Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB
Abstract
MicroRNAs regulate pathways contributing to oncogenesis, and thus the mechanisms causing dysregulation of microRNA expression in cancer are of significant interest. Mature mir‐29b levels are decreased in malignant cells, and this alteration promotes the malignant phenotype, including apoptosis resistance. However, the mechanism responsible for mir‐29b suppression is unknown. Here, we examined mir‐29 expression from chromosome 7q32 using cholangiocarcinoma cells as a model for mir‐29b downregulation. Using 5′ rapid amplification of cDNA ends, the transcriptional start site was identified for this microRNA locus. Computational analysis revealed the presence of two putative E‐box (Myc‐binding) sites, a Gli‐binding site, and four NF‐κB‐binding sites in the region flanking the transcriptional start site. Promoter activity in cholangiocarcinoma cells was repressed by transfection with c‐Myc, consistent with reports in other cell types. Treatment with the hedgehog inhibitor cyclopamine, which blocks smoothened signaling, increased the activity of the promoter and expression of mature mir‐29b. Mutagenesis analysis and gel shift data are consistent with a direct binding of Gli to the mir‐29 promoter. Finally, activation of NF‐κB signaling, via ligation of Toll‐like receptors, also repressed mir‐29b expression and promoter function. Of note, activation of hedgehog, Toll‐like receptor, and c‐Myc signaling protected cholangiocytes from TRAIL‐induced apoptosis. Thus, in addition to c‐Myc, mir‐29 expression can be suppressed by hedgehog signaling and inflammatory pathways, both commonly activated in the genesis of human malignancies. J. Cell. Biochem. 110: 1155–1164, 2010. Published 2010 Wiley‐Liss, Inc.
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miR-29a and miR-29b-1, like miR-29b-2 and miR-29c, are apparently co-transcribed as polycistronic primary transcripts.
“This is interesting because miR-29a and miR-29b-1, like miR-29b-2 and miR-29c, are apparently co-transcribed as polycistronic primary transcripts [15].”
From Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells (2014) · cites this paper as [15]
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Cites
Nuclear factor-κB in cancer development and progression
Karin, M. (2006) · Nature · doi:10.1038/nature04870 · Cited by 3,519 · see citing works
Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis
Chang, T.-C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C. J., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.010 · Cited by 2,010 · see citing works
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Research works printed but not linked: 47
- Berman DM Karhadkar SS Maitra A Montes De Oca R Gerstenblith MR Briggs K Parker AR Shimada Y Eshleman JR Watkins DN Beachy PA 2003 Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours Nature 425 846 51 14520411
- Bigelow RL Chari NS Unden AB Spurgers KB Lee S Roop DR Toftgard R McDonnell TJ 2004 Transcriptional regulation of bcl-2 mediated by the sonic hedgehog signaling pathway through gli-1 J Biol Chem 279 1197 205 14555646
- Black DL 2003 Mechanisms of alternative pre-messenger RNA splicing Annu Rev Biochem 72 291 336 12626338
- Chang TC Yu D Lee YS Wentzel EA Arking DE West KM Dang CV Thomas-Tikhonenko A Mendell JT 2008 Widespread microRNA repression by Myc contributes to tumorigenesis Nat Genet 40 43 50 18066065 PMC2628762
- Chen XM O’Hara SP Nelson JB Splinter PL Small AJ Tietz PS Limper AH LaRusso NF 2005 Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-kappaB J Immunol 175 7447 56 16301652
- D’Agnano I Valentini A Fornari C Bucci B Starace G Felsani A Citro G 2001 Myc down-regulation induces apoptosis in M14 melanoma cells by increasing p27(kip1) levels Oncogene 20 2814 25 11420693
- Davis BN Hilyard AC Lagna G Hata A 2008 SMAD proteins control DROSHA-mediated microRNA maturation Nature 454 56 61 18548003 PMC2653422
- Evan GI Wyllie AH Gilbert CS Littlewood TD Land H Brooks M Waters CM Penn LZ Hancock DC 1992 Induction of apoptosis in fibroblasts by c-myc protein Cell 69 119 28 1555236
- Fabbri M Garzon R Cimmino A Liu Z Zanesi N Callegari E Liu S Alder H Costinean S Fernandez-Cymering C Volinia S Guler G Morrison CD Chan KK Marcucci G Calin GA Huebner K Croce CM 2007 MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B Proc Natl Acad Sci U S A 104 15805 10 17890317 PMC2000384
- Flynt AS Li N Thatcher EJ Solnica-Krezel L Patton JG 2007 Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate Nat Genet 39 259 63 17220889 PMC3982799
- Garzon R Heaphy CE Havelange V Fabbri M Volinia S Tsao T Zanesi N Kornblau SM Marcucci G Calin GA Andreeff M Croce CM 2009a MicroRNA 29b functions in acute myeloid leukemia Blood PMC2796138 19850741
- Gatti G Maresca G Natoli M Florenzano F Nicolin A Felsani A D’Agnano I 2009 MYC prevents apoptosis and enhances endoreduplication induced by paclitaxel PLoS One 4 e5442 19421315 PMC2673584
- Gebeshuber CA Zatloukal K Martinez J 2009 miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis EMBO Rep 10 400 5 19247375 PMC2672883
- Grossmann M O’Reilly LA Gugasyan R Strasser A Adams JM Gerondakis S 2000 The anti-apoptotic activities of Rel and RelA required during B-cell maturation involve the regulation of Bcl-2 expression Embo J 19 6351 60 11101508 PMC305873
- Grubman SA Perrone RD Lee DW Murray SL Rogers LC Wolkoff LI Mulberg AE Cherington V Jefferson DM 1994 Regulation of intracellular pH by immortalized human intrahepatic biliary epithelial cell lines Am J Physiol 266 G1060 70 8023938
- Harada K Ohira S Isse K Ozaki S Zen Y Sato Y Nakanuma Y 2003 Lipopolysaccharide activates nuclear factor-kappaB through toll-like receptors and related molecules in cultured biliary epithelial cells Lab Invest 83 1657 67 14615419
- Jiang J Hui CC 2008 Hedgehog signaling in development and cancer Dev Cell 15 801 12 19081070 PMC6443374
- Kasper M Regl G Frischauf AM Aberger F 2006 GLI transcription factors: mediators of oncogenic Hedgehog signalling Eur J Cancer 42 437 45 16406505
- Kim YK Kim VN 2007 Processing of intronic microRNAs Embo J 26 775 83 17255951 PMC1794378
- Kobayashi S Werneburg NW Bronk SF Kaufmann SH Gores GJ 2005 Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt-signaling pathway in cholangiocarcinoma cells Gastroenterology 128 2054 65 15940637
- Kucharczak J Simmons MJ Fan Y Gelinas C 2003 To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis Oncogene 22 8961 82 14663476
- Kump E Ji J Wernli M Hausermann P Erb P 2008 Gli2 upregulates cFlip and renders basal cell carcinoma cells resistant to death ligand-mediated apoptosis Oncogene 27 3856 64 18264131
- Lee EJ Baek M Gusev Y Brackett DJ Nuovo GJ Schmittgen TD 2008 Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors Rna 14 35 42 18025253 PMC2151027
- Lee HH Dadgostar H Cheng Q Shu J Cheng G 1999 NF-kappaB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes Proc Natl Acad Sci U S A 96 9136 41 10430908 PMC17745
- Lee Y Ahn C Han J Choi H Kim J Yim J Lee J Provost P Radmark O Kim S Kim VN 2003 The nuclear RNase III Drosha initiates microRNA processing Nature 425 415 9 14508493
- Mott JL Kobayashi S Bronk SF Gores GJ 2007 mir-29 regulates Mcl-1 protein expression and apoptosis Oncogene 26 6133 40 17404574 PMC2432524
- Northcott PA Fernandez LA Hagan JP Ellison DW Grajkowska W Gillespie Y Grundy R Van Meter T Rutka JT Croce CM Kenney AM Taylor MD 2009 The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors Cancer Res 69 3249 55 19351822 PMC2836891
- O’Donnell KA Wentzel EA Zeller KI Dang CV Mendell JT 2005 c-Myc-regulated microRNAs modulate E2F1 expression Nature 435 839 43 15944709
- O’Hara SP Splinter PL Gajdos GB Trussoni CE Fernandez-Zapico ME Chen XM Larusso NF 2009 NF{kappa}B p50-CCAAT-enhancer binding protein beta (C/EBP{beta})-mediated transcriptional repression of microRNA let-7i following microbial infection J Biol Chem PMC2804168 19903813
- Park SY Lee JH Ha M Nam JW Kim VN 2009 miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42 Nat Struct Mol Biol 16 23 9 19079265
- Pekarsky Y Santanam U Cimmino A Palamarchuk A Efanov A Maximov V Volinia S Alder H Liu CG Rassenti L Calin GA Hagan JP Kipps T Croce CM 2006 Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181 Cancer Res 66 11590 3 17178851
