MicroRNAs (miRNAs) are small regulatory RNAs that act by blocking the translation and increasing the degradation of target transcripts. MiRNAs play a critical role in many biological processes including development and differentiation and many studies have shown that major changes in miRNA levels occur in cancer. Since miRNAs degrade target messages, we used this property to develop a novel computational method aimed at determining the actual biological activity of miRNAs using variations in gene expression. Using the method described here, we quantified miRNA activity in papillary thyroid carcinoma and breast cancer, and found a strong and distinctive signal of increased global miRNA activity, embedded in the pertaining gene expression measurements. Interestingly, we found that in these two cancers, miRNA activity is globally increased, and is associated with a global downregulation of miRNA target genes. This downreguation of miRNA regulated genes is particularly noticeable for genes carrying multiple target sites for miRNAs. Among the miRNA-repressed genes, we found a significant enrichment of known tumor suppressors, thereby suggesting that the increased miRNA activity was indeed tumorigenic.
机构:
Queens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North IrelandQueens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland
Arora, Amit
;
Simpson, David A. C.
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Queens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North IrelandQueens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
MIT, Dept Biol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Baek, Daehyun
;
Villen, Judit
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机构:
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Villen, Judit
;
Shin, Chanseok
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h-index: 0
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
MIT, Dept Biol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Shin, Chanseok
;
Camargo, Fernando D.
论文数: 0引用数: 0
h-index: 0
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Camargo, Fernando D.
;
Gygi, Steven P.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Gygi, Steven P.
;
Bartel, David P.
论文数: 0引用数: 0
h-index: 0
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
MIT, Dept Biol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
机构:
Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USAUniv So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA
Cheng, Chao
;
Li, Lei M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA
Univ So Calif, Dept Math, Los Angeles, CA USAUniv So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA
机构:
Queens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North IrelandQueens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland
Arora, Amit
;
Simpson, David A. C.
论文数: 0引用数: 0
h-index: 0
机构:
Queens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North IrelandQueens Univ Belfast, Royal Victoria Hosp, Inst Clin Sci, Ctr Vis Sci, Belfast BT12 6BA, Antrim, North Ireland
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
MIT, Dept Biol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Baek, Daehyun
;
Villen, Judit
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Villen, Judit
;
Shin, Chanseok
论文数: 0引用数: 0
h-index: 0
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
MIT, Dept Biol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Shin, Chanseok
;
Camargo, Fernando D.
论文数: 0引用数: 0
h-index: 0
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Camargo, Fernando D.
;
Gygi, Steven P.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Gygi, Steven P.
;
Bartel, David P.
论文数: 0引用数: 0
h-index: 0
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
MIT, Dept Biol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
机构:
Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USAUniv So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA
Cheng, Chao
;
Li, Lei M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA
Univ So Calif, Dept Math, Los Angeles, CA USAUniv So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA