Identification of a set of miRNAs differentially expressed in transiently TIA-depleted HeLa cells by genome-wide profiling

BMC Molecular Biology

José M Izquierdo²  Juan Barrero¹  Isabel Carrascoso²  Carmen Sánchez-Jiménez² 

[1] Current address: Programa de Biología de Sistemas, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, C/Darwin 3, Cantoblanco, Madrid, 28049, Spain;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

关键词: Gene regulatory networks;    miRNAs;    TIAR;    TIA1;   

Others  :  1091240
DOI  :  10.1186/1471-2199-14-4

 received in 2012-06-26, accepted in 2013-02-04,  发布年份 2013

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2013 Sánchez Jiménez et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]McAlinden A, Liang L, Mukudai Y, Imamura T, Sandell LJ: Nuclear protein TIA1 regulates COL2A1 alternative splicing and interacts with precursor mRNA and genomic DNA. J Biol Chem 2007, 282:24444-24454.
• [2]Suswam EA, Li YY, Mahtani H, King PH: Novel DNA-binding properties of the RNA-binding protein TIAR. Nucleic Acids Res 2005, 33:4507-4518.
• [3]Kim HS, Wilce MC, Yoga YM, Pendini NR, Gunzburg MJ, Cowieson NP, Wilson GM, Williams BR, Gorospe M, Wilce JA: Different modes of interaction by TIAR and HuR with target RNA and DNA. Nucleic Acids Res 2011, 39:1117-1130.
• [4]Das R, Yu J, Zhang Z, Gygi MP, Krainer AR, Gygi SP, Reed R: SR proteins function in coupling RNAP II transcription to pre-mRNA splicing. Mol Cell 2007, 26:867-881.
• [5]Del Gatto-Konczak F, Bourgeois CF, Le Guiner C, Kister L, Gesnel MC, Stevenin J, Breathnach R: The RNA-binding protein TIA1 is a novel mammalian splicing regulator acting through intron sequences adjacent to a 5 splice site. Mol Cell Biol 2000, 20:6287-6299.
• [6]Förch P, Puig O, Kedersha N, Martínez C, Granneman S, Séraphin B, Anderson P, Valcárcel J: The apoptosis-promoting factor TIA1 is a regulator of alternative pre-mRNA splicing. Mol Cell 2000, 6:1089-1098.
• [7]Izquierdo JM, Majós N, Bonnal S, Martínez C, Castelo R, Guigó R, Bilbao D, Valcárcel J: Regulation of Fas alternative splicing by antagonistic effects of TIA1 and PTB on exon definition. Mol Cell 2005, 19:475-484.
• [8]Wang Z, Kayikci M, Briese M, Zarnack K, Luscombe NM, Rot G, Zupan B, Curk T, Ule J: iCLIP predicts the dual splicing effects of TIA-RNA interactions. PLoS Biol 2010, 8:e1000530.
• [9]Yamasaki S, Stoecklin G, Kedersha N, Simarro M, Anderson P: T-cell intracellular antigen-1 (TIA1)-induced translational silencing promotes the decay of selected mRNAs. J Biol Chem 2007, 282:30070-30077.
• [10]Reyes R, Alcalde J, Izquierdo JM: Depletion of T-cell intracellular antigen (TIA)-proteins promotes cell proliferation. Genome Biol 2009, 10:R87.
• [11]López De Silanes I, Galbán S, Martindale JL, Yang X, Mazan-Mamczarz K, Indig FE, Falco G, Zhan M, Gorospe M: Identification and functional outcome of mRNAs associated with RNA-binding protein TIA1. Mol Cell Biol 2005, 25:9520-9531.
• [12]Mazan-Mamczarz K, Lal A, Martindale JL, Kawai T, Gorospe M: Translational repression by RNA-binding protein TIAR. Mol Cell Biol 2006, 26:2716-2727.
• [13]Kim HS, Kuwano Y, Zhan M, Pullmann R Jr, Mazan-Mamczarz K, Li H, Kedersha N, Anderson P, Wilce MC, Gorospe M, Wilce JA: Elucidation of a C-rich signature motif in target mRNAs of RNA-binding protein TIAR. Mol Cell Biol 2007, 27:6806-6817.
• [14]Liao B, Hu Y, Brewer G: Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. Nat Struct Mol Biol 2007, 14:511-518.
• [15]Damgaard CK, Lykke-Andersen J: Translational coregulation of 5′TOP mRNAs by TIA-1 and TIAR. Genes Dev 2011, 25:2057-2068.
• [16]Piecyk M, Wax S, Beck AR, Kedersha N, Gupta M, Maritim B, Chen S, Gueydan C, Kruys V, Streuli M, Anderson P: TIA1 is a translational silencer that selectively regulates the expression of TNF-alpha. EMBO J 2000, 19:4154-4163.
• [17]Beck AR, Miller JJ, Anderson P, Streuli M: RNA-binding protein TIAR is essential for primordial germ cell development. Proc Natl Acad Sci 1998, 95:2331-2336.
• [18]Kharraz Y, Salmand PA, Camus A, Auriol J, Gueydan C, Kruys V, Morello D: Impaired embryonic development in mice overexpressing the RNA-binding protein TIAR. PLoS One 2010, 5:e11352.
• [19]Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009, 136:215-233.
• [20]Smyth GK, Speed TP: Normalization of cDNA microarray data. Methods 2003, 31:265-273.
• [21]Bolstad BM, Irizarry RA, Astrand M, Speed TP: A comparison of normalization methods for high density oligonucleotide array data based on bias and variance. Bioinformatics 2003, 19:185-193.
• [22]Smyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. In statistical applications in genetics and molecular biology 2004. Volume 3. Number 1. Article 3. http://www.bepress.com/sagmb/vol3/iss1/art3 webcite
• [23]Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 1995, 57:289.
• [24]Oliveros JC: FIESTA at BioinfoGP. An interactive server for analyzing DNA microarray experiments with replicates. http://bioinfogp.cnb.csic.es/tools/FIESTA webcite
• [25]Lewis BP, Burge CB, Bartel DP: Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets. Cell 2005, 120:15-20.
• [26]Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N: Combinatorial microRNA target predictions. Nat Genet 2005, 37:495-500.
• [27]Wang X, El Naqa IM: Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 2008, 24:325-332.
• [28]Wang X: miRDB: a microRNA target prediction and functional annotation database with a wiki interface. RNA 2008, 14:1012-1017.
• [29]Kozomara A, Griffiths-Jones S: miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011, 39:D152-D157.
• [30]Carmona-Saez P, Chagoyen M, Tirado F, Carazo JM, Pascual-Montano A: GENECODIS: a web-based tool for finding significant concurrent annotations in gene lists. Genome Biol 2007, 8:R3.
• [31]Nogales-Cadenas R, Carmona-Saez P, Vazquez M, Vicente C, Yang X, Tirado F, Carazo JM, Pascual-Montano A: GeneCoDis: interpreting gene lists through enrichment analysis and integration of diverse biological information. Nucleic Acids Res 2009, 37:W317-W322.
• [32]Smoot M, Ono K, Ruscheinski J, Wang P-L, Ideker T: Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011, 27:431-432.
• [33]Friedman RC, Farh KK, Burge CB, Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009, 19:92-105.
• [34]Guo H, Ingolia NT, Weissman JS, Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010, 466:835-840.
• [35]Ebert MS, Sharp PA: Roles for microRNAs in conferring robustness to biological processes. Cell 2012, 149:515-524.
• [36]Krol J, Loedige I, Fillipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010, 11:597-610.
• [37]Huang V, Place RF, Portnoy V, Wang J, Qi Z, Jia Z, Yu A, Shuman M, Yu J, Li LC: Upregulation of Cyclin B1 by miRNA and its implications in cancer. Nucleic Acids Res 2012, 40:1695-1707.
• [38]Iliopoulos D, Hirsch HA, Struhl K: An epigenetic switch involving NF-kappaB, Lin28, Let-3 MicroRNA, and IL6 links inflammation to cell transformation. Cell 2009, 139:693-706.
• [39]Mangan S, Alon U: Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci USA 2003, 10:11980-11985.
