Genome-scale microRNA and small interfering RNA screens identify small RNA modulators of TRAIL-induced apoptosis pathway.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to death receptors 4/5 and selectively induces caspase-dependent apoptosis. The RNA interference screening approach has led to the discovery and characterization of several TRAIL pathway components in human cells. Here, libraries of synthetic small interfering RNA (siRNA) and microRNAs (miRNA) were used to probe the TRAIL pathway. In addition to known genes, siRNAs targeting CDK4, PTGS1, ALG2, CLCN3, IRAK4, and MAP3K8 altered TRAIL-induced caspase-3 activation responses. Introduction of the miRNAs let-7c, mir-10a, mir-144, mir-150, mir-155, and mir-193 also affected the activation of the caspase cascade. Putative targets of these endogenous miRNAs included genes encoding death receptors, caspases, and other apoptosis-related genes. Among the novel genes revealed in the screen, CDK4 was selected for further characterization. CDK4 was the only member of the cyclin-dependent kinase gene family that bore a unique function in apoptotic signal transduction.

[1]  George A. Calin,et al.  A MicroRNA Signature of Hypoxia , 2006, Molecular and Cellular Biology.

[2]  S. Cohen,et al.  The Hippo Pathway Regulates the bantam microRNA to Control Cell Proliferation and Apoptosis in Drosophila , 2006, Cell.

[3]  G. Shapiro,et al.  Cyclin-dependent kinase pathways as targets for cancer treatment. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  C. Croce,et al.  Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. , 2006, Seminars in oncology.

[5]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[6]  Yan Geng,et al.  Requirement for CDK4 kinase function in breast cancer. , 2006, Cancer cell.

[7]  Stefano Volinia,et al.  Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Phillip D Zamore,et al.  microPrimer: the biogenesis and function of microRNA , 2005, Development.

[9]  C. Croce,et al.  miR-15 and miR-16 induce apoptosis by targeting BCL2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  K. Kelnar,et al.  High-throughput RNAi screening in vitro: from cell lines to primary cells. , 2005, RNA.

[11]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[12]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[13]  Peizhang Xu,et al.  MicroRNAs and the regulation of cell death. , 2004, Trends in genetics : TIG.

[14]  Q. Deveraux,et al.  Differential regulation of the TRAIL death receptors DR4 and DR5 by the signal recognition particle. , 2004, Molecular biology of the cell.

[15]  C. Echeverri,et al.  Oncology studies using siRNA libraries: the dawn of RNAi-based genomics , 2004, Oncogene.

[16]  B. Williams,et al.  RNA interference and double-stranded-RNA-activated pathways. , 2004, Biochemical Society transactions.

[17]  G. Hannon,et al.  RNA-interference-based functional genomics in mammalian cells: reverse genetics coming of age , 2004, Oncogene.

[18]  M. Smyth,et al.  TRAIL and its receptors as targets for cancer therapy , 2004, Cancer science.

[19]  R. Giegerich,et al.  Fast and effective prediction of microRNA/target duplexes. , 2004, RNA.

[20]  Pierre Dubus,et al.  Mammalian Cells Cycle without the D-Type Cyclin-Dependent Kinases Cdk4 and Cdk6 , 2004, Cell.

[21]  Tak W. Mak,et al.  Pathways of apoptotic and non-apoptotic death in tumour cells , 2004, Nature Reviews Cancer.

[22]  Sergey E Ilyin,et al.  High-Throughput siRNA-Based Functional Target Validation , 2004, Journal of biomolecular screening.

[23]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[24]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[25]  Michael Z Michael,et al.  Reduced accumulation of specific microRNAs in colorectal neoplasia. , 2003, Molecular cancer research : MCR.

[26]  Serge Batalov,et al.  Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. , 2003, Molecular cell.

[27]  浅沼 広子,et al.  High-Throughput な迅速凍結標本の作製 , 2002 .

[28]  A. Carnero,et al.  Targeting the cell cycle for cancer therapy , 2002, British Journal of Cancer.

[29]  F. Slack,et al.  Control of developmental timing by small temporal RNAs: a paradigm for RNA‐mediated regulation of gene expression , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[30]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

[31]  M. Smyth,et al.  Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells , 2001, Nature Medicine.

[32]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[33]  P. Pandolfi,et al.  Targeted Disruption of CDK4 Delays Cell Cycle Entry with Enhanced p27Kip1 Activity , 1999, Molecular and Cellular Biology.

[34]  M. Nau,et al.  Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. , 1999, Cancer research.

[35]  V. Dixit,et al.  Death receptors: signaling and modulation. , 1998, Science.

[36]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[37]  L. Hood,et al.  Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. , 1997, Immunity.

[38]  Arul M. Chinnaiyan,et al.  The Receptor for the Cytotoxic Ligand TRAIL , 1997, Science.

[39]  M. Raff,et al.  Programmed Cell Death in Animal Development , 1997, Cell.

[40]  G. Peters,et al.  Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. , 1996, Advances in cancer research.

[41]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[42]  K. Tracey,et al.  Tumor necrosis factor, other cytokines and disease. , 1993, Annual review of cell biology.

[43]  L. Tsai,et al.  A family of human cdc2‐related protein kinases. , 1992, The EMBO journal.

[44]  H. Loetscher,et al.  Tumor necrosis factor receptors-structure and function , 1992, Immunologic research.