Abstract
Signaling pathways are essential intracellular networks that coordinate molecular outcomes to external stimuli. Tight regulation of these pathways is essential to ensure an appropriate response. MicroRNA (miRNA) is a class of small, non-coding RNA that regulates gene expression at a post-transcriptional level by binding to the complementary sequence on target mRNA, thus limiting protein translation. Intracellular pathways are controlled by protein regulators, such as suppressor of cytokine signaling and A20. Until recently, expression of these classical protein regulators was thought to be controlled solely by transcriptional induction and proteasomal degradation; however, there is a growing body of evidence describing their regulation by miRNA. This new information has transformed our understanding of cell signaling by adding a previously unknown layer of regulatory control. This review outlines the miRNA regulation of these classical protein regulators and describes their broad effects at both cellular and disease levels. We review the regulation of three important signaling pathways, including the JAK/STAT, NF-κB, and TGF-β pathways, and summarize an extensive catalog of their regulating miRNAs. This information highlights the importance of the miRNA regulon and reveals a previously unknown regulatory landscape that must be included in the identification and development of novel therapeutic targets for clinical disorders.
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References
Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309:1519–1524
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
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 425:415–419
Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN (2004) The Drosha–DGCR8 complex in primary microRNA processing. Genes Dev 18:3016–3027
Gwizdek C, Ossareh-Nazari B, Brownawell AM, Doglio A, Bertrand E, Macara IG, Dargemont C (2003) Exportin-5 mediates nuclear export of minihelix-containing RNAs. J Biol Chem 278:5505–5508
Yi R, Qin Y, Macara IG, Cullen BR (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17:3011–3016
Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659
Kok KH, Ng MH, Ching YP, Jin DY (2007) Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA. J Biol Chem 282:17649–17657
Ameres SL, Martinez J, Schroeder R (2007) Molecular basis for target RNA recognition and cleavage by human RISC. Cell 130:101–112
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854
Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834–838
Inui M, Martello G, Piccolo S (2010) MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 11:252–263
O’Shea JJ, Plenge R (2012) JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 36:542–550
Schneider WM, Chevillotte MD, Rice CM (2014) Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol 32:513–545
Shuai K, Liu B (2003) Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 3:900–911
Croker BA, Kiu H, Nicholson SE (2008) SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 19:414–422
Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, Rudensky AY (2009) Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30:80–91
Zawislak CL, Beaulieu AM, Loeb GB, Karo J, Canner D, Bezman NA, Lanier LL, Rudensky AY, Sun JC (2013) Stage-specific regulation of natural killer cell homeostasis and response against viral infection by microRNA-155. Proc Natl Acad Sci USA 110:6967–6972
Wang P, Hou J, Lin L, Wang C, Liu X, Li D, Ma F, Wang Z, Cao X (2010) Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol 185:6226–6233
Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED (2010) MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res 70:3119–3127
Yan XL, Jia YL, Chen L, Zeng Q, Zhou JN, Fu CJ, Chen HX, Yuan HF, Li ZW, Shi L, Xu YC, Wang JX, Zhang XM, He LJ, Zhai C, Yue W, Pei XT (2013) Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis. Hepatology 57:2274–2286
Kobayashi N, Uemura H, Nagahama K, Okudela K, Furuya M, Ino Y, Ito Y, Hirano H, Inayama Y, Aoki I, Nagashima Y, Kubota Y, Ishiguro H (2012) Identification of miR-30d as a novel prognostic maker of prostate cancer. Oncotarget 3:1455–1471
Li A, Song W, Qian J, Li Y, He J, Zhang Q, Li W, Zhai A, Kao W, Hu Y, Li H, Wu J, Ling H, Zhong Z, Zhang F (2013) MiR-122 modulates type I interferon expression through blocking suppressor of cytokine signaling 1. Int J Biochem Cell Biol 45:858–865
Zhou H, Hasni SA, Perez P, Tandon M, Jang SI, Zheng C, Kopp JB, Austin H 3rd, Balow JE, Alevizos I, Illei GG (2013) miR-150 promotes renal fibrosis in lupus nephritis by downregulating SOCS1. J Am Soc Nephrol 24:1073–1087
Pichiorri F, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, Taccioli C, Zanesi N, Alder H, Hagan JP, Munker R, Volinia S, Boccadoro M, Garzon R, Palumbo A, Aqeilan RI, Croce CM (2008) MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci USA 105:12885–12890
Qin S, Ai F, Ji WF, Rao W, Zhang HC, Yao WJ (2013) miR-19a promotes cell growth and tumorigenesis through targeting SOCS1 in gastric cancer. Asian Pac J Cancer Prev 14:835–840
Collins AS, McCoy CE, Lloyd AT, O’Farrelly C, Stevenson NJ (2013) miR-19a: an effective regulator of SOCS3 and enhancer of JAK-STAT signalling. PLoS ONE 8:e69090
Gantier MP, Stunden HJ, McCoy CE, Behlke MA, Wang D, Kaparakis-Liaskos M, Sarvestani ST, Yang YH, Xu D, Corr SC, Morand EF, Williams BR (2012) A miR-19 regulon that controls NF-κB signaling. Nucleic Acids Res 40:8048–8058
Zhai A, Qian J, Kao W, Li A, Li Y, He J, Zhang Q, Song W, Fu Y, Wu J, Chen X, Li H, Zhong Z, Ling H, Zhang F (2013) Borna disease virus encoded phosphoprotein inhibits host innate immunity by regulating miR-155. Antiviral Res 98:66–75
Ru P, Steele R, Hsueh EC, Ray RB (2011) Anti-miR-203 upregulates SOCS3 expression in breast cancer cells and enhances cisplatin chemosensitivity. Genes Cancer 2:720–727
Moffatt CE, Lamont RJ (2011) Porphyromonas gingivalis induction of microRNA-203 expression controls suppressor of cytokine signaling 3 in gingival epithelial cells. Infect Immun 79:2632–2637
Kneitz B, Krebs M, Kalogirou C, Schubert M, Joniau S, van Poppel H, Lerut E, Kneitz S, Scholz CJ, Ströbel P, Gessler M, Riedmiller H, Spahn M (2014) Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3. Cancer Res 74:2591–2603
Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20
Shuai K, Liu B (2005) Regulation of gene-activation pathways by PIAS proteins in the immune system. Nat Rev Immunol 5:593–605
Brock M, Trenkmann M, Gay RE, Gay S, Speich R, Huber LC (2011) MicroRNA-18a enhances the interleukin-6-mediated production of the acute-phase proteins fibrinogen and haptoglobin in human hepatocytes. J Biol Chem 286:40142–40150
Wu W, Takanashi M, Borjigin N, Ohno SI, Fujita K, Hoshino S, Osaka Y, Tsuchida A, Kuroda M (2013) MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis. Br J Cancer 108:653–661
Xiong Q, Zhong Q, Zhang J, Yang M, Li C, Zheng P, Bi LJ, Ge F (2012) Identification of novel miR-21 target proteins in multiple myeloma cells by quantitative proteomics. J Proteome Res 11:2078–2090
Shi L, Wan Y, Sun G, Zhang S, Wang Z, Zeng Y (2014) miR-125b inhibitor may enhance the invasion-prevention activity of temozolomide in glioblastoma stem cells by targeting PIAS3. BioDrugs 28:41–54
Mycko MP, Cichalewska M, Machlanska A, Cwiklinska H, Mariasiewicz M, Selmaj KW (2012) MicroRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination. Proc Natl Acad Sci USA 109:E1248–E1257
Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM (2005) Animal microRNAs confer robustness to gene expression and have a significant impact on 3′ UTR evolution. Cell 123:1133–1146
Napetschnig J, Wu H (2013) Molecular basis of NF-κB signaling. Annu Rev Biophys 42:443–468
Vallabhapurapu S, Karin M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27:693–733
Sun SC (2011) Non-canonical NF-κB signaling pathway. Cell Res 21:71–85
Hayden MS, Ghosh S (2008) Shared principles in NF-kappaB signaling. Cell 132:344–362
Su JL, Chen PB, Chen YH, Chen SC, Chang YW, Jan YH, Cheng X, Hsiao M, Hung MC (2010) Downregulation of microRNA miR-520h by E1A contributes to anticancer activity. Cancer Res 70:5096–5108
Yu YH, Chen HA, Chen PS, Cheng YJ, Hsu WH, Chang YW, Chen YH, Jan Y, Hsiao M, Chang TY, Liu YH, Jeng YM, Wu CH, Huang MT, Su YH, Hung MC, Chien MH, Chen CY, Kuo ML, Su JL (2013) MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol. Oncogene 32:431–443
Liu X, Sempere LF, Ouyang H, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Invest 120:1298–1309
Mavrakis KJ, Wolfe AL, Oricchio E, Palomero T, de Keersmaecker K, McJunkin K, Zuber J, James T, Khan AA, Leslie CS, Parker JS, Paddison PJ, Tam W, Ferrando A, Wendel HG (2010) Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 12:372–379
Belevych AE, Sansom SE, Terentyeva R, Ho HT, Nishijima Y, Martin MM, Jindal HK, Rochira JA, Kunitomo Y, Abdellatif M, Carnes CA, Elton TS, Györke S, Terentyev D (2011) MicroRNA-1 and -133 increase arrhythmogenesis in heart failure by dissociating phosphatase activity from RyR2 complex. PLoS ONE 6:e28324
Chen J, Chen ZJ (2013) Regulation of NF-κB by ubiquitination. Curr Opin Immunol 25:4–12
Sebban H, Yamaoka S, Courtois G (2006) Posttranslational modifications of NEMO and its partners in NF-kappaB signaling. Trends Cell Biol 16:569–577
Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K (2010) STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 39:493–506
Takiuchi D, Eguchi H, Nagano H, Iwagami Y, Tomimaru Y, Wada H, Kawamoto K, Kobayashi S, Marubashi S, Tanemura M, Mori M, Doki Y (2013) Involvement of microRNA-181b in the gemcitabine resistance of pancreatic cancer cells. Pancreatology 13:517–523
Xia JT, Chen LZ, Jian WH, Wang KB, Yang YZ, He WL, He YL, Chen D, Li W (2014) MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-κB signaling. J Transl Med 12:33
Song L, Liu L, Wu Z, Li Y, Ying Z, Lin C, Wu J, Hu B, Cheng SY, Li M, Li J (2012) TGF-β induces miR-182 to sustain NF-κB activation in glioma subsets. J Clin Invest 122:3563–3578
Song L, Lin C, Gong H, Wang C, Liu L, Wu J, Tao S, Hu B, Cheng SY, Li M, Li J (2013) miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops. Cell Res 23:274–289
Hymowitz SG, Wertz IE (2010) A20: from ubiquitin editing to tumour suppression. Nat Rev Cancer 10:332–341
Ye H, Liu X, Lv M, Wu Y, Kuang S, Gong J, Yuan P, Zhong Z, Li Q, Jia H, Sun J, Chen Z, Guo AY (2012) MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia. Nucleic Acids Res 40:5201–5214
Stewart CR, Marsh GA, Jenkins KA, Gantier MP, Tizard ML, Middleton D, Lowenthal JW, Haining J, Izzard L, Gough TJ, Deffrasnes C, Stambas J, Robinson R, Heine HG, Pallister JA, Foord AJ, Bean AG, Wang LF (2013) Promotion of Hendra virus replication by microRNA 146a. J Virol 87:3782–3791
Trenkmann M, Brock M, Gay RE, Michel BA, Gay S, Huber LC (2013) Tumor necrosis factor α-induced microRNA-18a activates rheumatoid arthritis synovial fibroblasts through a feedback loop in NF-κB signaling. Arthritis Rheum 65:916–927
Thounaojam MC, Kaushik DK, Kundu K, Basu A (2014) MicroRNA-29b modulates Japanese encephalitis virus-induced microglia activation by targeting tumor necrosis factor alpha-induced protein 3. J Neurochem 129:143–154
