Micro RNAs: an arguable appraisal in medicine

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Micro RNAs (miRNAs) represent a newly discovered class of regulatory molecules in the human body. miRNA is a short double stranded RNA sequence interfering with mRNA, causing in most cases, inhibition of translation. Synthesis of miRNAs shows an increasing developmental pattern and postnatally miRNAs are synthesized in all cells possessing transcriptional machinery. miRNAs usually target several mRNAs and therefore conclusive evidences proving their functions are not always ease to be acquired. In spite of this difficulty, functions of miRNAs were firmly established in the development, the cardiovascular and neural diseases, and cancer. Many miRNAs have been reported to be associated with physiological state of cells and/or tissues. This finding becomes fundamental, especially when consider that these miRNAs can be released from cell into intracellular space or circulation. Correlation between miRNA production in tissues and its contribution to multisource miRNA pool in the circulation is in a focus of biomarker-oriented researchers. Recently, circulating miRNAs have been suggested to be applicable as biomarkers in several types of cancer, cardiovascular injury, and diabetes. Role of miRNAs in the organism intercellular signaling is still under the broad investigation. Several miRNA mimics, intended for treatment of disease, are being currently tested in the clinical trials.

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  • Abdalla MA Haj-Ahmad Y. Promising Candidate Urinary MicroRNA Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients. J Cancer 3 19-31 2012. http://dx.doi.org/10.7150/jca.3.19

  • Adachi T Nakanishi M Otsuka Y Nishimura K Hirokawa G Goto Y Nonogi H Iwai N. Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem 56 1183-1185 2010. http://dx.doi.org/10.1373/clinchem.2010.144121

  • Adams BD Furneaux H White BA. Th e micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor- alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol 21 1132-1147 2007. http://dx.doi.org/10.1210/me.2007-0022

  • Aguado-Fraile E Ramos E Conde E Rodriguez M Martin-Gomez L Lietor A Candela A Ponte B Lia-o F Garcia- Bermejo ML. A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury. PLoS One 10 e0127175 2015. http://dx.doi.org/10.1371/journal.pone.0127175

  • Arroyo JD Chevillet JR Kroh EM Ruf IK Pritchard CC Gibson DF Mitchell PS Bennett CF Pogosova-Agadjanyan EL Stirewalt DL Tait JF Tewari M. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108 5003-5008 2011. http://dx.doi.org/10.1073/pnas.1019055108

  • Asangani IA Rasheed SA Nikolova DA Leupold JH Colburn NH Post S Allgayer H. MicroRNA-21 (miR-21) posttranscriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion intravasation and metastasis in colorectal cancer. Oncogene 27 2128-2136 2008. http://dx.doi.org/10.1038/sj.onc.1210856

  • Baier SR Nguyen C Xie F Wood JR Zempleni J. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells HEK-293 kidney cell cultures and mouse livers. J Nutr 144 1495-1500 2014. http://dx.doi.org/10.3945/jn.114.196436

  • Basati G Razavi AE Pakzad I Malayeri FA. Circulating levels of the miRNAs miR-194 and miR-29b as clinically useful biomarkers for colorectal cancer. Tumour Biol [Epub ahead of print] 2015.

  • Brase JC Johannes M Schlomm T Falth M Haese A Steuber T Beissbarth T Kuner R Sultmann H. Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 128 608-616 2011. http://dx.doi.org/10.1002/ijc.25376

  • Chen X Ba Y Ma L Cai X Yin Y Wang K Guo J Zhang Y Chen J Guo X Li Q Li X Wang W Zhang Y Wang J Jiang X Xiang Y Xu C Zheng P Zhang J Li R Zhang H Shang X Gong T Ning G Wang J Zen K Zhang J Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18 997-1006 2008. http://dx.doi.org/10.1038/cr.2008.282

  • Cheng H Zhang L Cogdell DE Zheng H Schetter AJ Nykter M Harris CC Chen K Hamilton SR Zhang W. Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS One 6 e17745 2011. http://dx.doi.org/10.1371/journal.pone.0017745

