causes and consequences of microrna dysregulation in cancer hulusi onur kuzucu - 2007103937
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Causes and consequences of microRNA dysregulation in cancer
Hulusi Onur Kuzucu - 2007103937
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What are miRNA? 1993, Victor Ambros Small non-protein-coding RNA Undergo several modifications Incorporated into RISC Negative regulators; inhibit translation,
promote degredation
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miRNA as Cancer genes Chronic Lymphocytic Leukaemia (CLL) Alterations in 13q14, non-protein-coding
region miR-15a & miR-16-1 General alterations of miRNA genes Dysregulation of miRNA expression
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miRNA as Tumor suppressors Heterogeneity Loss of miR-15a & miR-16-1 in indolent CLLs Loss of miRNA at 11q23 and TP53, leading to
aggressive cells No rigid sequence of genetic events Mutations affect miRNA function
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miRNA as Oncogenes Overexpression of miRNA miR-155 – 21q23 Amplification in various BCL miR-17-92 cluster – C13orf25 Promote proliferation Transactivation by MYC Affects E2F transcription factors Downregulates PTEN, p21, BIM
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miRNA dysregulation by transcription factors miR-34 family and p53 TS – positive ERα tumors & miR-221, miR-222 – negative Dysregulated miRNA genes, targets and
mechanism of action
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miRNA in Cancer epigenetics Methylation of CpG islands, miR-127 miR-29 & DNMTs
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Conclusion miRNA therapy Different methods to introduce miRNAs Use of miR-15a, miR-16-1 and miR-29 on
cancer cells, reversal of changes Focusing on miRNA dysregulation Identifying miRNAs and their targets Shifting from conventional chemotherapy to
targeted therapies
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Thank you References:
Carlo M. Croce
Causes and consequences of microRNA dysregulation in cancer
Nature Reviews Genetics: October 2009 Vol 10 No 10 p704 | doi:10.1038/nrg2634
Lee, R. C., Feinbaum, R. L. & Ambros, V.
The C. elegans heterochronic gene lin-4 encodes small RNAs with anti-sense complementarity to lin-14.
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O’Donnell, K. A. et al.
c-Myc-regulated microRNAs modulate E2F1 expression.
Nature 435, 839–843 (2005).
Raver-Shapira, N. et al.
Transcriptional activation of miR-34a contributes to p53-mediated apoptosis.
Mol. Cell 26, 731–743 (2007).
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MicroRNA expression signature of human solid tumors defines cancer gene targets.
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Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.
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