Wang CM, Wang Y, Fan CG, Xu FF, Sun WS, Liu YG, Jia JH (2011) miR-29c targets TNFAIP3, inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma. Biochem Biophys Res Commun 411:586–592
Balkhi MY, Iwenofu OH, Bakkar N, Ladner KJ, Chandler DS, Houghton PJ, London CA, Kraybill W, Perrotti D, Croce CM, Keller C, Guttridge DC (2013) miR-29 acts as a decoy in sarcomas to protect the tumor suppressor A20 mRNA from degradation by HuR. Sci Signal 6:ra63
Graff JW, Dickson AM, Clay G, McCaffrey AP, Wilson ME (2012) Identifying functional microRNAs in macrophages with polarized phenotypes. J Biol Chem 287:21816–21825
Kim SW, Ramasamy K, Bouamar H, Lin AP, Jiang D, Aguiar RC (2012) MicroRNAs miR-125a and miR-125b constitutively activate the NF-κB pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). Proc Natl Acad Sci USA 109:7865–7870
Weiss A, Attisano L (2013) The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol 2:47–63
Travis MA, Sheppard D (2014) TGF-β activation and function in immunity. Annu Rev Immunol 32:51–82
Massagué J (2012) TGFβ signalling in context. Nat Rev Mol Cell Biol 13:616–630
Marquez RT, Bandyopadhyay S, Wendlandt EB, Keck K, Hoffer BA, Icardi MS, Christensen RN, Schmidt WN, McCaffrey AP (2010) Correlation between microRNA expression levels and clinical parameters associated with chronic hepatitis C viral infection in humans. Lab Invest 90:1727–1736
Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminski N, Abraham E (2010) miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 207:1589–1597
Yamada M, Kubo H, Ota C, Takahashi T, Tando Y, Suzuki T, Fujino N, Makiguchi T, Takagi K, Suzuki T, Ichinose M (2013) The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells. Respir Res 14:95
Wang JY, Gao YB, Zhang N, Zou DW, Wang P, Zhu ZY, Li JY, Zhou SN, Wang SC, Wang YY, Yang JK (2014) miR-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropathy. Mol Cell Endocrinol 392:163–172
Zhong X, Chung AC, Chen HY, Dong Y, Meng XM, Li R, Yang W, Hou FF, Lan HY (2013) miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia 56:663–674
Zhu H, Li Y, Qu S, Luo H, Zhou Y, Wang Y, Zhao H, You Y, Xiao X, Zuo X (2012) MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma. J Clin Immunol 32:514–522
Zhu H, Luo H, Li Y, Zhou Y, Jiang Y, Chai J, Xiao X, You Y, Zuo X (2013) MicroRNA-21 in scleroderma fibrosis and its function in TGF-β-regulated fibrosis-related genes expression. J Clin Immunol 33:1100–1109
Chen L, Li Y, Fu Y, Peng J, Mo MH, Stamatakos M, Teal CB, Brem RF, Stojadinovic A, Grinkemeyer M, McCaffrey TA, Man YG, Fu SW (2013) Role of deregulated microRNAs in breast cancer progression using FFPE tissue. PLoS ONE 8:e54213
Li Q, Zhang D, Wang Y, Sun P, Hou X, Larner J, Xiong W, Mi J (2013) MiR-21/Smad 7 signaling determines TGF-β1-induced CAF formation. Sci Rep 3:2038
Bhagat TD, Zhou L, Sokol L, Kessel R, Caceres G, Gundabolu K, Tamari R, Gordon S, Mantzaris I, Jodlowski T, Yu Y, Jing X, Polineni R, Bhatia K, Pellagatti A, Boultwood J, Kambhampati S, Steidl U, Stein C, Ju W, Liu G, Kenny P, List A, Bitzer M, Verma A (2013) miR-21 mediates hematopoietic suppression in MDS by activating TGF-β signaling. Blood 121:2875–2881
Xia H, Ooi LL, Hui KM (2013) MicroRNA-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology 58:629–641
Chang Y, Liu C, Yang J, Liu G, Feng F, Tang J, Hu L, Li L, Jiang F, Chen C, Wang R, Yang Y, Jiang X, Wu M, Chen L, Wang H (2013) MiR-20a triggers metastasis of gallbladder carcinoma. J Hepatol 59:518–527
Parikh A, Lee C, Joseph P, Marchini S, Baccarini A, Kolev V, Romualdi C, Fruscio R, Shah H, Wang F, Mullokandov G, Fishman D, D’Incalci M, Rahaman J, Kalir T, Redline RW, Brown BD, Narla G, DiFeo A (2014) microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. Nat Commun 5:2977
