کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10802215 | 1055668 | 2014 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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![عکس صفحه اول مقاله: CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism](/preview/png/10802215.png)
چکیده انگلیسی
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 non-coding 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1843, Issue 2, February 2014, Pages 372-386
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1843, Issue 2, February 2014, Pages 372-386
نویسندگان
Blake C. Ellis, Lloyd D. Graham, Peter L. Molloy,