Search Results for: long noncoding rna expression

MYC Regulated by Super-Enhancer Long Noncoding RNA in Colorectal Cancer

In the cover story published on May 5th, 2014 in Cell Research, the team led by CHEN Lingling from the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, presents a Colorectal Cancer (CRC) specific long noncoding RNA, CCAT1-L, in the regulation of MYC expression across over 500 kb in distance by participating in higher chromatin organization.

The expression of the human MYC oncogene is complex and regulated at multiple levels. One of the most mysterious regulations of MYC is that the megabase-sized region of human 8q24 gene desert around MYC contains many regulatory elements including enhancers and super-enhancers. These regulatory elements form looping interactions with MYC in a tissue-/tumor type-specific manner. However, how these chromatin loops in the MYC locus are regulated remains unknown.

Under supervision of Prof. CHEN Lingling, XIANG Jianfeng et al have identified a CRC specific long noncoding RNA, CCAT1-L, transcribed from 515k upstream of the MYC gene, a CRC specific super enhancer region. CCAT1-L accumulates to its sites of transcription, interacts with CTCF to facilitate the long-range chromatin interaction between distal enhancers and the MYC promoter. Knockdown of CCAT1-L decreases MYC expression by weakening the long-range interactions between the MYC promoter and its distal enhancers. In-cis activation of CCAT1-L with the TALEN technique minics endogenous CCAT1-L sub-cellular localization and function, upregulate MYC expression and promote tumorigenesis. This study leads to a better understanding of MYC regulation network and roles of lncRNAs in chromatin regulation.

lncrna

This study entitled Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus was published on Cell Research as a cover storyand highlighted by S.T. Younger and Rinn with a title of “‘Lnc’ -ing enhancers to MYC regulation” on April 29th, 2014, Cell Research. This work was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, and Chinese Academy of Sciences. 

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  • epigenetics superenhancer
  • call superenhancer code
  • chromatin looping at myc
  • mirna super-enhancers
  • myc and lncrna
  • myc lincrna
  • superenhancer

Featured lncRNA – ncRuPAR

lncRNA

ncRuPAR is a newly discovered long noncoding RNA molecule that can upregulate protease-activated receptor-1 (PAR-1) during embryonic growth; however, its role in cancer has not been elucidated. Here, researchers at the Second Military Medical University, China conducted a study to investigate the role of ncRuPAR in gastric cancer. Significant downregulation of ncRuPAR was detected in gastric cancer tissues compared with paired adjacent nontumor tissues; however, both PAR-1 and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) levels were significantly higher in cancerous tissues compared with adjacent normal tissues. Additionally, the expression level of ncRuPAR was found to be significantly correlated with tumor invasion depth, lymph node metastasis, distant metastasis, tumor size, and tumor-nodes-metastasis (TNM) stage and inversely associated with the mRNA levels and extent (E) × intensity (I) scores of PAR-1 and VEGF. The protein level of PAR-1 was significantly correlated with tumor size only, while the VEGF protein level was significantly correlated with invasion depth and tumor size. The area under the receiver operating characteristic (ROC) curve of ncRuPAR was 0.84 (95 % CI 0.79-0.88) at a cutoff value of 4.97; ncRuPAR had a sensitivity of 88.41 %, a specificity of 73.91 %, and an accuracy of 81.16 % for the prediction of gastric cancer. These results suggest that ncRuPAR inhibits gastric cancer development, and its underlying mechanism involves the inhibition of PAR-1. In addition, ncRuPAR could be regarded as a marker for gastric cancer in the future.

  • Liu L, Yan B, Yang Z, Zhang X, Gu Q, Yue X. (2014) ncRuPAR inhibits gastric cancer progression by down-regulating protease-activated receptor-1. Tumour Biol [Epub ahead of print]. [abstract]

Incoming search terms:

  • gastric cancer blogs
  • LNCRNA predicted target search
  • ncRNA target gene prediction
  • programs to predict targets of long non-coding rnas

lncRNAtor – Functional Investigation of long noncoding RNAs

lncRNAtor aims to be the lncRNA (long non-coding RNA) portal encompassing expression profile, interacting (binding) protein, integrated sequence curation, evolutionary scores, and coding potential. Data sets were collected from TCGA, GEO, ENCODE, and modENCODE (Organism: Human, Mouse, Fly, Worm, and Yeast). Our system workflow is shown below.

lncRNA

  • lncRNAtor is preparing to submit a paper. (2013.06.03)

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  • lncrnator

Species-specific alternative splicing leads to unique expression of sno-lncRNAs

Intron-derived long noncoding RNAs with snoRNA ends (sno-lncRNAs) are highly expressed from the imprinted Prader-Willi syndrome (PWS) region on human chromosome 15. However, sno-lncRNAs from other regions of the human genome or from other genomes have not yet been documented.

