Biogenesis and Regulation of Cardiovascular MicroRNAs

MicroRNAs (miRNAs) are important regulators of gene expression and fundamentally impact on cardiovascular function in health and disease. A tight control of miRNA expression is crucial for the maintenance of tissue homeostasis. However, a comprehensive understanding of the various levels of miRNA regulation is in its infancy. We here summarize the current knowledge about regulation of cardiovascular miRNAs at the transcriptional level by transcription factors, during processing by the Drosha and Dicer complexes and the importance of miRNA modification, editing, and decay mechanisms. As an example, miRNA regulation in diabetic and hypoxic cardiovascular disease conditions is discussed. Better knowledge about regulatory mechanisms of miRNAs in cardiovascular disease will probably lead to improved and novel miRNA-based therapeutic therapies.

[1]  H. Sukhwani,et al.  Processing , 1988 .

[2]  T. Thum,et al.  MicroRNA-based therapeutic approaches in the cardiovascular system. , 2012, Cardiovascular therapeutics.

[3]  Yanjie Lu,et al.  MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. , 2011, The Journal of Biological Chemistry.

[4]  T. Tuschl,et al.  MicroRNA-24 Regulates Vascularity After Myocardial Infarction , 2011, Circulation.

[5]  W. De,et al.  MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14) , 2011, Oncogene.

[6]  Jinqiao Qian,et al.  The role of microRNA in modulating myocardial ischemia-reperfusion injury. , 2011, Physiological genomics.

[7]  M. Muckenthaler,et al.  Signal transducer and activator of transcription 3-mediated regulation of miR-199a-5p links cardiomyocyte and endothelial cell function in the heart: a key role for ubiquitin-conjugating enzymes. , 2011, European heart journal.

[8]  M. Abdellatif,et al.  Thioredoxin 1 Negatively Regulates Angiotensin II–Induced Cardiac Hypertrophy Through Upregulation of miR-98/let-7 , 2011, Circulation research.

[9]  P. Linsley,et al.  Comparison of different miR-21 inhibitor chemistries in a cardiac disease model. , 2011, The Journal of clinical investigation.

[10]  P. Galuppo,et al.  Deletion of Cardiomyocyte Mineralocorticoid Receptor Ameliorates Adverse Remodeling After Myocardial Infarction , 2011, Circulation.

[11]  E. Olson,et al.  Pervasive roles of microRNAs in cardiovascular biology , 2011, Nature.

[12]  G. Condorelli,et al.  MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling , 2010, Nature Cell Biology.

[13]  V. Kim,et al.  Modifications of Small RNAs and Their Associated Proteins , 2010, Cell.

[14]  D. Patel,et al.  Phosphorylation of human Argonaute proteins affects small RNA binding , 2010, Nucleic acids research.

[15]  S. Kauppinen,et al.  Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. , 2010, The Journal of clinical investigation.

[16]  J. Bauersachs Regulation of Myocardial Fibrosis by MicroRNAs , 2010, Journal of cardiovascular pharmacology.

[17]  Sabita Roy,et al.  Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-α isoforms and promotes angiogenesis. , 2010, The Journal of clinical investigation.

[18]  Anil G Jegga,et al.  Synergistic effects of the GATA-4-mediated miR-144/451 cluster in protection against simulated ischemia/reperfusion-induced cardiomyocyte death. , 2010, Journal of molecular and cellular cardiology.

[19]  H. Nielsen,et al.  High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients , 2010, Clinical & Experimental Metastasis.

[20]  G. Ertl,et al.  Impairment of endothelial progenitor cell function and vascularization capacity by aldosterone in mice and humans , 2010, European heart journal.

[21]  T. Thum,et al.  Circulating MicroRNAs as Biomarkers and Potential Paracrine Mediators of Cardiovascular Disease , 2010, Circulation. Cardiovascular genetics.

[22]  B. Davis-Dusenbery,et al.  Mechanisms of control of microRNA biogenesis. , 2010, Journal of biochemistry.

[23]  P. Oettgen,et al.  Ets-1 and Ets-2 Regulate the Expression of MicroRNA-126 in Endothelial Cells , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[24]  M. Medvedovic,et al.  MicroRNA-494 Targeting Both Proapoptotic and Antiapoptotic Proteins Protects Against Ischemia/Reperfusion-Induced Cardiac Injury , 2010, Circulation.

[25]  V. Regitz-Zagrosek,et al.  Differential Cardiac Remodeling in Preload Versus Afterload , 2010, Circulation.

[26]  W. Filipowicz,et al.  The widespread regulation of microRNA biogenesis, function and decay , 2010, Nature Reviews Genetics.

[27]  You-yi Zhang,et al.  miR‐1/miR‐206 regulate Hsp60 expression contributing to glucose‐mediated apoptosis in cardiomyocytes , 2010, FEBS letters.

[28]  Chunxiang Zhang,et al.  Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. , 2010, Cardiovascular research.

[29]  S. Bronk,et al.  Transcriptional suppression of mir‐29b‐1/mir‐29a promoter by c‐Myc, hedgehog, and NF‐kappaB , 2010, Journal of cellular biochemistry.

[30]  Thomas Thum,et al.  MicroRNA-21: from cancer to cardiovascular disease. , 2010, Current drug targets.

[31]  Qingbo Xu,et al.  Short Communication: Asymmetric Dimethylarginine Impairs Angiogenic Progenitor Cell Function in Patients With Coronary Artery Disease Through a MicroRNA-21–Dependent Mechanism , 2010, Circulation research.

[32]  Danish Sayed,et al.  An antagonism between the AKT and beta-adrenergic signaling pathways mediated through their reciprocal effects on miR-199a-5p. , 2010, Cellular signalling.

[33]  J. Carroll,et al.  High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-κB-complex-dependent gene expression in human heart failure , 2010, Genome Medicine.

[34]  Stefanie Dimmeler,et al.  Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. , 2010, Blood.

[35]  G. Hannon,et al.  A dicer-independent miRNA biogenesis pathway that requires Ago catalysis , 2010, Nature.

[36]  S. Hammond,et al.  Emerging paradigms of regulated microRNA processing. , 2010, Genes & development.

[37]  Michael B. Stadler,et al.  Characterizing Light-Regulated Retinal MicroRNAs Reveals Rapid Turnover as a Common Property of Neuronal MicroRNAs , 2010, Cell.

[38]  Xin Huang,et al.  MiR-210--micromanager of the hypoxia pathway. , 2010, Trends in molecular medicine.

[39]  Chunxiang Zhang,et al.  MicroRNA-21 in Cardiovascular Disease , 2010, Journal of cardiovascular translational research.

[40]  N. Kaminski,et al.  miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis , 2010, The Journal of experimental medicine.

[41]  S. Tyagi,et al.  MMP-9 Gene Ablation and TIMP-4 Mitigate PAR-1-Mediated Cardiomyocyte Dysfunction: A Plausible Role of Dicer and miRNA , 2010, Cell Biochemistry and Biophysics.

[42]  Danish Sayed,et al.  MicroRNA-21 Is a Downstream Effector of AKT That Mediates Its Antiapoptotic Effects via Suppression of Fas Ligand* , 2010, The Journal of Biological Chemistry.

[43]  Zhe Li,et al.  Reciprocal Repression Between MicroRNA-133 and Calcineurin Regulates Cardiac Hypertrophy: A Novel Mechanism for Progressive Cardiac Hypertrophy , 2010, Hypertension.

[44]  R. Khanin,et al.  Dynamic Changes in Lung MicroRNA Profiles During the Development of Pulmonary Hypertension due to Chronic Hypoxia and Monocrotaline , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[45]  M. Febbraio,et al.  PI3K(p110&agr;) Protects Against Myocardial Infarction-Induced Heart Failure: Identification of PI3K-Regulated miRNA and mRNA , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[46]  E. Olson,et al.  MicroRNAs add a new dimension to cardiovascular disease. , 2010, Circulation.

[47]  R. Sperling,et al.  A novel tissue-specific alternatively spliced form of the A-to-I RNA editing enzyme ADAR2 , 2010, RNA biology.

[48]  B. Long,et al.  miR-9 and NFATc3 Regulate Myocardin in Cardiac Hypertrophy* , 2010, The Journal of Biological Chemistry.

[49]  Zhaoyong Hu,et al.  Downregulation of microRNA-29 by antisense inhibitors and a PPAR-gamma agonist protects against myocardial ischaemia-reperfusion injury. , 2010, Cardiovascular research.

[50]  E. Olson,et al.  Myocyte Enhancer Factor 2 and Class II Histone Deacetylases Control a Gender-Specific Pathway of Cardioprotection Mediated by the Estrogen Receptor , 2010, Circulation research.

[51]  C. Tabin,et al.  miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation , 2009, Proceedings of the National Academy of Sciences.

[52]  D. Catalucci,et al.  Reciprocal Regulation of MicroRNA-1 and Insulin-Like Growth Factor-1 Signal Transduction Cascade in Cardiac and Skeletal Muscle in Physiological and Pathological Conditions , 2009, Circulation.

[53]  E. Olson,et al.  A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. , 2009, Developmental cell.

[54]  Vijay G Divakaran,et al.  Adaptive and Maladptive Effects of SMAD3 Signaling in the Adult Heart After Hemodynamic Pressure Overloading , 2009, Circulation. Heart failure.

[55]  Ciro Indolfi,et al.  The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease , 2009, Cell Death and Differentiation.

[56]  Z. Paroo,et al.  Phosphorylation of the Human MicroRNA-Generating Complex Mediates MAPK/Erk Signaling , 2009, Cell.

[57]  H. Grosshans,et al.  Active turnover modulates mature microRNA activity in Caenorhabditis elegans , 2009, Nature.

[58]  E. Wang,et al.  Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize different CD34+ cell populations based on global gene and microRNA expression signatures. , 2009, Blood.

[59]  Johanna Schneider,et al.  Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. , 2009, The Journal of clinical investigation.

[60]  Michael T. McManus,et al.  LPS induces KH‐type splicing regulatory protein‐dependent processing of microRNA‐155 precursors in macrophages , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[61]  Shujia Jiang,et al.  Ischemic Preconditioning Augments Survival of Stem Cells via miR-210 Expression by Targeting Caspase-8-associated Protein 2* , 2009, The Journal of Biological Chemistry.

[62]  R. Jaenisch,et al.  Loss of Cardiac microRNA-Mediated Regulation Leads to Dilated Cardiomyopathy and Heart Failure , 2009, Circulation research.

[63]  D. Catalucci,et al.  MicroRNAs in Cardiovascular Biology and Heart Disease , 2009, Circulation. Cardiovascular genetics.

[64]  J. Yong,et al.  Ars2 Links the Nuclear Cap-Binding Complex to RNA Interference and Cell Proliferation , 2009, Cell.

[65]  P. Tam Faculty Opinions recommendation of miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. , 2009 .

[66]  Jianqin Jiao,et al.  miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy , 2009, Proceedings of the National Academy of Sciences.

[67]  K. Luebke Faculty Opinions recommendation of The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. , 2009 .

[68]  Stefanie Dimmeler,et al.  MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice , 2009, Science.

[69]  J. She,et al.  Tie2cre-induced inactivation of the miRNA-processing enzyme Dicer disrupts invariant NKT cell development , 2009, Proceedings of the National Academy of Sciences.

[70]  Shusheng Wang,et al.  AngiomiRs--key regulators of angiogenesis. , 2009, Current opinion in genetics & development.

[71]  Maureen A. Sartor,et al.  MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia/Reperfusion Injury by Targeting Heat-Shock Protein 20 , 2009, Circulation.

[72]  K. Nishigaki,et al.  Antidiabetic drug pioglitazone protects the heart via activation of PPAR-gamma receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction. , 2009, American journal of physiology. Heart and circulatory physiology.

[73]  S. Vatner,et al.  Downregulation of MiR-199a Derepresses Hypoxia-Inducible Factor-1α and Sirtuin 1 and Recapitulates Hypoxia Preconditioning in Cardiac Myocytes , 2009, Circulation research.

[74]  G. Nuovo,et al.  MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. , 2009, Cardiovascular research.

