Elevated Mirc1/Mir17-92 cluster expression negatively regulates autophagy and CFTR (cystic fibrosis transmembrane conductance regulator) function in CF macrophages

Autophagy

Volumn 12, Issue 11, 2016, Pages 2026-2037

  Tazi, Mia F ^a,b   Dakhlallah, Duaa A ^b   Caution, Kyle ^a,b   Gerber, Madelyn M ^a,b   Chang, Sheng Wei ^a,b   Khalil, Hany ^c   Kopp, Benjamin T ^d   Ahmed, Amr E ^a,b   Krause, Kathrin ^a,b   Davis, Ian ^a   Marsh, Clay ^b   Lovett Racke, Amy E ^a   Schlesinger, Larry S ^a,b   Cormet Boyaka, Estelle ^a,b   Amer, Amal O ^a,b  

^a OHIO STATE UNIVERSITY   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c UNIVERSITY OF SADAT CITY   (Egypt)

^d NATIONWIDE CHILDREN S HOSPITAL   (United States)

Author keywords

autophagy; Burkholderia cenocepacia; CFTR function; cystic fibrosis; macrophages; Mirc1 Mir17 92 cluster

Indexed keywords

3 METHYLADENINE; ATG12 PROTEIN; ATG16L1 PROTEIN; ATG4 PROTEIN; ATG4D PROTEIN; ATG7 PROTEIN; AUTOPHAGY PROTEIN 5; BECLIN 1; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; LC3 PROTEIN; MICRORNA; MICRORNA 1; MICRORNA 101; MICRORNA 17; MICRORNA 20A; MICRORNA 92; PROTEIN; RAB5A PROTEIN; STMN1 PROTEIN; UNCLASSIFIED DRUG; 3' UNTRANSLATED REGION; ANTAGOMIR; AUTOPHAGY RELATED PROTEIN; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR DELTA F508; MIRN17-92 MICRORNA, MOUSE;

3' UNTRANSLATED REGION; 3T3 CELL LINE; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; AUTOPHAGY; BACTERIAL CLEARANCE; BACTERIAL LOAD; BURKHOLDERIA CENOCEPACIA; CONFOCAL MICROSCOPY; CONTROLLED STUDY; CYSTIC FIBROSIS; DOWN REGULATION; GENE EXPRESSION; GENE FUNCTION; GENE TARGETING; GENETIC TRANSFECTION; HOST RESISTANCE; HUMAN; HUMAN CELL; IN VITRO STUDY; LUCIFERASE ASSAY; LUNG HOMOGENATE; MACROPHAGE; MONOCYTE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; UPREGULATION; ANIMAL; C57BL MOUSE; CELL CULTURE; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HOMOZYGOTE; LUNG; METABOLISM; MICROBIOLOGY; NIH 3T3 CELL LINE; PATHOLOGY; PHYSIOLOGY;

3' UNTRANSLATED REGIONS; ANIMALS; ANTAGOMIRS; AUTOPHAGY; AUTOPHAGY-RELATED PROTEINS; BURKHOLDERIA CENOCEPACIA; CELLS, CULTURED; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GENE EXPRESSION REGULATION; HOMOZYGOTE; LUNG; MACROPHAGES; MICE; MICE, INBRED C57BL; MICRORNAS; NIH 3T3 CELLS;

EID: 84994086225     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.1080/15548627.2016.1217370     Document Type: Article

References (70)

1. T.Treiber, N.Treiber, G.Meister. Regulation of microRNA biogenesis and function. Thromb Haemost 2012; 107:605-10; PMID:22318703; http://dx.doi.org/10.1160/TH11-12-0836
2. Q.Jiang, J.F.Engelhardt. Cellular heterogeneity of CFTR expression and function in the lung:implications for gene therapy of cystic fibrosis. Eur J Hum Genet 1998; 6:12-31; PMID:9781011; http://dx.doi.org/10.1038/sj.ejhg.5200158
3. M.J.Welsh, G.M.Denning, L.S.Ostedgaard, M.P.Anderson. Dysfunction of CFTR bearing the delta F508 mutation. J Cell Sci Suppl 1993; 17:235-9; PMID:7511616; http://dx.doi.org/10.1242/jcs.1993.Supplement_17.33
4. R.D.Coakley, B.R.Grubb, A.M.Paradiso, J.T.Gatzy, L.G.Johnson, S.M.Kreda, W.K.O'Neal, R.C.Boucher. Abnormal surface liquid pH regulation by cultured cystic fibrosis bronchial epithelium. Proc Natl Acad Sci U S A 2003; 100:16083-8; PMID:14668433; http://dx.doi.org/10.1073/pnas.2634339100
5. S.Blouquit, A.Regnier, L.Dannhoffer, C.Fermanian, E.Naline, R.Boucher, T.Chinet. Ion and fluid transport properties of small airways in cystic fibrosis. Am J Respir Crit Care Med 2006; 174:299-305; PMID:16645176; http://dx.doi.org/10.1164/rccm.200506-987OC
6. E.M.Bruscia, T.L.Bonfield. Innate and Adaptive Immunity in Cystic Fibrosis. Clin Chest Med 2016; 37:17-29; PMID:26857765; http://dx.doi.org/10.1016/j.ccm.2015.11.010
7. D.Hartl, A.Gaggar, E.Bruscia, A.Hector, V.Marcos, A.Jung, C.Greene, G.McElvaney, M.Mall, G.Döring. Innate immunity in cystic fibrosis lung disease. J Cyst Fibros 2012; 11:363-82; PMID:22917571; http://dx.doi.org/10.1016/j.jcf.2012.07.003
8. G.Doring, E.Gulbins. Cystic fibrosis and innate immunity:how chloride channel mutations provoke lung disease. Cell Microbiol 2009; 11:208-16; PMID:19068098; http://dx.doi.org/10.1111/j.1462-5822.2008.01271.x
9. G.B.Pier. Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections. Proc Natl Acad Sci U S A 2000; 97:8822-8; PMID:10922041; http://dx.doi.org/10.1073/pnas.97.16.8822
10. B.A.Abdulrahman, A.A.Khweek, A.Akhter, K.Caution, S.Kotrange, D.H.Abdelaziz, C.Newland, R.Rosales-Reyes, B.Kopp, K.McCoy, et al. Autophagy stimulation by rapamycin suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of cystic fibrosis. Autophagy 2011; 7:1359-70; PMID:21997369; http://dx.doi.org/10.4161/auto.7.11.17660
11. B.A.Abdulrahman, A.A.Khweek, A.Akhter, K.Caution, M.Tazi, H.Hassan, Y.Zhang, P.D.Rowland, S.Malhotra, F.Aeffner, et al. Depletion of the ubiquitin-binding adaptor molecule SQSTM1/p62 from macrophages harboring cftr DeltaF508 mutation improves the delivery of Burkholderia cenocepacia to the autophagic machinery. J Biol Chem 2013; 288:2049-58; PMID:23148214; http://dx.doi.org/10.1074/jbc.M112.411728
12. P.J.French, J.H.van Doorninck, R.H.Peters, E.Verbeek, N.A.Ameen, C.R.Marino, H.R.de Jonge, J.Bijman, B.J.Scholte. A delta F508 mutation in mouse cystic fibrosis transmembrane conductance regulator results in a temperature-sensitive processing defect in vivo. J Clin Invest 1996; 98:1304-12; PMID:8823295; http://dx.doi.org/10.1172/JCI118917
13. P.Gomes-Alves, S.Neves, A.V.Coelho, D.Penque. Low temperature restoring effect on F508del-CFTR misprocessing:A proteomic approach. J Proteomics 2009; 73:218-30; PMID:19775599; http://dx.doi.org/10.1016/j.jprot.2009.09.001
14. C.Hogenauer, C.A.Santa Ana, J.L.Porter, M.Millard, A.Gelfand, R.L.Rosenblatt, C.B.Prestidge, J.S.Fordtran. Active intestinal chloride secretion in human carriers of cystic fibrosis mutations:an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion. Am J Hum Genet 2000; 67:1422-7; PMID:11055897; http://dx.doi.org/10.1086/316911
15. L.Zhang, B.Button, S.E.Gabriel, S.Burkett, Y.Yan, M.H.Skiadopoulos, Y.L.Dang, L.N.Vogel, T.McKay, A.Mengos, et al. CFTR delivery to 25% of surface epithelial cells restores normal rates of mucus transport to human cystic fibrosis airway epithelium. PLoS Biol 2009; 7:e1000155; PMID:19621064; http://dx.doi.org/10.1371/journal.pbio.1000155
16. I.K.Oglesby, S.H.Chotirmall, N.G.McElvaney, C.M.Greene. Regulation of cystic fibrosis transmembrane conductance regulator by microRNA-145, −223, and −494 is altered in DeltaF508 cystic fibrosis airway epithelium. J Immunol 2013; 190:3354-62; PMID:23436935; http://dx.doi.org/10.4049/jimmunol.1202960
17. D.J.Klionsky. The molecular machinery of autophagy and its role in physiology and disease. Semin Cell Dev Biol 2010; 21:663; PMID:20430106; http://dx.doi.org/10.1016/j.semcdb.2010.04.005
18. K.Assani, M.F.Tazi, A.O.Amer, B.T.Kopp. IFN-gamma stimulates autophagy-mediated clearance of Burkholderia cenocepacia in human cystic fibrosis macrophages. PLoS One 2014; 9:e96681; PMID:24798083; http://dx.doi.org/10.1371/journal.pone.0096681
19. A.Luciani, V.R.Villella, S.Esposito, N.Brunetti-Pierri, D.L.Medina, C.Settembre, M.Gavina, V.Raia, A.Ballabio, L.Maiuri. Cystic fibrosis:a disorder with defective autophagy. Autophagy 2011; 7:104-6; PMID:21048426; http://dx.doi.org/10.4161/auto.7.1.13987
20. Z.Yang, D.J.Klionsky. Eaten alive:a history of macroautophagy. Nat Cell Biol 2010; 12:814-22; PMID:20811353; http://dx.doi.org/10.1038/ncb0910-814
21. G.Bjorkoy, T.Lamark, T.Johansen. p62/SQSTM1:a missing link between protein aggregates and the autophagy machinery. Autophagy 2006; 2:138-9; PMID:16874037; http://dx.doi.org/10.4161/auto.2.2.2405
22. N.Mizushima, T.Noda, T.Yoshimori, Y.Tanaka, T.Ishii, M.D.George, D.J.Klionsky, M.Ohsumi, Y.Ohsumi. A protein conjugation system essential for autophagy. Nature 1998; 395:395-8; PMID:9759731; http://dx.doi.org/10.1038/26506
23. D.J.Klionsky, S.D.Emr. Autophagy as a regulated pathway of cellular degradation. Science 2000; 290:1717-21; PMID:11099404; http://dx.doi.org/10.1126/science.290.5497.1717
24. H.A.D.Abdelaziz, H.Khalil, E.Cormet-Boyaka, A.Amer. The cooperation between the autophagy machinery and the inflammasome to implement an appropriate innate immune response:Do they regulate each other? Immunological Reviews 2015; 265(1):194-204; PMID:25879294; http://dx.doi.org/10.1111/imr.12288
25. S.Ramachandran, P.H.Karp, P.Jiang, L.S.Ostedgaard, A.E.Walz, J.T.Fisher, S.Keshavjee, K.A.Lennox, A.M.Jacobi, S.D.Rose, et al. A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator. Proc Natl Acad Sci U S A 2012; 109:13362-7; PMID:22853952; http://dx.doi.org/10.1073/pnas.1210906109
26. M.Bazett, A.Paun, C.K.Haston. MicroRNA profiling of cystic fibrosis intestinal disease in mice. Mol Genet Metab 2011; 103:38-43; PMID:21333573; http://dx.doi.org/10.1016/j.ymgme.2011.01.012
27. J.T.Mendell. Miriad roles for the Mir17-92 cluster in development and disease. Cell 2008; 133:217-22; PMID:18423194; http://dx.doi.org/10.1016/j.cell.2008.04.001
28. D.Dakhlallah, K.Batte, Y.Wang, C.Z.CanteMirStone, P.Yan, G.Nuovo, A.Mikhail, C.L.Hitchcock, V.P.Wright, S.P.Nana-Sinkam, et al. Epigenetic Regulation of Mir17∼92 Contributes to the Pathogenesis of Pulmonary Fibrosis. Am J Respir Crit Care Med 2013; 187:397-405; PMID:23306545; http://dx.doi.org/10.1164/rccm.201205-0888OC
29. B.D.Aguda, Y.Kim, M.G.Piper-Hunter, A.Friedman, C.B.Marsh. MicroRNA regulation of a cancer network:consequences of the feedback loops involving Mir17-92, E2F, and Myc. Proc Natl Acad Sci U S A 2008; 105:19678-83; PMID:19066217; http://dx.doi.org/10.1073/pnas.0811166106
30. S.P.Nana-Sinkam, T.Karsies, B.Riscili, M.Ezzie, M.Piper. Lung microRNA:from development to disease. Expert Rev Respir Med 2009; 3:373-85; PMID:20477329; http://dx.doi.org/10.1586/ers.09.30
31. A.Bonauer, S.Dimmeler. The microRNA-17-92 cluster:still a Miracle? Cell Cycle 2009; 8:3866-73; PMID:19887902; http://dx.doi.org/10.4161/cc.8.23.9994
32. L.Chen, C.Li, R.Zhang, X.Gao, X.Qu, M.Zhao, C.Qiao, J.Xu, J.Li. Mir17-92 cluster microRNAs confers tumorigenicity in multiple myeloma. Cancer Lett 2011; 309:62-70; PMID:21664042; http://dx.doi.org/10.1016/j.canlet.2011.05.017
33. J.Grillari, M.Hackl, R.Grillari-Voglauer. Mir17-92 cluster:ups and downs in cancer and aging. Biogerontology 2010; 11:501-6; PMID:20437201; http://dx.doi.org/10.1007/s10522-010-9272-9
34. Y.Hayashita, H.Osada, Y.Tatematsu, H.Yamada, K.Yanagisawa, S.Tomida, Y.Yatabe, K.Kawahara, Y.Sekido, T.Takahashi. A polycistronic microRNA cluster, Mir17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65:9628-32; PMID:16266980; http://dx.doi.org/10.1158/0008-5472.CAN-05-2352
35. L.B.Frankel, J.Wen, M.Lees, M.Hoyer-Hansen, T.Farkas, A.Krogh, M.Jäättelä, A.H.Lund. microRNA-101 is a potent inhibitor of autophagy. EMBO J 2011; 30:4628-41; PMID:21915098; http://dx.doi.org/10.1038/emboj.2011.331
36. S.Chakraborty, S.Mehtab, A.Patwardhan, Y.Krishnan. Pri-Mir17-92a transcript folds into a tertiary structure and autoregulates its processing. RNA 2012; 18:1014-28; PMID:22450760; http://dx.doi.org/10.1261/rna.031039.111
37. I.Sermet-Gaudelus, B.Vallee, I.Urbin, T.Torossi, R.Marianovski, A.Fajac, M.N.Feuillet, J.L.Bresson, G.Lenoir, J.F.Bernaudin, et al. Normal function of the cystic fibrosis conductance regulator protein can be associated with homozygous (Delta)F508 mutation. Pediatr Res 2002; 52:628-35; PMID:12409506
38. J.Xie, M.L.Drumm, J.Ma, P.B.Davis. Intracellular loop between transmembrane segments IV and V of cystic fibrosis transmembrane conductance regulator is involved in regulation of chloride channel conductance state. J Biol Chem 1995; 270:28084-91; PMID:7499295; http://dx.doi.org/10.1074/jbc.270.47.28084
39. R.D.Junkins, C.McCormick, T.J.Lin. The emerging potential of autophagy-based therapies in the treatment of cystic fibrosis lung infections. Autophagy 2014; 10:538-47; PMID:24434788; http://dx.doi.org/10.4161/auto.27750
40. A.Luciani, V.R.Villella, S.Esposito, N.Brunetti-Pierri, D.Medina, C.Settembre, M.Gavina, L.Pulze, I.Giardino, M.Pettoello-Mantovani, et al. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat Cell Biol 2010; 12:863-75; PMID:20711182; http://dx.doi.org/10.1038/ncb2090
41. M.L.Mayer, C.J.Blohmke, R.Falsafi, C.D.Fjell, L.Madera, S.E.Turvey, R.E.Hancock. Rescue of dysfunctional autophagy attenuates hyperinflammatory responses from cystic fibrosis cells. J Immunol 2013; 190:1227-38; PMID:23264659; http://dx.doi.org/10.4049/jimmunol.1201404
