Causes and consequences of microRNA dysregulation in cancer

Hulusi Onur Kuzucu - 2007103937

What are miRNA? 1993, Victor Ambros Small non-protein-coding RNA Undergo several modifications Incorporated into RISC Negative regulators; inhibit translation,

promote degredation

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

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

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

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

miRNA in Cancer epigenetics Methylation of CpG islands, miR-127 miR-29 & DNMTs

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

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

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