title: Identification of a set of miRNAs differentially expressed in transiently TIA-depleted HeLa cells by genome-wide profiling.
abstract: BACKGROUND
  T-cell intracellular antigen (TIA) proteins function as regulators of cell homeostasis. These proteins control gene expression globally at multiple levels in response to dynamic regulatory changes and environmental stresses. Herein we identified a micro(mi)RNA signature associated to transiently TIA-depleted HeLa cells and analyzed the potential role of miRNAs combining genome-wide analysis data on mRNA and miRNA profiles.
  
  
  RESULTS
  Using high-throughput miRNA expression profiling, transient depletion of TIA-proteins in HeLa cells was observed to promote significant and reproducible changes affecting to a pool of up-regulated miRNAs involving miR-30b-3p, miR125a-3p, miR-193a-5p, miR-197-3p, miR-203a, miR-210, miR-371-5p, miR-373-5p, miR-483-5p, miR-492, miR-498, miR-503-5p, miR-572, miR-586, miR-612, miR-615-3p, miR-623, miR-625-5p, miR-629-5p, miR-638, miR-658, miR-663a, miR-671-5p, miR-769-3p and miR-744-5p. Some up-regulated and unchanged miRNAs were validated and previous results confirmed by reverse transcription and real time PCR. By target prediction of the miRNAs and combined analysis of the genome-wide expression profiles identified in TIA-depleted HeLa cells, we detected connections between up-regulated miRNAs and potential target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis suggest that target genes are related with biological processes associated to the regulation of DNA-dependent transcription, signal transduction and multicellular organismal development as well as with the enrichment of pathways involved in cancer, focal adhesion, regulation of actin cytoskeleton, endocytosis and MAPK and Wnt signaling pathways, respectively. When the collection of experimentally defined differentially expressed genes in TIA-depleted HeLa cells was intersected with potential target genes only 7 out of 68 (10%) up- and 71 out of 328 (22%) down-regulated genes were shared. GO and KEGG database analyses showed that the enrichment categories of biological processes and cellular pathways were related with innate immune response, signal transduction, response to interleukin-1, glomerular basement membrane development as well as neuroactive ligand-receptor interaction, endocytosis, lysosomes and apoptosis, respectively.
  
  
  CONCLUSIONS
  All this considered, these observations suggest that individual miRNAs could act as potential mediators of the epigenetic switch linking transcriptomic dynamics and cell phenotypes mediated by TIA proteins.
authors: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid (CSIC/UAM), C/Nicolás Cabrera 1, Cantoblanco, Madrid 28049, Spain.
authors: Carmen
authors: C
authors: Sánchez-Jiménez
authors: Isabel
authors: I
authors: Carrascoso
authors: Juan
authors: J
authors: Barrero
authors: José M
authors: JM
authors: Izquierdo
mesh_terms: D020869:Gene Expression Profiling; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D039102:Poly(A)-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D035683:MicroRNAs; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human
references: Cell. 2009 Nov 13;139(4):693-706
references: 19878981
references: Nat Genet. 2005 May;37(5):495-500
references: 15806104
references: Mol Cell Biol. 2011 Jul;31(13):2696-706
references: 21555452
references: Mod Pathol. 2012 Dec;25(12):1609-22
references: 22878649
references: Bioinformatics. 2011 Feb 1;27(3):431-2
references: 21149340
references: Infect Immun. 2011 Jul;79(7):2632-7
references: 21536793
references: Mol Cell Biochem. 2012 Nov;370(1-2):45-51
references: 22833359
references: Carcinogenesis. 2012 Feb;33(2):338-47
references: 22114071
references: Cancer Res. 2012 Sep 15;72(18):4629-41
references: 22962263
references: Mol Cell. 2005 Aug 19;19(4):475-84
references: 16109372
references: Nucleic Acids Res. 2011 Feb;39(3):1117-30
references: 21233170
references: Cell. 2006 Mar 24;124(6):1169-81
references: 16564011
references: J Cell Physiol. 2012 Feb;227(2):867-76
references: 21898400
references: Genome Res. 2009 Jan;19(1):92-105
references: 18955434
references: Trends Cardiovasc Med. 2011 Aug;21(6):162-6
references: 22814423
references: J Biol Chem. 2007 Oct 12;282(41):30070-7
references: 17711853
references: Mol Cell. 2000 Nov;6(5):1089-98
references: 11106748
references: J Gastroenterol Hepatol. 2009 Apr;24(4):652-7
references: 19175831
references: J Biol Chem. 2007 Aug 17;282(33):24444-54
references: 17580305
references: Gene. 2012 Oct 10;507(2):135-8
references: 22842193
references: Circulation. 2011 Jan 25;123(3):282-91
references: 21220732
references: BMC Cancer. 2010 Jun 22;10:318
references: 20569443
