Long non-coding RNAs (lncRNAs) are emerging as important regulatory molecules in developmental, physiological, and pathological processes. However, the precise mechanism More »
Action of a key lncRNA different in colon cancer versus normal colon tissue Genetics researchers from Case Western Reserve School More »
MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures
Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. Researchers More »
LNCipedia collects long non-coding RNA sequences and annotation from different sources. In version 3.0, over 90,000 new transcripts were added More »
Pancreatic ductal adenocarcinoma (PDAC), a common digestive system cancer, is highly malignant and has a poor disease outcome. Currently, all available examination and detection methods cannot accurately predict the clinical outcome. Therefore, it is extremely important to identify novel molecular biomarkers for personalized medication and to significantly improve the overall outcome. The “noncoding RNAs” (ncRNAs) are a group of RNAs that do not code for proteins, and they are categorized as structural RNAs and regulatory RNAs. It has been shown that microRNAs and long ncRNAs function as regulatory RNAs to affect the progression of various diseases. Many studies have confirmed a role for ncRNAs in the progression of PDAC during the last few years. Because of the significant role of ncRNAs in PDAC, ncRNA profiling may be used to predict PDAC outcome with high accuracy. This review comprehensively analyzes the value of ncRNAs as potential biomarkers to predict the outcome in PDAC and the possible mechanisms thereof.
- Jin K, Luo G, Xiao Z, Liu Z, Liu C, Ji S, Xu J, Liu L, Long J, Ni Q, Yu X. (2015) Noncoding RNAs as potential biomarkers to predict the outcome in pancreatic cancer. Drug Des Devel Ther 9:1247-1255. [article]
The central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs (lncRNAs) have attracted much attention due to their large number and biological significance. Many lncRNAs have been identified as mapping to regulatory elements including gene promoters and enhancers, ultraconserved regions and intergenic regions of protein-coding genes. Yet, the biological function and molecular mechanisms of lncRNA in human diseases in general and cancer in particular remain largely unknown. Data from the literature suggest that lncRNA, often via interaction with proteins, functions in specific genomic loci or use their own transcription loci for regulatory activity.
In this review, the authors summarize recent findings supporting the importance of DNA loci in lncRNA function and the underlying molecular mechanisms via cis or trans regulation, and discuss their implications in cancer. In addition, they use the 8q24 genomic locus, a region containing interactive SNPs, DNA regulatory elements and lncRNAs, as an example to illustrate how single-nucleotide polymorphism (SNP) located within lncRNAs may be functionally associated with the individual’s susceptibility to cancer.
- Ling H, Vincent K, Pichler M, Fodde R, Berindan-Neagoe I, Slack FJ, Calin GA. (2015) Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene [Epub ahead of print].[abstract]
In recent years, increasing evidence suggests that noncoding RNAs play important roles in the regulation of tissue homeostasis and pathophysiological conditions. Besides small noncoding RNAs (eg, microRNAs), >200-nucleotide long transcripts, namely long noncoding RNAs (lncRNAs), can interfere with gene expressions and signaling pathways at various stages. In the cardiovascular system, studies have detected and characterized the expression of lncRNAs under normal physiological condition and in disease states. Several lncRNAs are regulated during acute myocardial infarction (eg, Novlnc6) and heart failure (eg, Mhrt), whereas others control hypertrophy, mitochondrial function and apoptosis of cardiomyocytes. In the vascular system, the endothelial-expressed lncRNAs (eg, MALAT1 and Tie-1-AS) can regulate vessel growth and function, whereas the smooth-muscle-expressed lncRNA smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA was recently shown to control the contractile phenotype of smooth muscle cells.
This review article summarizes the data on lncRNA expressions in mouse and human and highlights identified cardiovascular lncRNAs that might play a role in cardiovascular diseases. Although our understanding of lncRNAs is still in its infancy, these examples may provide helpful insights how lncRNAs interfere with cardiovascular diseases.
- Uchida S, Dimmeler S. (2015) Long Noncoding RNAs in Cardiovascular Diseases. Circ Res 116(4):737-750. [article]
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It is a great surprise that the genomes of mammals and other eukaryotes harbor many thousands of long noncoding RNAs (lncRNAs). Although these long noncoding transcripts were once considered to be simply transcriptional noise or cloning artifacts, multiple studies have suggested that lncRNAs are emerging as new players in diverse human diseases, especially in cancer, and that the molecular mechanisms of lncRNAs need to be elucidated.
More recently, evidence has begun to accumulate describing the complex post-transcriptional regulation in which lncRNAs are involved. It was reported that lncRNAs can be implicated in degradation, translation, pre-messenger RNA (mRNA) splicing, and protein activities and even as microRNAs (miRNAs) sponges in both a sequence-dependent and sequence-independent manner. In this review, the authors present an updated vision of lncRNAs and summarize the mechanism of post-transcriptional regulation by lncRNAs, providing new insight into the functional cellular roles that they may play in human diseases, with a particular focus on cancers.
- Shi X, Sun M, Wu Y, Yao Y, Liu H, Wu G, Yuan D, Song Y. (2015) Post-transcriptional regulation of long noncoding RNAs in cancer. Tumour Biol [Epub ahead of print]. [abstract]
Recent advances in RNA-sequencing technologies have led to the discovery of thousands of previously unannotated noncoding transcripts, including many long noncoding RNAs (lncRNAs) whose functions remain largely unknown. Discussed here are considerations and best practices in lncRNA identification and annotation, which we hope will foster functional and mechanistic exploration.
Perhaps the biggest surprise of the postgenomic era has been the enormous number and diversity of transcriptional products arising from the previously presumed wastelands of the non-protein-coding genome. These include a plethora of small regulatory RNAs and tens of thousands of polyadenylated and nonpolyadenylated lncRNAs that are antisense, intronic, intergenic and overlapping with respect to protein-coding loci. The functions of these transcripts are largely unknown, although there is increasing in vitro and in vivo evidence that lncRNAs have key roles across diverse biological processes, with an emerging theme of interfacing with epigenetic regulatory pathways. Thus, the sheer number and the increasing pace of discovery of new lncRNAs are accompanied by the growing challenge of their definition and annotation.
The broad term lncRNA refers to a transcript >200 nt in length that does not appear to contain a protein-coding sequence. The size threshold is an arbitrary but convenient biophysical cutoff that excludes most known, although still poorly understood, classes of small infrastructural and regulatory RNAs, such as tRNAs, small nuclear RNAs, small nucleolar RNAs and their derivatives, microRNAs, short interfering RNAs, Piwi-interacting RNAs, transcription-initiation RNAs and small RNAs that regulate splicing. Occasionally other terminology, such as transcripts of unknown function (TUFs) and transcriptionally active regions (TARs), has been suggested, but the consensus has settled on the generic descriptor lncRNA, at least for the time being. (read more…)
- Mattick JS, Rinn JL. (2015) Discovery and annotation of long noncoding RNAs. Nat Struct Mol Biol 22(1):5-7. [abstract]