'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737

Oncogene

Volumn 26, Issue 27, 2007, Pages 3972-3979

  Lin, X ^a   Morgan Lappe, S ^a   Huang, X ^a   Li, L ^a   Zakula, D M ^a   Vernetti, L A ^a   Fesik, S W ^a   Shen, Y ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

ABT 737; Bcl XL; Mcl 1; Off target; Seed; siRNA

Indexed keywords

4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; ROSCOVITINE; SMALL INTERFERING RNA; SORAFENIB;

3' UNTRANSLATED REGION; ARTICLE; CANCER RESISTANCE; CONTROLLED STUDY; DRUG TARGETING; GENE LIBRARY; GENE SILENCING; GENETIC COMPLEMENTATION; HUMAN; HUMAN CELL; MOLECULAR MECHANICS; PHENOTYPE; PRIORITY JOURNAL; SCREENING;

3' UNTRANSLATED REGIONS; ANTINEOPLASTIC AGENTS; BASE SEQUENCE; BCL-X PROTEIN; BENZENESULFONATES; BIPHENYL COMPOUNDS; BLOTTING, WESTERN; CARCINOMA, SMALL CELL; CELL LINE, TUMOR; CELL SURVIVAL; DNA-BINDING PROTEINS; DRUG RESISTANCE, NEOPLASM; HUMANS; LUNG NEOPLASMS; NEOPLASM PROTEINS; NITROPHENOLS; PIPERAZINES; PROTO-ONCOGENE PROTEINS C-BCL-2; PURINES; PYRIDINES; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 2; RNA INTERFERENCE; RNA, SMALL INTERFERING; SULFONAMIDES; TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; ZINC FINGERS;

EID: 34249996230     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/sj.onc.1210166     Document Type: Article

References (14)

1. Birmingham A, Anderson EM, Reynolds A, Ilsley-Tyree D, Leake D, Fedorov Y et al. (2006). 30 UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat Methods 3: 199-204.
2. Danial NN, Korsmeyer SJ. (2004). Cell death: critical control points. Cell 116: 205-219.
3. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-811.
4. Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M et al. (2003). Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21: 635-637.
5. Kirkin V, Joos S, Zornig M. (2004). The role of Bcl-2 family members in tumorigenesis. Biochim Biophys Acta 1644: 229-249.
6. Kitada S, Zapata JM, Andreeff M, Reed JC. (2000). Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate antiapoptosis proteins in B-cell chronic lymphocytic leukemia. Blood 96: 393-397.
7. Lin X, Ruan X, Anderson MG, McDowell JA, Kroeger PE, Fesik SW et al. (2005). siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res 33: 4527-4535.
8. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA et al. (2005). An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435: 677-681.
9. Saxena S, Jonsson ZO, Dutta A. (2003). Small RNAs with imperfect match to endogenous mRNA repress translation. Implications for off-target activity of small inhibitory RNA in mammalian cells. J Biol Chem 278: 44312-44319.
10. Tijsterman M, Ketting RF, Plasterk RH. (2002). The genetics of RNA silencing. Annu Rev Genet 36: 489-519.
11. van de Donk NW, Kamphuis MM, van Kessel B, Lokhorst HM, Bloem AC. (2003). Inhibition of protein geranylgeranylation induces apoptosis in myeloma plasma cells by reducing Mcl-1 protein levels. Blood 102: 3354-3362.
12. Waterhouse PM, Wang MB, Lough T. (2001). Gene silencing as an adaptive defence against viruses. Nature 411: 834-842.
13. Yu C, Bruzek LM, Meng XW, Gores GJ, Carter CA, Kaufmann SH et al. (2005). The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006. Oncogene 24: 6861-6869.
14. Zeng Y, Yi R, Cullen BR. (2003). MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA 100: 9779-9784.