Long non-coding RNA expression profiles predict clinical phenotypes in glioma

Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
Neurobiology of Disease (Impact Factor: 5.08). 06/2012; 48(1):1-8. DOI: 10.1016/j.nbd.2012.06.004
Source: PubMed

ABSTRACT Glioma is the commonest form of primary brain tumor in adults with varying malignancy grades and histological subtypes. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been shown to play important roles in cancer development. To discover novel tumor-related lncRNAs and determine their associations with glioma subtypes, we first applied a lncRNA classification pipeline to identify 1970 lncRNAs that were represented on Affymetrix HG-U133 Plus 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published glioma gene expression profiles of 268 clinical specimens, and identified sets of lncRNAs that were unique to different histological subtypes (astrocytic versus oligodendroglial tumors) and malignancy grades. These lncRNAs signatures were then subject to validation in another non-overlapping, independent data set that contained 157 glioma samples. This is the first reported study that correlates lncRNA expression profiles with malignancy grade and histological differentiation in human gliomas. Our findings indicate the potential roles of lncRNAs in the biogenesis, development and differentiation of gliomas, and provide an important platform for future studies.

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    • "First of all, the probable mechanism of action of lncRNAs has not been delineated due to its heterogeneity [42]. Secondly, although Affymetrix HG-U133 Plus 2.0 array series is one of the most commonly used commercial microarrays in human cancer profiling, it does not represent all of the possible lncRNAs presented [18]. Thirdly, the sample size of each dataset is relatively small, which may reduce the accuracy of the results. "
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    Lung Cancer 08/2014; 85(2). DOI:10.1016/j.lungcan.2014.05.011 · 3.96 Impact Factor
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    • "CRNDE was originally discovered as an upregulated gene in colorectal adenomas and cancers, whereas it shows little to no expression in normal colon epithelium [1]. In addition to CRC, CRNDE overexpression has been observed in many other cancers, including gliomas in which it is the most upregulated lncRNA [2] [3]. CRNDE is a long non-coding RNA (lncRNA), defined as a class of non-protein coding transcripts over 200 nucleotides long; there is now abundant evidence for lncRNA roles in critical cellular processes, especially transcriptional and epigenetic regulation . "
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    ABSTRACT: Colorectal neoplasia differentially expressed (CRNDE) is a novel gene that is activated early in colorectal cancer but whose regulation and functions are unknown. CRNDE transcripts are recognized as long noncoding RNAs (lncRNAs), which potentially interact with chromatin-modifying complexes to regulate gene expression via epigenetic changes. Complex alternative splicing results in numerous transcripts from this gene, and we have identified novel transcripts containing a highly-conserved sequence within intron 4 ("gVC-In4"). In colorectal cancer cells, we demonstrate that treatment with insulin and insulin-like growth factors (IGF) repressed CRNDE nuclear transcripts, including those encompassing gVC-In4. These repressive effects were negated by use of inhibitors against either the PI3K/Akt/mTOR pathway or Raf/MAPK pathway, suggesting CRNDE is a downstream target of both signaling cascades. Expression array analyses revealed that siRNA-mediated knockdown of gVC-In4 transcripts affected the expression of many genes, which showed correlation with insulin/IGF signaling pathway components and responses, including glucose and lipid metabolism. Some of the genes are identical to those affected by insulin treatment in the same cell line. The results suggest that CRNDE expression promotes the metabolic changes by which cancer cells switch to aerobic glycolysis (Warburg effect). This is the first report of a lncRNA regulated by insulin/IGFs, and our findings indicate a role for CRNDE nuclear transcripts in regulating cellular metabolism which may correlate with their upregulation in colorectal cancer.
    Biochimica et Biophysica Acta 10/2013; 1843(2). DOI:10.1016/j.bbamcr.2013.10.016 · 4.66 Impact Factor
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    • "data to profile lncRNA expression across different types and grades of human gliomas. Of the 129 lncRNAs identified as differentially expressed in gliomas, the results consistently and convincingly identified CRNDE (both probesets) as the most highly upregulated lncRNA (32-fold; Zhang et al., 2012). This was the case for low and high grade astrocytomas (15-and 36-fold, respectively ) and oligodendrogliomas (8-and 29-fold, respectively), and CRNDE levels correlated positively with tumor grade in both types. "
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    ABSTRACT: CRNDE is the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding), a long non-coding RNA (lncRNA) gene that expresses multiple splice variants and displays a very tissue-specific pattern of expression. CRNDE was initially identified as a lncRNA whose expression is highly elevated in colorectal cancer, but it is also upregulated in many other solid tumors and in leukemias. Indeed, CRNDE is the most upregulated lncRNA in gliomas and here, as in other cancers, it is associated with a "stemness" signature. CRNDE is expressed in specific regions within the human and mouse brain; the mouse ortholog is high in induced pluripotent stem cells and increases further during neuronal differentiation. We suggest that CRNDE is a multifunctional lncRNA whose different splice forms provide specific functional scaffolds for regulatory complexes, such as the polycomb repressive complex 2 (PRC2) and CoREST chromatin-modifying complexes, which CRNDE helps pilot to target genes.
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