The Role of miRNA in CancerSofia Mubarika2nd Symposium Biomolecular Update in CancerPadang 18 Mei 2013

Population Measures,Cancer Incidence and Mortality, Estimates : 2005-2010

Deaths due to Cancer

*miRNA in cancer

Breakthrough discoveries in miRNA biology van Rooij E Circulation Research 2011;108:219-234Copyright American Heart AssociationEndogenously expressed - small Non-coding RNA- function as post-transcriptional regulators of gene expression- discovered in 1993 by Victor Ambros, Rosalind Lee and Rhonda Feinbaum - gene lin-14

Micro RNAs Regulate Cell Growth and Death

Defining the functional cancer genome using RNAi analysis and screening

Defining the functional cancer genome using RNAi analysis and screening

DNACytogenetic , Sequence GWAS , Copy noRNAmRNA/miRNA expressionProteinAntibody Mass SpecGENE SPECIFIC RNAi ANALYSIS AND SCREENING

miRNA play a role : regulating gene expression, phenotype of tumor cells, proliferation, cell cycle progression, survival, invasion, cell differentiation and morphogenesis miRNA is small and stable molecules Biology targetted therapy:Drug Resistence related proteinAngiogenesisTumor stem cells Cancer replacement therapy Promising Biomarker

http://www.cancer.gov

Gene regulationdiscovermagazine.com

miRNA is short nucleotide (19-24 bases), non coding RNA. (Cho et al, 2011). 1993,C.elegansRelease miRBase2005,Pasien CLL, delesi 13q14, miR 15a dan 16-1Goal

Biogenesis of miRNAGarzon, 2006, Trends in Molecular Medicine Vol 12 No 12

Yang et al, 2013

miRNA development research

(Corcoran et al., 2011)

Shenouda & Alahari, 2009

miRNA correlated with specified cancerLi et al., 2010

MCF-7MCF-7/DOXImunocytochemistry, Immunofloresence, dan Western BlotEfflux Mechanism

P-glycoprotein (P-gp) is a protein that is coded by MDR1 gene (Mechetner et al., 1998).

Restoration of miR 451 in sel MCF7/Dox shows incerase sensitivity to Doxorubicin.Kovalchuck et al., 2008

miRNA regulate drug resistance

ConclusionMiRNA is small molecule but big functionsEvidences : miRNA play a very important role in carcinogenesis and drug sensitivity of tumor cells.Current data : miRNA can be categorized as oncogenes and tumor suppressor genes based on its targetsmiRNA are promising cancer biomarkers and are potential as target therapiesmiRNA is a very stable molecules

Breakthrough discoveries in miRNA biology. Time line indicating seminal discoveries in miRNA biology with a special focus on the cardiovascular field.Expression of P-gp in theMCF-7 and MCF-7/DOX human breastadenocarcinoma cells as detected byimmunocytochemistry (A and C), immunofluorescence(B and D), and immunoblotting(E).*