MicroRNA-21 targets tumor suppressor genes in invasion and metastasis.pptVIP

MicroRNA-21 targets tumor suppressor genes in invasion and metastasis MicroRNAs (miRNAs) First discovered : lin-4 let-7 in C.elegans Naturally occurring small non-coding RNAs Mature miRNA : ≈ 22 nucleotides Post-transcriptional control (cytoplasm) Micro RNAs ? Short interfering RNAs Targeting : mRNA miRNA : inhibit mRNA translation si RNA : cause mRNA degradation Pri-miRNA (primary miRNA) Excised intron 3’-UTR of pre-mRNAs Imperfect-pairing ≈70 nt Drosha : RNase for DS-RNA DGCR8: Binding protein Exporting 5 : through NPC Dicer : RNase for DS-RNA TRBP : Binding protien DS-miRNA : ≈ 21-23 nt (unpaired 3’-nucleotides) RISC : RNA-induced silencing complex (miRNA + Argonuate protein) MicroRNA (miRNA) Target RNA : 3’-UTR (untranslated region) Imperfect base-pairing Targeting Cluster of genes One miRNA ≈ more than 100 genes Estimated 1/3 human genes regulated by ≈ 1,000 miRNA Inhibition of mRNA requiring  Binding of two or more RISC Express only  In specific cell types and time miRNAs Regulating : Proliferation  Differentiation  Apoptosis …… Deregulation of miRNAs …… Affect normal cell growth development Leading to variety cause of disorder Including Human malignancies miRNA in human malignancies Tumor-suppresor miRNA Oncogenic miRNA miRNA involving diverse cellular processes…… mir-21 : oncogenic microRNA Promote MCF-7 cell line in vitro and in vivo Correlated with tumor growth and metastasis in pancreatic cancer specimen Suppress expression of tumor suppressor genes PTEN (Phosphatase and TENsin homolog) TPM1 (Trpomyosin 1) ? implicate in cell migration and invasion mir-21 may involve in invasion metastasis But…… how ? Hypothesis : mir-21 regulate invasion and metastasis, at least in part, by targeting metastasis-related tumor suppressor genes such as  TPM1, PDCD4 and maspin # PDCD4 : Programmed C