230 likes | 463 Views
MicroRNAs are Face-lifting The Diagnostic & Therapeutic Approaches For Liver Diseases in Egypt. By: Dr. Ahmed Ihab Abdelaziz , MD, PhD. Associate Professor of Molecular Medicine and Genetic Pathology . Head of the Molecular Pathology Unit & Research group. 1.
E N D
MicroRNAs are Face-liftingThe Diagnostic & Therapeutic Approaches For Liver Diseases in Egypt By: Dr. Ahmed Ihab Abdelaziz, MD, PhD. Associate Professor of Molecular Medicine and Genetic Pathology. Head of the Molecular Pathology Unit & Research group 1
Do All Patients Respond Equally ? Pharmacogenomics 2
Who is taking the control? It is about the function and not the size
MicroRNAs & its Epigenetic role in the Scenario of Liver Pathology • Host Response by Interferon release & interaction with the virus particles • Mailgnant Transformation of the hepatocytes (mitogenic signaling pathways) e.g.: Insulin-Like Growth factor II (IGFII) Role of miRNAs in:
Host Response to HCV Infection PKR MxA J Biol Chem, 2007
ISGs as predictors for EVR in HCV Genotype 4 Hamdi N, El-Akel W, El-Serafy M, Esmat G, Sarrazin C, and Abdelaziz AI. Intervirology, 2011
Expression of miR-146a and miR-155 in PBMCs of HCV g4 Patients This might indicate a functional inhibition in the pathway that might hinder the induction of miR-146a and miR-155
Impact of IFN & Imiquimod stimulation on miR-146a and miR-155 IFN stimulation induced the expression of miR-146a and miR-155 while imiquimod led to a down-regulation of both microRNAs HCV might interfere with miR-146a andmiR-155 expression at sites upstream of interferon release
Expression correlation of miR-146a and miR-155 El-Ekiaby N., Hamdi N., Negm M., Ahmed R., Zekri AR., Esmat G and Abdelaziz AI. FEBS Open Bio, 2012
IGF Signaling Pathway IGF-II IGF-I IGF-2R IR IGF-1R Extracellular Cytoplasm Shc Grb2 Decrease IGF-II Bioavailability IRS Sos RAS/RAF Stat-3 PI3K Akt/PKB Stat-3 MEK1/2 GSK-3 β Bad Caspase-9 Anti-apoptosis β -catenin ERK Nucleus Proliferation Anti-apoptosis Malignant Transformation Proliferation IGF signaling activation leads to Hyperproliferation
IGFf-II,MMP-9, and their tissue inhibitors in HCV prognosis to HCC El Tayebi HM, Salah W, El Sayed IH, Salam EM, Zekri AR, Zayed N, Salem ES, Esmat G, and Abdelaziz AI.Biomarkers. 2011
miR-615-5p overexpression alleviates the tumorigenic effects in HCV-progressed-HCC
Impact of forcing the expression of miR-615-5p on Cell Growth
Impact of forcing the expression of miR-615-5p on Cellular migration
Impact of forcing the expression of miR-615-5p on IGF-II expression
Binding Experiment of miR-615-5p on IGF-II expression . El Tayebi H.M.,Hosny K.A., Esmat G., Breuhahn K and Abdelaziz AI. FEBS letters, 2012
miR-17-5p, E2F-1 and c-MYC screening in liver tissues and their correlation analysis
Impact of miR-17–5p on E2F-1 and c-MYC transcript expression
Impact of miR-17-5p on cellular proliferation and viability;
Impact of miR-17-5p on cellular migration and anchorage-independent growth El Tayebi H.M., Omar K, Hegy S., El MaghrabiM., El Brolosy M., Hosny K.A., Esmat G. and Abdelaziz AI. BBRC, 2013