Long noncoding RNAs (lncRNAs) do not code for proteins but function as RNAs. Because the functions of an RNA rely More »
COLUMBUS, Ohio – A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. More »
Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature
Despite the inarguable relevance of p53 in cancer, genome-wide studies relating endogenous p53 activity to the expression of lncRNAs in human cells are still missing. Here, by integrating RNA-seq with p53 ChIP-seq analyses of a human cancer cell line under DNA damage, researchers from the Universidad de Navarra, Spain define a high-confidence set of 18 lncRNAs that are p53 transcriptional targets. The researchers demonstrate that two of the p53-regulated lncRNAs are required for the efficient binding of p53 to some of its target genes, modulating the p53 transcriptional network and contributing to apoptosis induction by DNA damage. They also show that the expression of p53-lncRNAs is lowered in colorectal cancer samples, constituting a tumour suppressor signature with high diagnostic power. Thus, p53-regulated lncRNAs establish a positive regulatory feedback loop that enhances p53 tumour suppressor activity. Furthermore, the signature defined by p53-regulated lncRNAs supports their potential use in the clinic as biomarkers and therapeutic targets.
- Sánchez Y, Segura V, Marín-Béjar O, Athie A, Marchese FP, González J, Bujanda L, Guo S, Matheu A, Huarte M. (2014) Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature. Nat Commun 5:5812. [article]
An explanation of what lincRNA is, how it was discovered, and a special emphasis on TUNA, a recently discovered lincRNA.
Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes including cancer. To delineate genome-wide lncRNA expression, researchers at the University of Michigan curated 7,256 RNA sequencing (RNA-seq) libraries from tumors, normal tissues and cell lines comprising over 43 Tb of sequence from 25 independent studies. They applied ab initio assembly methodology to this data set, yielding a consensus human transcriptome of 91,013 expressed genes.
Over 68% (58,648) of genes were classified as lncRNAs, of which 79% were previously unannotated. About 1% (597) of the lncRNAs harbored ultraconserved elements, and 7% (3,900) overlapped disease-associated SNPs. To prioritize lineage-specific, disease-associated lncRNA expression, the reseaechers employed non-parametric differential expression testing and nominated 7,942 lineage- or cancer-associated lncRNA genes. The lncRNA landscape characterized here may shed light on normal biology and cancer pathogenesis and may be valuable for future biomarker development.
Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, Poliakov A, Cao X, Dhanasekaran SM, Wu YM, Robinson DR, Beer DG, Feng FY, Iyer HK, Chinnaiyan AM. (2015) The landscape of long noncoding RNAs in the human transcriptome. Nat Genet [Epub ahead of print]. [abstract]
A new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) describes a novel marker that might help doctors choose the least toxic, most effective treatment for many older patients with acute myeloid leukemia (AML). AML occurs mainly in older patients and has a three-year survival rate of 5 to 15 percent.
The researchers investigated patterns of molecules called long noncoding RNAs (lncRNAs), a class of RNA molecules more than 200 nucleotide units long that are involved in regulating genes. The researchers examined the abundance, or expression, of lncRNAs in patients who were 60 years and older and who had cytogenetically normal (CN) AML.
The study is published online in the Proceedings of the National Academy of Sciences.
A wiki-style database hopes to serve as an online encyclopedia of lncRNA by and for the scientific community.
Scientists have set up a long non-coding RNA (lncRNA) database aimed at harnessing the collective knowledge of the scientific community. This study has been published in Nucleic Acids Research.
LncRNAs are RNAs that do not code for proteins but are nonetheless actively transcribed in human genome. In recent years, it has been recognized that they perform significant roles in a large variety of biological processes. The dysregulation of lncRNA expression is highly correlated with human cancer, neurological disorders, and many other human diseases.