Search Results for: long noncoding rna expression

The functional characterization of long noncoding RNA SPRY4-IT1 in human melanoma cells

Expression of the long noncoding RNA (lncRNA) SPRY4-IT1 is low in normal human melanocytes but high in melanoma cells. siRNA knockdown of SPRY4-IT1 blocks melanoma cell invasion and proliferation, and increases apoptosis.

To investigate its function further, a team led by researchers at the Sanford-Burnham Medical Research Institute affinity purified SPRY4-IT1 from melanoma cells and used mass spectrometry to identify the protein lipin 2, an enzyme that converts phosphatidate to diacylglycerol (DAG), as a major binding partner. SPRY4-IT1 knockdown increases the accumulation of lipin2 protein and upregulate the expression of diacylglycerol O-acyltransferase 2 (DGAT2) an enzyme involved in the conversion of DAG to triacylglycerol (TAG). When SPRY4-IT1 knockdown and control melanoma cells were subjected to shotgun lipidomics, an MS-based assay that permits the quantification of changes in the cellular lipid profile, the team found that SPRY4-IT1 knockdown induced significant changes in a number of lipid species, including increased acyl carnitine, fatty acyl chains, and triacylglycerol (TAG). Together, these results suggest the possibility that SPRY4-IT1 knockdown may induce apoptosis via lipin 2-mediated alterations in lipid metabolism leading to cellular lipotoxicity.

lncRNA

  • Mazar J, Zhao W, Khalil AM, Lee B, Shelley J, Govindarajan SS, Yamamoto F, Ratnam M, Aftab MN, Collins S, Finck BN, Han X, Mattick JS, Dinger ME, Perera RJ. (2014) The functional characterization of long noncoding RNA SPRY4-IT1in human melanoma cells. Oncotarget [Epub ahead of print]. [article]

Incoming search terms:

  • LNCRNA function in melanoma

Tissue-Specific RNA-Seq in Human Evoked Inflammation Identifies Blood and Adipose LincRNA Signatures

Inappropriate transcriptional activation of innate immunity is a pathological feature of several cardiometabolic disorders, but little is known about inflammatory modulation of long intergenic noncoding RNAs (lincRNAs) in disease-relevant human tissues.

Researchers at the University of Pennsylvania applied deep RNA sequencing (>500 million filtered reads per sample) to blood and adipose during low-dose experimental endotoxemia (lipopolysaccharide) in a healthy human, with targeted replication in separate individuals undergoing endotoxemia (n=6), to identify inflammatory lincRNAs. A subset of these lincRNAs was examined for expression in adipocytes and monocytes, modulation in adipose of obese humans, and overlap with genome-wide association study signals for inflammatory and cardiometabolic traits. Of a stringent set of 4284 lincRNAs, ≈11% to 22% were expressed with 201 and 56 lincRNAs modulated by lipopolysaccharide in blood or adipose, respectively. Tissue-specific expression of a subset of 6 lipopolysaccharide-lincRNAs was replicated with lipopolysaccharide modulation confirmed for all 3 expressed in blood and 2 of 4 expressed in adipose. The broader generalizability of findings in blood of subject A was confirmed by RNA sequencing in 7 additional subjects. The researchers confirmed adipocytes and monocytes as potential cell-sources of selective lipopolysaccharide-regulated lincRNAs, and 2 of these, linc-DMRT2 (P=0.002) and linc-TP53I13 (P=0.01), were suppressed in adipose of obese humans. Finally, they provide examples of lipopolysaccharide-modulated lincRNAs that overlap single nucleotide polymorphisms that are associated with cardiometabolic traits.

lncRNA

These findings provide novel insights into tissue-level, inflammatory transcriptome regulation in cardiometabolic diseases. These are complementary to more usual approaches limited to interrogation of DNA variations.

  • Liu Y1, Ferguson JF, Xue C, Ballantyne RL, Silverman IM, Gosai SJ, Serfecz J, Morley MP, Gregory BD, Li M, Reilly MP. (2014) Tissue-Specific RNA-Seq in Human Evoked Inflammation Identifies Blood and Adipose LincRNA Signatures of Cardiometabolic Diseases. Arterioscler Thromb Vasc Biol 34(4), 902-12. [abstract]

Incoming search terms:

  • define incrnas
  • incRNA physiology
  • incrna terminology
  • linc rna library
  • lincrna news
  • what are incrnas

The four dimensions of noncoding RNA conservation

Evolutionary conservation is widely used as an indicator of the functional significance of newly discovered genes. Although the simple search for homology at the nucleotide or amino acid sequence level has proven to be valuable for protein-coding genes, these criteria are too narrow to describe fully the selection process for long noncoding RNAs (lncRNAs). LncRNA conservation includes four dimensions: the sequence, structure, function, and expression from syntenic loci. Two recently described knockout mouse models for the lincRNAs metastasis associated lung adenocarcinoma transcript 1 (Malat1) and HOX antisense intergenic RNA (Hotair) highlight the multifaceted levels of conservation.

lncRNA

  • Diederichs S. (2014) The four dimensions of noncoding RNA conservation. Trends Genet  [Epub ahead of print]. [abstract]

Incoming search terms:

  • hot air cold air RNA GENETIC
  • lincRNA-P21 down regulated
  • msur1lncRNA
  • NONCODE 4 0
  • The Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth

Featured long non-coding RNA – PCAT-1

lncRNA

Impairment of double-stranded DNA break (DSB) repair is essential to many cancers. However, although mutations in DSB repair proteins are common in hereditary cancers, mechanisms of impaired DSB repair in sporadic cancers remain incompletely understood.

Here, a team led by researchers at the Michigan Center for Translational Pathology describes the first role for a long noncoding RNA (lncRNA) in DSB repair in prostate cancer. They identify PCAT-1, a prostate cancer outlier lncRNA, which regulates cell response to genotoxic stress. PCAT-1 expression produces a functional deficiency in homologous recombination through its repression of the BRCA2 tumor suppressor, which, in turn, imparts a high sensitivity to small-molecule inhibitors of PARP1. These effects reflected a posttranscriptional repression of the BRCA2 3′UTR by PCAT-1. These observations thus offer a novel mechanism of “BRCAness” in sporadic cancers.

  • Prensner JR et al. (2014) PCAT-1, a Long Noncoding RNA, Regulates BRCA2 and Controls Homologous Recombination in Cancer. Cancer Res [Epub ahead of print]. [abstract]

Featured long non-coding RNA: CARLo-5

lncRNA

The mechanism by which the 8q24 MYC enhancer region, including cancer-associated variant rs6983267, increases cancer risk is unknown due to the lack of protein-coding genes at 8q24.21. Here a team led by researchers at the YanBian University, China report the identification of long noncoding RNAs named cancer-associated region long noncoding RNAs (CARLos) in the 8q24 region. The expression of one of the long noncoding RNAs, CARLo-5, is significantly correlated with the rs6983267 allele associated with increased cancer susceptibility. They also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. Finally, the researchers demonstrate that CARLo-5 has a function in cell-cycle regulation and tumor development. Overall, these data provide a key of the mystery of the 8q24 gene desert.

  • Kim T, Cui R, Jeon YJ, Lee JH, Lee JH, Sim H, Park JK, Fadda P, Tili E, Nakanishi H, Huh MI, Kim SH, Cho JH, Sung BH, Peng Y, Lee TJ, Luo Z, Sun HL, Wei H, Alder H, Oh JS, Shim KS, Ko SB, Croce CM. (2014) Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proc Natl Acad Sci U S A [Epub ahead of print]. [abstract]

Incoming search terms:

  • 8q24 lncrna
  • Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5