Smith AL, Iwanaga R, Drasin DJ, Micalizzi DS, Vartuli RL, Tan AC, Ford HL (2012) The miR-106b-25 cluster targets Smad7, activates TGF-β signaling, and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer. Oncogene 31:5162–5171
Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H, Wang W, Zhang L, Zhang X, Tang Q, Zhang C, Tao J, Wang X, Gao X (2013) MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett 335:168–174
Li Y, Wang H, Li J, Yue W (2014) MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7. Acta Biochim Biophys Sin (Shanghai) 46:48–55
Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S, Gelinas R, Batte K, Yu L, Nuovo G, Galas D, Diaz P, Wang K, Nana-Sinkam SP (2012) Gene expression networks in COPD: microRNA and mRNA regulation. Thorax 67:122–131
David D, Nair SA, Pillai MR (2013) Smurf E3 ubiquitin ligases at the cross roads of oncogenesis and tumor suppression. Biochim Biophys Acta 1835:119–128
Cao S, Xiao L, Rao JN, Zou T, Liu L, Zhang D, Turner DJ, Gorospe M, Wang JY (2014) Inhibition of Smurf2 translation by miR-322/503 modulates TGF-β/Smad2 signaling and intestinal epithelial homeostasis. Mol Biol Cell 25:1234–1243
Liu X, Gu X, Sun L, Flowers AB, Rademaker AW, Zhou Y, Kiyokawa H (2014) Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: involvement of the RB-microRNA axis. BMC Cancer 14:57
Vimalraj S, Partridge NC, Selvamurugan N (2014) A positive role of microRNA-15b on regulation of osteoblast differentiation. J Cell Physiol 229:1236–1244
Liu Y, Liu W, Hu C, Xue Z, Wang G, Ding B, Luo H, Tang L, Kong X, Chen X, Liu N, Ding Y, Jin Y (2011) MiR-17 modulates osteogenic differentiation through a coherent feed-forward loop in mesenchymal stem cells isolated from periodontal ligaments of patients with periodontitis. Stem Cells 29:1804–1816
Wang W, Ren F, Wu Q, Jiang D, Li H, Peng Z, Wang J, Shi H (2014) MicroRNA-497 inhibition of ovarian cancer cell migration and invasion through targeting of SMAD specific E3 ubiquitin protein ligase 1. Biochem Biophys Res Commun 449:432–437
Edwards JP, Fujii H, Zhou AX, Creemers J, Unutmaz D, Shevach EM (2013) Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation. J Immunol 190:5506–5515
Zhou Q, Haupt S, Prots I, Thümmler K, Kremmer E, Lipsky PE, Schulze-Koops H, Skapenko A (2013) miR-142-3p is involved in CD25+ CD4 T cell proliferation by targeting the expression of glycoprotein A repetitions predominant. J Immunol 190:6579–6588
Luo JH (2011) Oncogenic activity of MCM7 transforming cluster. World J Clin Oncol 2:120–124
Baskerville S, Bartel DP (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11:241–247
Petrocca F, Vecchione A, Croce CM (2008) Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor β signaling. Cancer Res 68:8191–8194
Matsumura I, Tanaka H, Kanakura Y (2003) E2F1 and c-Myc in cell growth and death. Cell Cycle 2:333–338
Zhang Z, Qin YW, Brewer G, Jing Q (2012) MicroRNA degradation and turnover: regulating the regulators. Wiley Interdiscip Rev RNA 3:593–600
Berezikov E (2011) Evolution of microRNA diversity and regulation in animals. Nat Rev Genetics 12:846–860
Backes C, Meese E, Lenhof HP, Keller A (2010) A dictionary on microRNAs and their putative target pathways. Nucl Acids Res 38:4476–4486
Lindow M, Kauppinen S (2012) Discovering the first microRNA-targeted drug. J Cell Biol 199:407–412
Bouchie A (2013) First microRNA mimic enters clinic. Nat Biotechnol 31:577
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Lui, PY., Jin, DY. & Stevenson, N.J. MicroRNA: master controllers of intracellular signaling pathways. Cell. Mol. Life Sci. 72, 3531–3542 (2015). https://doi.org/10.1007/s00018-015-1940-0
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DOI: https://doi.org/10.1007/s00018-015-1940-0