- Pikarsky E Porat RM Stein I Abramovitch R Amit S Kasem S Gutkovich-Pyest E Urieli-Shoval S Galun E Ben-Neriah Y 2004 NF-kappaB functions as a tumour promoter in inflammation-associated cancer Nature 431 461 6 15329734
- Porkka KP Pfeiffer MJ Waltering KK Vessella RL Tammela TL Visakorpi T 2007 MicroRNA expression profiling in prostate cancer Cancer Res 67 6130 5 17616669
- Raver-Shapira N Marciano E Meiri E Spector Y Rosenfeld N Moskovits N Bentwich Z Oren M 2007 Transcriptional activation of miR-34a contributes to p53-mediated apoptosis Mol Cell 26 731 43 17540598
- Ricci MS Jin Z Dews M Yu D Thomas-Tikhonenko A Dicker DT El-Deiry WS 2004 Direct repression of FLIP expression by c-myc is a major determinant of TRAIL sensitivity Mol Cell Biol 24 8541 55 15367674 PMC516765
- Ricci MS Kim SH Ogi K Plastaras JP Ling J Wang W Jin Z Liu YY Dicker DT Chiao PJ Flaherty KT Smith CD El-Deiry WS 2007 Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death Cancer Cell 12 66 80 17613437
- Sengupta S den Boon JA Chen IH Newton MA Stanhope SA Cheng YJ Chen CJ Hildesheim A Sugden B Ahlquist P 2008 MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins Proc Natl Acad Sci U S A 105 5874 8 18390668 PMC2311339
- Taniai M Grambihler A Higuchi H Werneburg N Bronk SF Farrugia DJ Kaufmann SH Gores GJ 2004 Mcl-1 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in human cholangiocarcinoma cells Cancer Res 64 3517 24 15150106
- Tarasov V Jung P Verdoodt B Lodygin D Epanchintsev A Menssen A Meister G Hermeking H 2007 Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest Cell Cycle 6 1586 93 17554199
- Tokumoto N Ikeda S Ishizaki Y Kurihara T Ozaki S Iseki M Shimizu Y Itamoto T Arihiro K Okajima M Asahara T 2005 Immunohistochemical and mutational analyses of Wnt signaling components and target genes in intrahepatic cholangiocarcinomas Int J Oncol 27 973 80 16142313
- Tsukahara T Kannagi M Ohashi T Kato H Arai M Nunez G Iwanaga Y Yamamoto N Ohtani K Nakamura M Fujii M 1999 Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax J Virol 73 7981 7 10482545 PMC112812
- Uziel T Karginov FV Xie S Parker JS Wang YD Gajjar A He L Ellison D Gilbertson RJ Hannon G Roussel MF 2009 The miR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma Proc Natl Acad Sci U S A 106 2812 7 19196975 PMC2636735
- Voravud N Foster CS Gilbertson JA Sikora K Waxman J 1989 Oncogene expression in cholangiocarcinoma and in normal hepatic development Hum Pathol 20 1163 8 2574140
- Wang H Garzon R Sun H Ladner KJ Singh R Dahlman J Cheng A Hall BM Qualman SJ Chandler DS Croce CM Guttridge DC 2008 NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma Cancer Cell 14 369 81 18977326 PMC3829205
- Yanaihara N Caplen N Bowman E Seike M Kumamoto K Yi M Stephens RM Okamoto A Yokota J Tanaka T Calin GA Liu CG Croce CM Harris CC 2006 Unique microRNA molecular profiles in lung cancer diagnosis and prognosis Cancer Cell 9 189 98 16530703
- Zhang X Liu S Hu T Liu S He Y Sun S 2009 Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression Hepatology 50 490 9 19472311
- Zong WX Edelstein LC Chen C Bash J Gelinas C 1999 The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalpha-induced apoptosis Genes Dev 13 382 7 10049353 PMC316475
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Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells
Wang, W.-X., Danaher, R. J., Miller, C. S., Berger, J. R., Nubia, V. G., Wilfred, B. S., Neltner, J. H., Norris, C. M., & Nelson, P. T. (2014) · Genomics, Proteomics & Bioinformatics · doi:10.1016/j.gpb.2013.10.003 · Cited by 67 · see citing works
Wang, J., Wang, Y., Wang, Y., Ma, Y., Lan, Y., & Yang, X. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444463 · Cited by 64 · see citing works
- Authors
- Mott, J. L., Kurita, S., Cazanave, S. C., Bronk, S. F., Werneburg, N. W., & Fernandez‐Zapico, M. E.
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2010-07-14
- Volume
- 110
- Issue
- 5
- Pages
- 1155-1164
- ISSN
- 0730-2312
- 1097-4644
- PMC
- PMC2922950
- Cited by
- 233
- References
- 2
- Language
- en
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