• [40]Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R, Boshoff C: The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood 2012. in press
• [41]Quintavalle C, Donnarumma E, Iaboni M, Roscigno G, Garofalo M, Romano G, Fiore D, De Marinis P, Croce CM, Condorelli G: Effect of miR-21 and miR-30b/c on TRAIL-induced apoptosis in glioma cells. Oncogene 2012.
• [42]Shao C, Yu Y, Yu L, Pei Y, Feng Q, Chu F, Fang Z, Zhou Y: Amplification and up-regulation of microRNA-30b in oral squamous cell cancers. Arch Oral Biol 2012, 57:1012-1017.
• [43]Yang Y, Zhou L, Lu L, Wang L, Li X, Jiang P, Chan LK, Zhang T, Yu J, Kwong J, Cheung TH, Chung T, Mak K, Sun H, Wang H: A novel miR-193a-5p-YY1-APC regulatory axis in human endometrioid endometrial adenocarcinoma. Oncogene 2012. Aug 20
• [44]Moes M, Le Béchec A, Crespo I, Laurini C, Halavatyi A, Vetter G, Del Sol A, Friederich E: A novel network integrating a miRNA-203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition. PLoS One 2012, 7:e35440.
• [45]Moffatt CE, Lamont RJ: Porphyromonas gingivalis induction of microRNA-203 expression controls suppressor of cytokine signaling 3 in gingival epithelial cells. Infect Immun 2011, 79:2632-2637.
• [46]Kelly TJ, Souza AL, Clish CB, Puigserver P: A hypoxia-induced positive feedback loop promotes hypoxia-inducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like. Mol Cell Biol 2011, 31:2696-2706.
• [47]Noman MZ, Buart S, Romero P, Ketari S, Janji B, Mari B, Mami-Chouaib F, Chouaib S: Hypoxia-inducible miR-210 regulates the susceptibility of tumor cells to lysis by cytotoxic T cells. Cancer Res 2012, 72:4629-4641.
• [48]Yoshioka Y, Kosaka N, Ochiya T, Kato T: Micromanaging iron homeostasis: hypoxia-inducible miR-210 suppresses iron homeostasis-related proteins. J Biol Chem 2012, 287:34110-34119.
• [49]Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, Vojnovic B, Pires Das Neves R, Glazer P, Iborra F, Ivan M, Ragoussis J, Harris AL: MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS One 2010, 26:e10345.
• [50]Chen Z, Li Y, Zhang H, Huang P, Luthra R: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 2010, 29:4362-4368.
• [51]Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G: MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem 2011, 286:420-428.
• [52]Gou D, Ramchandran R, Peng X, Yao L, Kang K, Sarkar J, Wang Z, Zhou G, Raj JU: miR-210 has an anti-apoptotic effect in pulmonary artery smooth muscle cells during hypoxia. Am J Physiol Lung Cell Mol Physiolin press
• [53]Hong L, Yang J, Han Y, Lu Q, Cao J, Syed L: High expression of miR-210 predicts poor survival in patients with breast cancer: a meta-analysis. Gene 2012, 507:135-138.
• [54]Lou YL, Guo F, Liu F, Gao FL, Zhang PQ, Niu X, Guo SC, Yin JH, Wang Y, Deng ZF: miR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia. Mol Cell Biochemin press
• [55]Liu P, Wilson MJ: miR-520c and miR-373 upregulate MMP9 expression by targeting mTOR and SIRT1, and activate the Ras/Raf/MEK/Erk signaling pathway and NF-κB factor in human fibrosarcoma cells. J Cell Physiol 2012, 227:867-876.
• [56]Wu N, Liu X, Xu X, Fan X, Liu M, Li X, Zhong Q, Tang H: MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma. FEBS J 2011, 278:2044-2054.
• [57]Lee KH, Goan YG, Hsiao M, Lee CH, Jian SH, Lin JT, Chen YL, Lu PJ: MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer. Exp Cell Res 2009, 315:2529-2538.
• [58]Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, Liu YP, van Duijse J, Drost J, Griekspoor A, Zlotorynski E, Yabuta N, De Vita G, Nojima H, Looijenga LH, Agami R: A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 2006, 124:1169-1181.