By exploring non-polyadenylated transcriptomes from human, rhesus and mouse, researchers at the Shanghai Institutes for Biological Sciences have systematically annotated sno-lncRNAs expressed in all three species. In total, using available data from a limited set of cell lines, 19 sno-lncRNAs have been identified with tissue- and species-specific expression patterns. Although primary sequence analysis revealed that snoRNAs themselves are conserved from human to mouse, sno-lncRNAs are not. PWS region sno-lncRNAs are highly expressed in human and rhesus monkey, but are undetectable in mouse. Importantly, the absence of PWS region sno-lncRNAs in mouse suggested a possible reason why current mouse models fail to fully recapitulate pathological features of human PWS. In addition, a RPL13A region sno-lncRNA was specifically revealed in mouse embryonic stem cells, and its snoRNA ends were reported to influence lipid metabolism. Interestingly, the RPL13A region sno-lncRNA is barely detectable in human. The researchers further demonstrated that the formation of sno-lncRNAs is often associated with alternative splicing of exons within their parent genes, and species-specific alternative splicing leads to unique expression pattern of sno-lncRNAs in different animals.

lncRNA

Comparative transcriptomes of non-polyadenylated RNAs among human, rhesus and mouse revealed that the expression of sno-lncRNAs is species-specific and that their processing is closely linked to alternative splicing of their parent genes. This study thus further demonstrates a complex regulatory network of coding and noncoding parts of the mammalian genome.

  • Zhang XO, Yin QF, Wang HB, Zhang Y, Chen T, Zheng P, Lu X, Chen LL, Yang L. (2014) Species-specific alternative splicing leads to unique expression of sno-lncRNAs. BMC Genomics 15(1), 287. [abstract]

Incoming search terms:

  • long
  • Intimate Relationship Among a MicroRNA Long Noncoding RNA and mRNA
  • lincrna metabolism
  • lncrna are they spliced
  • long noncoding rna profiles identify five distinct molecular subtypes of col
  • stem cell rna-seq

Species-specific alternative splicing leads to unique expression of sno-lncRNAs

Intron-derived long noncoding RNAs with snoRNA ends (sno-lncRNAs) are highly expressed from the imprinted Prader-Willi syndrome (PWS) region on human chromosome 15. However, sno-lncRNAs from other regions of the human genome or from other genomes have not yet been documented.

By exploring non-polyadenylated transcriptomes from human, rhesus and mouse, we have systematically annotated sno-lncRNAs expressed in all three species. In total, using available data from a limited set of cell lines, 19 sno-lncRNAs have been identified with tissue- and species-specific expression patterns. Although primary sequence analysis revealed that snoRNAs themselves are conserved from human to mouse, sno-lncRNAs are not. PWS region sno-lncRNAs are highly expressed in human and rhesus monkey, but are undetectable in mouse. Importantly, the absence of PWS region sno-lncRNAs in mouse suggested a possible reason why current mouse models fail to fully recapitulate pathological features of human PWS. In addition, a RPL13A region sno-lncRNA was specifically revealed in mouse embryonic stem cells, and its snoRNA ends were reported to influence lipid metabolism. Interestingly, the RPL13A region sno-lncRNA is barely detectable in human. Researchers at the Shanghai Institutes for Biological Sciences further demonstrated that the formation of sno-lncRNAs is often associated with alternative splicing of exons within their parent genes, and species-specific alternative splicing leads to unique expression pattern of sno-lncRNAs in different animals.

lncRNA

Comparative transcriptomes of non-polyadenylated RNAs among human, rhesus and mouse revealed that the expression of sno-lncRNAs is species-specific and that their processing is closely linked to alternative splicing of their parent genes. This study thus further demonstrates a complex regulatory network of coding and noncoding parts of the mammalian genome.

  • Zhang XO, Yin QF, Wang HB, Zhang Y, Chen T, Zheng P, Lu X, Chen LL, Yang L. (2014) Species-specific alternative splicing leads to unique expression of sno-lncRNAs. BMC Genomics 15(1), 287. [abstract]