lacks an open-reading frame (ORF) of even moderate size. To our knowledge, this transcript would represent the first non-coding mt RNA associated with CMS in plants and is, therefore, an important target for future functional validation studies.
- Keywords
- Cytoplasmic male sterility, Silene vulgaris, editing, mitochondrion, non-coding RNA, splicing, transcriptome.,
- MeSH
- RNA Editing MeSH
- Flowers genetics growth & development MeSH
- Genes, Mitochondrial * MeSH
- RNA, Untranslated * MeSH
- Plant Infertility * MeSH
- Plant Proteins genetics metabolism MeSH
- Silene genetics physiology MeSH
- Transcriptome * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Names of Substances
- RNA, Untranslated * MeSH
- Plant Proteins MeSH
BACKGROUND: To provide an overview of the importance of long non-coding RNAs (lncRNAs) in the pathogenesis of renal cell carcinoma and their utility as bio-markers for dia-gnosis, prognosis and prediction of treatment response. MATERIALS AND METHODS: A literature search in the Pubmed and Web of Science databases using the keywords variations of “long non-coding RNA” (“lncRNA”, “long noncoding RNA”, “long non-coding RNA”) and “renal cell carcinoma” (“renal cancer”, “renal cell carcinoma”, “kidney cancer”) was performed. The results related to the pathogenesis, dia-gnosis, prognosis and use as therapeutic targets were separated. RESULTS: Long non-coding RNAs regulate gene expression at different levels. They act both as oncogenes and tumor suppressors. The mechanism of their action has not been fully elucidated, but they are actively involved in the regulation of hypoxia inducible factors pathway, epithelial-mesenchymal transition, cell proliferation, cell cycle regulation, apoptosis, local invasion and development of metastases. Aberrant expression in tumor tissue compared to healthy parenchyma and the correlation of expression levels with clinical-pathological features allow the potential use of many lncRNAs as bio-markers for early detection and prognosis of the disease, including the response to targeted therapy. In vitro assays indicate the potential use of lncRNAs as therapeutic targets. CONCLUSION: Our knowledge of long non-coding RNAs in relation to renal cell carcinoma is increasing rapidly. At present, some of them can be considered as promising bio-markers. Further research is needed before they can be introduced into routine clinical practice.
- Keywords
- biomarker, diagnosis, long non-coding RNA, prognosis, renal cell carcinoma,
- MeSH
- Cell Cycle genetics MeSH
- Epithelial-Mesenchymal Transition genetics MeSH
- Carcinoma, Renal Cell diagnosis genetics mortality therapy MeSH
- Humans MeSH
- Biomarkers, Tumor genetics MeSH
- Kidney Neoplasms diagnosis genetics mortality therapy MeSH
- Prognosis MeSH
- Cell Proliferation genetics MeSH
- Gene Expression Regulation, Neoplastic MeSH
- RNA, Long Noncoding genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Biomarkers, Tumor MeSH
- RNA, Long Noncoding MeSH