42. B.T.Kopp, B.A.Abdulrahman, A.A.Khweek, S.B.Kumar, A.Akhter, R.Montione, M.F.Tazi, K.Caution, K.McCoy, A.O.Amer. Exaggerated inflammatory responses mediated by Burkholderia cenocepacia in human macrophages derived from Cystic fibrosis patients. Biochem Biophys Res Commun 2012; 424:221-7; PMID:22728038; http://dx.doi.org/10.1016/j.bbrc.2012.06.066
43. V.Witko-Sarsat, I.Sermet-Gaudelus, G.Lenoir, B.Descamps-Latscha. Inflammation and CFTR:might neutrophils be the key in cystic fibrosis? Mediators Inflamm 1999; 8:7-11; PMID:10704083; http://dx.doi.org/10.1080/09629359990658
44. Y.Zhou, K.Song, R.G.Painter, M.Aiken, J.Reiser, B.A.Stanton, W.M.Nauseef, G.Wang. Cystic fibrosis transmembrane conductance regulator recruitment to phagosomes in neutrophils. J Innate Immun 2013; 5:219-30; PMID:23486169; http://dx.doi.org/10.1159/000346568
45. C.W.Wang, D.J.Klionsky. The molecular mechanism of autophagy. Mol Med 2003; 9:65-76; PMID:12865942
46. A.O.Amer, M.S.Swanson. Autophagy is an immediate macrophage response to Legionella pneumophila. Cell Microbiol 2005; 7:765-78; PMID:15888080; http://dx.doi.org/10.1111/j.1462-5822.2005.00509.x
47. H.Khalil, M.Tazi, K.Caution, A.Ahmed, A.Kanneganti, K.Assani, B.Kopp, C.Marsh, D.Dakhlallah, A.O.Amer. Aging is associated with hypermethylation of autophagy genes in macrophages. Epigenetics 2016; 11:381-8; PMID:26909551
48. A.Luciani, V.R.Villella, S.Esposito, M.Gavina, I.Russo, M.Silano, S.Guido, M.Pettoello-Mantovani, R.Carnuccio, B.Scholte, et al. Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on DeltaF508 cystic fibrosis transmembrane conductance regulator. Autophagy 2012; 8:1657-72; PMID:22874563; http://dx.doi.org/10.4161/auto.21483
49. S.Huang, P.J.Houghton. Inhibitors of mammalian target of rapamycin as novel antitumor agents:from bench to clinic. Curr Opin Investig Drugs 2002; 3:295-304; PMID:12020063
50. D.De Stefano, V.R.Villella, S.Esposito, A.Tosco, A.Sepe, F.De Gregorio, L.Salvadori, R.Grassia, C.A.Leone, G.De Rosa, et al. Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation. Autophagy 2014; 10:2053-74; PMID:25350163; http://dx.doi.org/10.4161/15548627.2014.973737
51. V.R.Villella, S.Esposito, M.C.Maiuri, V.Raia, G.Kroemer, L.Maiuri. Towards a rational combination therapy of cystic fibrosis:How cystamine restores the stability of mutant CFTR. Autophagy 2013; 9:1431-4; PMID:23800975; http://dx.doi.org/10.4161/auto.25517
52. A.Ventura, A.G.Young, M.M.Winslow, L.Lintault, A.Meissner, S.J.Erkeland, J.Newman, R.T.Bronson, D.Crowley, J.R.Stone, et al. Targeted deletion reveals essential and overlapping functions of the Mir17 through 92 family of MirNA clusters. Cell 2008; 132:875-86; PMID:18329372; http://dx.doi.org/10.1016/j.cell.2008.02.019
53. A.E.Gillen, N.Gosalia, S.H.Leir, A.Harris. MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene. Biochem J 2011; 438:25-32; PMID:21689072; http://dx.doi.org/10.1042/BJ20110672
54. F.G.Bowling, J.J.McGill, R.W.Shepherd, D.M.Danks. Screening for cystic fibrosis:use of delta F508 mutation. Lancet 1990; 335:925-6; PMID:1970022; http://dx.doi.org/10.1016/0140-6736(90)90534-C
55. M.R.Morris, M.M.Pereira, M.B.Hallett, M.A.McPherson, R.L.Dormer. Cellular localisation of the most common mutant form of the CF gene protein, delta F508-CFTR. Biochem Soc Trans 1998; 26:S293; PMID:9766012; http://dx.doi.org/10.1042/bst026s293