• [59]Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ, Gimotty PA, Katsaros D, Coukos G, Zhang L, Puré E, Agami R: The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 2008, 10:202-210.
• [60]Crosby ME, Kulshreshtha R, Ivan M, Glazer PM: MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res 2009, 69:1221-1229.
• [61]von Frowein J, Pagel P, Kappler R, von Schweinitz D, Roscher A, Schmid I: MicroRNA-492 is processed from the keratin 19 gene and up-regulated in metastatic hepatoblastoma. Hepatology 2011, 53:833-842.
• [62]Gaedcke J, Grade M, Camps J, Søkilde R, Kaczkowski B, Schetter AJ, Difilippantonio MJ, Harris CC, Ghadimi BM, Møller S, Beissbarth T, Ried T, Litman T: The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa. Clin Cancer Res 2012, 18:4919-4930.
• [63]Schultz NA, Werner J, Willenbrock H, Roslind A, Giese N, Horn T, Wøjdemann M, Johansen JS: MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma. Mod Patholin press
• [64]Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjøt L, Wiuf C, Sørensen FJ, Kruhøffer M, Laurberg S, Kauppinen S, Ørntoft TF, Andersen CL: Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res 2008, 68:6416-6424.
• [65]Caporali A, Meloni M, Völlenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, Agami R, le Sage C, Condorelli G, Madeddu P, Martelli F, Emanueli C: Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation 2011, 123:282-291.
• [66]Zhou J, Wang W: Analysis of microRNA expression profiling identifies microRNA-503 regulates metastatic function in hepatocellular cancer cell. J Surg Oncol 2011, 104:278-283.
• [67]Cui YH, Xiao L, Rao JN, Zou T, Liu L, Chen Y, Turner DJ, Gorospe M, Wang JY: miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies. Mol Biol Cell 2012, 23:151-162.
• [68]Caporali A, Emanueli C: MicroRNA-503 and the extended microRNA-16 family in angiogenesis. Trends Cardiovasc Med 2011, 21:162-166.
• [69]Zhu DX, Zhu W, Fang C, Fan L, Zou ZJ, Wang YH, Liu P, Hong M, Miao KR, Liu P, Xu W, Li JY: miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis genes. Carcinogenesis 2012, 33:1294-1301.
• [70]Xiao W, Bao ZX, Zhang CY, Zhang XY, Shi LJ, Zhou ZT, Jiang WW: Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia. PLoS One 2012, 7:e38648.
• [71]Cummins JM, He Y, Leary RJ, Pagliarini R, Diaz LA Jr, Sjoblom T, Barad O, Bentwich Z, Szafranska AE, Labourier E, Raymond CK, Roberts BS, Juhl H, Kinzler KW, Vogelstein B, Velculescu VE: The colorectal microRNAome. Proc Natl Acad Sci 2006, 103:3687-3692.
• [72]Guled M, Lahti L, Lindholm PM, Salmenkivi K, Bagwan I, Nicholson AG, Knuutila S: CDKN2A, NF2, And JUN are dysregulated among other genes by miRNAs in malignant mesothelioma. A miRNA microarray analysis. Genes Chromosomes Cancer 2009, 48:615-623.
• [73]Jiang A, Zhang S, Li Z, Liang R, Ren S, Li J, Pu Y, Yang J: miR-615-3p promotes the phagocytic capacity of splenic macrophages by targeting ligand-dependent nuclear receptor corepressor in cirrhosis-related portal hypertension. Exp Biol Med 2011, 236:672-680.
• [74]Wang M, Li C, Nie H, Lv X, Qu Y, Yu B, Su L, Li J, Chen X, Ju J, Yu Y, Yan M, Gu Q, Zhu Z, Liu B: Down-regulated miR-625 suppresses invasion and metastasis of gastric cancer by targeting ILK. FEBS Lett 2012, 586:2382-2388.