references: Oncogene. 2013 Aug 22;32(34):4001-8
references: 22964638
references: Genes Dev. 2011 Oct 1;25(19):2057-68
references: 21979918
references: Arch Oral Biol. 2012 Aug;57(8):1012-7
references: 22542163
references: BMC Bioinformatics. 2010 Aug 23;11:435
references: 20731828
references: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2331-6
references: 9482885
references: Nature. 2010 Aug 12;466(7308):835-40
references: 20703300
references: Oncogene. 2012 Oct 11;31(41):4421-33
references: 22249270
references: Bioinformatics. 2008 Feb 1;24(3):325-32
references: 18048393
references: Mol Cell Biol. 2006 Apr;26(7):2716-27
references: 16537914
references: Clin Cancer Res. 2012 Sep 15;18(18):4919-30
references: 22850566
references: Int J Oncol. 2012 May;40(5):1477-82
references: 22322911
references: Oncogene. 2010 Jul 29;29(30):4362-8
references: 20498629
references: Nucleic Acids Res. 2012 Feb;40(4):1695-707
references: 22053081
references: Genome Biol. 2007;8(1):R3
references: 17204154
references: PLoS One. 2012;7(4):e35440
references: 22514743
references: Cell. 2012 Apr 27;149(3):515-24
references: 22541426
references: Mol Cell Biol. 2000 Sep;20(17):6287-99
references: 10938105
references: PLoS One. 2010 Jun 28;5(6):e11352
references: 20596534
references: Toxicol Sci. 2012 Feb;125(2):382-91
references: 22048643
references: Clin Cancer Res. 2009 Dec 15;15(24):7684-7692
references: 19996210
references: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):11980-5
references: 14530388
references: Nat Struct Mol Biol. 2007 Jun;14(6):511-8
references: 17486099
references: PLoS One. 2011;6(10):e25044
references: 21991303
references: PLoS Biol. 2010 Oct 26;8(10):e1000530
references: 21048981
references: Nat Rev Genet. 2010 Sep;11(9):597-610
references: 20661255
references: Mol Cell Biol. 2005 Nov;25(21):9520-31
references: 16227602
references: PLoS One. 2010 Apr 26;5(4):e10345
references: 20436681
references: Mol Biol Cell. 2012 Jan;23(1):151-62
references: 22072795
references: FEBS J. 2011 Jun;278(12):2044-54
references: 21481188
references: J Biol Chem. 2012 Oct 5;287(41):34110-9
references: 22896707
references: Genes Chromosomes Cancer. 2009 Jul;48(7):615-23
references: 19396864
references: Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3687-92
references: 16505370
references: J Cell Sci. 2012 Apr 15;125(Pt 8):2075-85
references: 22637644
references: Nucleic Acids Res. 2005 Aug 09;33(14):4507-18
references: 16091628
references: Cancer Res. 2009 Feb 1;69(3):1221-9
references: 19141645
references: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W317-22
references: 19465387
references: EMBO J. 2000 Aug 1;19(15):4154-63
references: 10921895
references: Oncogene. 2013 Jul 18;32(29):3432-42
references: 22907428
references: Cell. 2009 Jan 23;136(2):215-33
references: 19167326
references: RNA. 2008 Jun;14(6):1012-7
references: 18426918
references: EMBO J. 2011 Sep 30;30(21):4414-22
references: 21964070
references: Am J Physiol Lung Cell Mol Physiol. 2012 Oct 15;303(8):L682-91
references: 22886504
references: Cell. 2005 Jan 14;120(1):15-20
references: 15652477
references: Asian Pac J Cancer Prev. 2011;12(11):2819-23
references: 22393947
references: FEBS Lett. 2012 May 7;586(9):1312-7
references: 22465663
references: Blood. 2012 Dec 13;120(25):5063-72
references: 23086751
references: Cancer Res. 2008 Aug 1;68(15):6416-24
references: 18676867
references: Nat Cell Biol. 2008 Feb;10(2):202-10
references: 18193036
references: Mol Cell Biol. 2007 Oct;27(19):6806-17
references: 17682065
references: Exp Biol Med (Maywood). 2011 Jun 1;236(6):672-80
references: 21565892
references: Carcinogenesis. 2010 Sep;31(9):1561-6
references: 20622002
references: PLoS One. 2012;7(6):e38648
references: 22719913
references: Mol Cell. 2007 Jun 22;26(6):867-81
references: 17588520
references: Hepatology. 2011 Mar;53(3):833-42
references: 21319197
references: J Biol Chem. 2011 Jan 7;286(1):420-8
references: 21044961
references: FEBS Lett. 2011 Oct 3;585(19):3095-100
references: 21893058
references: Stat Appl Genet Mol Biol. 2004;3:Article3
references: 16646809
references: Bioinformatics. 2003 Jan 22;19(2):185-93
references: 12538238
references: Am J Physiol Heart Circ Physiol. 2011 May;300(5):H1762-9
references: 21378144
references: FEBS Lett. 2012 Jul 30;586(16):2382-8
references: 22677169
references: J Surg Oncol. 2011 Sep 1;104(3):278-83
references: 21495032
references: Genome Biol. 2009;10(8):R87
references: 19709424
references: Carcinogenesis. 2012 Jul;33(7):1294-301
references: 22610076
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D152-7
references: 21037258
references: Exp Cell Res. 2009 Sep 10;315(15):2529-38
references: 19501585
references: Methods. 2003 Dec;31(4):265-73
references: 14597310