56. S.Patel, I.P.Sinha, K.Dwan, C.Echevarria, M.Schechter, K.W.Southern. Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis. Cochrane Database Syst Rev 2015; 3:CD009841; PMID:25811419
57. K.Kuk, J.L.Taylor-Cousar. Lumacaftor and ivacaftor in the management of patients with cystic fibrosis:current evidence and future prospects. Ther Adv Respir Dis 2015; 9:313-26; PMID:26416827; http://dx.doi.org/10.1177/1753465815601934
58. J.C.Cohen, L.K.Lundblad, J.H.Bates, M.Levitzky, J.E.Larson. The “Goldilocks effect” in cystic fibrosis:identification of a lung phenotype in the cftr knockout and heterozygous mouse. BMC Genet 2004; 5:21; PMID:15279681; http://dx.doi.org/10.1186/1471-2156-5-21
59. S.E.Gabriel, K.N.Brigman, B.H.Koller, R.C.Boucher, M.J.Stutts. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science 1994; 266:107-9; PMID:7524148; http://dx.doi.org/10.1126/science.7524148
60. C.Guilbault, Z.Saeed, G.P.Downey, D.Radzioch. Cystic fibrosis mouse models. Am J Respir Cell Mol Biol 2007; 36:1-7; PMID:16888286; http://dx.doi.org/10.1165/rcmb.2006-0184TR
61. L.G.Johnson, J.C.Olsen, B.Sarkadi, K.L.Moore, R.Swanstrom, R.C.Boucher. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat Genet 1992; 2:21-5; PMID:1284642; http://dx.doi.org/10.1038/ng0992-21
62. P.Maisonneuve, B.C.Marshall, E.A.Knapp, A.B.Lowenfels. Cancer risk in cystic fibrosis:a 20-year nationwide study from the United States. J Natl Cancer Inst 2013; 105:122-9; PMID:23178438; http://dx.doi.org/10.1093/jnci/djs481
63. P.Maisonneuve, B.C.Marshall, A.B.Lowenfels. Risk of pancreatic cancer in patients with cystic fibrosis. Gut 2007; 56:1327-8; PMID:17698876; http://dx.doi.org/10.1136/gut.2007.125278
64. V.Olive, I.Jiang, L.He. Mir17-92, a cluster of MirNAs in the midst of the cancer network. Int J Biochem Cell Biol 2010; 42:1348-54; PMID:20227518; http://dx.doi.org/10.1016/j.biocel.2010.03.004
65. R.A.Padua, N.Warren, D.Grimshaw, M.Smith, C.Lewis, J.Whittaker, P.Laidler, P.Wright, A.Douglas-Jones, P.Fenaux, et al. The cystic fibrosis delta F508 gene mutation and cancer. Hum Mutat 1997; 10:45-8; PMID:9222759; http://dx.doi.org/10.1002/(SICI)1098-1004(1997)10:1%3c45::AID-HUMU6%3e3.0.CO;2-L
66. J.P.Neglia, S.C.FitzSimmons, P.Maisonneuve, M.H.Schoni, F.Schoni-Affolter, M.Corey, A.B.Lowenfels. The risk of cancer among patients with cystic fibrosis. Cystic Fibrosis and Cancer Study Group. N Engl J Med 1995; 332:494-9; PMID:7830730; http://dx.doi.org/10.1056/NEJM199502233320803
67. J.Krutzfeldt, N.Rajewsky, R.Braich, K.G.Rajeev, T.Tuschl, M.Manoharan, M.Stoffel. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005; 438:685-9; PMID:16258535; http://dx.doi.org/10.1038/nature04303
68. C.Wahlquist, D.Jeong, A.Rojas-Munoz, C.Kho, A.Lee, S.Mitsuyama, A.van Mil, W.J.Park, J.P.Sluijter, P.A.Doevendans, et al. Inhibition of Mir25 improves cardiac contractility in the failing heart. Nature 2014; 508:531-5; PMID:24670661; http://dx.doi.org/10.1038/nature13073
69. A.E.Lovett-Racke, A.E.Rocchini, J.Choy, S.C.Northrop, R.Z.Hussain, R.B.Ratts, D.Sikder, M.K.Racke. Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity 2004; 21:719-31; PMID:15539157; http://dx.doi.org/10.1016/j.immuni.2004.09.010
70. E.Cormet-Boyaka, M.Jablonsky, A.P.Naren, P.L.Jackson, D.D.Muccio, K.L.Kirk. Rescuing cystic fibrosis transmembrane conductance regulator (CFTR)-processing mutants by transcomplementation. Proc Natl Acad Sci U S A 2004; 101:8221-6; PMID:15141088; http://dx.doi.org/10.1073/pnas.0400459101