• [75]Yang L, Li Y, Cheng M, Huang D, Zheng J, Liu B, Ling X, Li Q, Zhang X, Ji W, Zhou Y, Lu J: A functional polymorphism at microRNA-629-binding site in the 3′-untranslated region of NBS1 gene confers an increased risk of lung cancer in Southern and Eastern Chinese population. Carcinogenesis 2012, 33:338-347.
• [76]Li D, Wang Q, Liu C, Duan H, Zeng X, Zhang B, Li X, Zhao J, Tang S, Li Z, Xing X, Yang P, Chen L, Zeng J, Zhu X, Zhang S, Zhang Z, Ma L, He Z, Wang E, Xiao Y, Zheng Y, Chen W: Aberrant expression of miR-638 contributes to benzo(a)pyrene-induced human cell transformation. Toxicol Sci 2012, 125:382-391.
• [77]Guo J, Miao Y, Xiao B, Huan R, Jiang Z, Meng D, Wang Y: Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol 2009, 24:652-657.
• [78]Liu ZY, Zhang GL, Wang MM, Xiong YN, Cui HQ: MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation. Asian Pac J Cancer Prev 2011, 12:2819-2823.
• [79]Tili E, Michaille JJ, Adair B, Alder H, Limagne E, Taccioli C, Ferracin M, Delmas D, Latruffe N, Croce CM: Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis 2010, 31:1561-1566.
• [80]Yi C, Wang Q, Wang L, Huang Y, Li L, Liu L, Zhou X, Xie G, Kang T, Wang H, Zeng M, Ma J, Zeng Y, Yun JP: MiR-663, a microRNA targeting p21(WAF1/CIP1), promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma. Oncogene 2012, 1:1-13.
• [81]Ni CW, Qiu H, Jo H: MicroRNA-663 upregulated by oscillatory shear stress plays a role in inflammatory response of endothelial cells. Am J Physiol Heart Circ Physiol 2011, 300:H1762-H1769.
• [82]Rutnam ZJ, Yang BB: The non-coding 3′ UTR of CD44 induces metastasis by regulating extracellular matrix functions. J Cell Sci 2012, 125:2075-2085.
• [83]Hansen TB, Wiklund ED, Bramsen JB, Villadsen SB, Statham AL, Clark SJ, Kjems J: miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J 2011, 30:4414-4422.
• [84]Martin J, Jenkins RH, Bennagi R, Krupa A, Phillips AO, Bowen T, Fraser DJ: Post-transcriptional regulation of transforming growth factor beta-1 by microRNA-744. PLoS One 2011, 6:e25044.
• [85]Wang L, Shi M, Hou S, Ding B, Liu L, Ji X, Zhang J, Deng Y: MiR-483-5p suppresses the proliferation of glioma cells via directly targeting ERK1. FEBS Lett 2012, 586:1312-1317.
• [86]Qiao Y, Ma N, Wang X, Hui Y, Li F, Xiang Y, Zhou J, Zou C, Jin J, Lv G, Jin H, Gao X: MiR-483-5p controls angiogenesis in vitro and targets serum response factor. FEBS Lett 2011, 585:3095-3100.
• [87]Soon PS, Tacon LJ, Gill AJ, Bambach CP, Sywak MS, Campbell PR, Yeh MW, Wong SG, Clifton-Bligh RJ, Robinson BG, Sidhu SB: miR-195 and miR-483-5p identified as predictors of poor prognosis in adrenocortical cancer. Clin Cancer Res 2009, 15:7684-7692.
• [88]Jiang L, Huang Q, Zhang S, Zhang Q, Chang J, Qiu X, Wang E: Hsa-miR-125a-3p and hsa-miR-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells. BMC Cancer 2010, 10:318.
• [89]Hashiguchi Y, Nishida N, Mimori K, Sudo T, Tanaka F, Shibata K, Ishii H, Mochizuki H, Hase K, Doki Y, Mori M: Down-regulation of miR-125a-3p in human gastric cancer and its clinicopathological significance. Int J Oncol 2012, 40:1477-1482.
• [90]Friard O, Re A, Taverna D, De Bortoli M, Corá D, Circuits DB: a database of mixed microRNA/transcription factor feed-forward regulatory circuits in human and mouse. BMC Bioinforma 2010, 11:435.