[75]  Yao‐Hua Song,et al.  MicroRNA-221 regulates high glucose-induced endothelial dysfunction. , 2009, Biochemical and biophysical research communications.

[76]  F. Salloum,et al.  A Novel Role of MicroRNA in Late Preconditioning: Upregulation of Endothelial Nitric Oxide Synthase and Heat Shock Protein 70 , 2009, Circulation research.

[77]  Chunxiang Zhang,et al.  A Necessary Role of miR-221 and miR-222 in Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia , 2009, Circulation research.

[78]  Xiaoying Wang,et al.  Endogenous microRNAs induced by heat‐shock reduce myocardial infarction following ischemia–reperfusion in mice , 2008, FEBS letters.

[79]  W. Rottbauer,et al.  MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts , 2008, Nature.

[80]  H. Matsubara,et al.  Downregulation of Dicer expression by serum withdrawal sensitizes human endothelial cells to apoptosis. , 2008, American journal of physiology. Heart and circulatory physiology.

[81]  E. Olson,et al.  microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. , 2008, Genes & development.

[82]  Yao‐Hua Song,et al.  Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1. , 2008, Biochemical and biophysical research communications.

[83]  D. Srivastava,et al.  Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart , 2008, Proceedings of the National Academy of Sciences.

[84]  Jun S. Song,et al.  Chromatin structure analyses identify miRNA promoters. , 2008, Genes & development.

[85]  Y. Pinto,et al.  Conditional Dicer Gene Deletion in the Postnatal Myocardium Provokes Spontaneous Cardiac Remodeling , 2008, Circulation.

[86]  T. Thum Cardiac dissonance without conductors: how dicer depletion provokes chaos in the heart. , 2008, Circulation.

[87]  Scott A Gerber,et al.  Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis , 2008, Proceedings of the National Academy of Sciences.

[88]  Jeffrey E. Thatcher,et al.  Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis , 2008, Proceedings of the National Academy of Sciences.

[89]  Thomas Thum,et al.  MicroRNAs: novel regulators in cardiac development and disease. , 2008, Cardiovascular research.

[90]  Terry Hyslop,et al.  A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation , 2008, The Journal of cell biology.

[91]  J. M. Thomson,et al.  Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. , 2008, RNA.

[92]  P. Fasanaro,et al.  MicroRNA-210 Modulates Endothelial Cell Response to Hypoxia and Inhibits the Receptor Tyrosine Kinase Ligand Ephrin-A3* , 2008, Journal of Biological Chemistry.

[93]  Paul Pavlidis,et al.  Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model , 2008, Nature Genetics.

[94]  W. Kaelin,et al.  Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. , 2008, Molecular cell.

[95]  Shuji Fujita,et al.  miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. , 2008, Journal of molecular biology.

[96]  R V Davuluri,et al.  A microRNA component of the hypoxic response , 2008, Cell Death and Differentiation.

[97]  Michael D. Schneider,et al.  Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure , 2008, Proceedings of the National Academy of Sciences.

[98]  A. van Hoof,et al.  Messenger RNA regulation: to translate or to degrade , 2008, The EMBO journal.

[99]  E. Olson,et al.  An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133 , 2007, Proceedings of the National Academy of Sciences.

[100]  D. Haber,et al.  Dual Role for Argonautes in MicroRNA Processing and Posttranscriptional Regulation of MicroRNA Expression , 2007, Cell.

[101]  R. Schwartz,et al.  Serum response factor micromanaging cardiogenesis. , 2007, Current opinion in cell biology.

[102]  D. Tsikas,et al.  Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-I. , 2007, The Journal of clinical endocrinology and metabolism.

[103]  J. Hackermüller,et al.  Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. , 2007, Blood.

[104]  J. Bauersachs,et al.  Endothelial progenitor cell dysfunction: mechanisms and therapeutic approaches , 2007, European journal of clinical investigation.

[105]  Leonard D. Goldstein,et al.  Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels , 2007, The Journal of pathology.

[106]  Stefanie Dimmeler,et al.  Role of Dicer and Drosha for Endothelial MicroRNA Expression and Angiogenesis , 2007, Circulation research.

[107]  S. Guil,et al.  The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a , 2007, Nature Structural &Molecular Biology.

[108]  Carlo M. Croce,et al.  MicroRNAs 17-5p–20a–106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation , 2007, Nature Cell Biology.

[109]  C. Croce,et al.  MicroRNA-133 controls cardiac hypertrophy , 2007, Nature Medicine.

[110]  B. O’Malley,et al.  DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs , 2007, Nature Cell Biology.

[111]  Xiaoxia Qi,et al.  Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA , 2007, Science.

[112]  Jordan S. Pober,et al.  Dicer Dependent MicroRNAs Regulate Gene Expression and Functions in Human Endothelial Cells , 2007, Circulation research.

[113]  Yanjie Lu,et al.  MicroRNA miR-133 Represses HERG K+ Channel Expression Contributing to QT Prolongation in Diabetic Hearts* , 2007, Journal of Biological Chemistry.

[114]  Michael T. McManus,et al.  Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2 , 2007, Cell.

[115]  P. Galuppo,et al.  Endothelial Nitric Oxide Synthase Uncoupling Impairs Endothelial Progenitor Cell Mobilization and Function in Diabetes , 2007, Diabetes.

[116]  P. Poole‐Wilson,et al.  Age-Dependent Impairment of Endothelial Progenitor Cells Is Corrected by Growth Hormone Mediated Increase of Insulin-Like Growth Factor-1 , 2007, Circulation research.

[117]  Vincent De Guire,et al.  An E2F/miR-20a Autoregulatory Feedback Loop* , 2007, Journal of Biological Chemistry.

[118]  J. M. Thomson,et al.  Direct Regulation of an Oncogenic Micro-RNA Cluster by E2F Transcription Factors* , 2007, Journal of Biological Chemistry.

[119]  E. Olson,et al.  A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure , 2006, Proceedings of the National Academy of Sciences.

[120]  P. Oettgen Regulation of vascular inflammation and remodeling by ETS factors. , 2006, Circulation research.

[121]  Anne Gatignol,et al.  TRBP, a regulator of cellular PKR and HIV‐1 virus expression, interacts with Dicer and functions in RNA silencing , 2005, EMBO reports.

[122]  P. Marsden,et al.  Extensive variation in the 5'-UTR of Dicer mRNAs influences translational efficiency. , 2005, Biochemical and biophysical research communications.

[123]  Yong Zhao,et al.  Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis , 2005, Nature.

[124]  M. E. Glasner,et al.  MicroRNAs Regulate Brain Morphogenesis in Zebrafish , 2005, Science.

[125]  B. Cullen,et al.  Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. , 2004, RNA.

[126]  R. Shiekhattar,et al.  The Microprocessor complex mediates the genesis of microRNAs , 2004, Nature.

[127]  Sanghyuk Lee,et al.  MicroRNA genes are transcribed by RNA polymerase II , 2004, The EMBO journal.

[128]  Jing Liu,et al.  Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy. , 2003, The Journal of clinical investigation.

[129]  C. Heeschen,et al.  Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells , 2003, Nature Medicine.

[130]  S. Elledge,et al.  Dicer is essential for mouse development , 2003, Nature Genetics.

[131]  Michael Z Michael,et al.  Reduced accumulation of specific microRNAs in colorectal neoplasia. , 2003, Molecular cancer research : MCR.

[132]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[133]  R. Schwartz,et al.  Hop Is an Unusual Homeobox Gene that Modulates Cardiac Development , 2002, Cell.

[134]  A. Pasquinelli,et al.  A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA , 2001, Science.

[135]  T. Münzel,et al.  Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus , 2001, Circulation research.

[136]  R. Kitsis,et al.  The MEK1–ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice , 2000, The EMBO journal.

[137]  Jeffrey Robbins,et al.  A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy , 1998, Cell.

[138]  T. Lee,et al.  Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal alpha-actin transcription in embryonic myoblasts. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[139]  K. Claffey,et al.  Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells. , 2009, Endocrinology.

[140]  A. Hata,et al.  SMAD proteins control DROSHA-mediated microRNA maturation , 2008, Nature.

[141]  Martin J. Simard,et al.  Argonaute proteins: key players in RNA silencing , 2008, Nature Reviews Molecular Cell Biology.