  • Chim SS Shing TK Hung EC Leung TY Lau TK Chiu RW Lo YM. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem 54 482-490 2008. http://dx.doi.org/10.1373/clinchem.2007.097972

  • Corbin R Olsson-Carter K Slack F. Th e role of microRNAs in synaptic development and function. BMB Rep 42 131-135 2009. http://dx.doi.org/10.5483/BMBRep.2009.42.3.131

  • Cottonham CL Kaneko S Xu L. miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells. J Biol Chem 285 35293-35302 2010. http://dx.doi.org/10.1074/jbc.M110.160069

  • Creighton CJ Fountain MD Yu Z Nagaraja AK Zhu H Khan M Olokpa E Zariff A Gunaratne PH Matzuk MM Anderson ML. Molecular Profiling Uncovers a p53-Associated Role for MicroRNA-31 in Inhibiting the Proliferation of Serous Ovarian Carcinomas and Other Cancers. Cancer Res 70 1906−1915 2010. http://dx.doi.org/10.1158/0008-5472.CAN-09-3875

  • Daige CL Wiggins JF Priddy L Nelligan-Davis T Zhao J Brown D. Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer. Mol. Cancer Th er 13 2352-2360 2014. http://dx.doi.org/10.1158/1535-7163.MCT-14-0209

  • Davis ME Zuckerman JE Choi CH Seligson D Tolcher A Alabi CA Yen Y Heidel JD Ribas A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464 1067-1070 2010. http://dx.doi.org/10.1038/nature08956

  • Deng Y Wang CC Choy KW Du Q Chen J Wang Q Li L Chung TK Tang T. Th erapeutic potentials of gene silencing by RNA interference: principles challenges and new strategies. Genes 538 217−227 2014. http://dx.doi.org/10.1016/j.gene.2013.12.019

  • Devalliere J Chang WG Andrejecsk JW Abrahimi P Cheng CJ Jane-wit D Saltzman WM Pober JS. Sustained delivery of proangiogenic microRNA-132 by nanoparticle transfection improves endothelial cell transplantation. FASEB J 28 908−922 2014. http://dx.doi.org/10.1096/fj.13-238527

  • DeVincenzo J Lambkin-Williams R Wilkinson T Cehelsky J Nochur S Walsh E Meyers R Gollob J Vaishnaw A. A randomized double-blind placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci U S A 107 8800 2010. http://dx.doi.org/10.1073/pnas.0912186107

  • Elbashir SM Harborth J Lendeckel W Yalcin A Weber K Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411 494−498 2001. http://dx.doi.org/10.1038/35078107

  • Escrevente C Keller S Altevogt P Costa J. Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer 11 108 2011. http://dx.doi.org/10.1186/1471-2407-11-108

  • Etheridge A Lee I Hood L Galas D Wang K. Extracellular microRNA: a new source of biomarkers. Mutat Res 717 85−90 2011. http://dx.doi.org/10.1016/j.mrfmmm.2011.03.004

  • Fang Z Tang J Bai Y Lin H You H Jin H Lin L You P Li J Dai Z Liang X Su Y Hu Q Wang F Zhang ZY. Plasma levels of microRNA-24 microRNA-320a and microRNA-423-5p are potential biomarkers for colorectal carcinoma. J Exp Clin Cancer Res 34 86 2015. http://dx.doi.org/10.1186/s13046-015-0198-6

  • Ferreira R Santos T Amar A Gong A Chen TC Tahara SM Giannotta SL Hofman FM. Argonaute-2 promotes miR-18a entry in human brain endothelial cells. J Am Heart Assoc 3 e000968 2014. http://dx.doi.org/10.1161/JAHA.114.000968

  • Garber KB Visootsak J Warren ST. Fragile X syndrome. Eur J Hum Genet 16 666−672 2008. http://dx.doi.org/10.1038/ejhg.2008.61

  • Gavrilov K Saltzman WM. Therapeutic siRNA: principles challenges and strategies. Yale J Biol Med 85 187−200 2012.

  • Hanke M Hoefig K Merz H Feller AC Kausch I Jocham D Warnecke JM Sczakiel G. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol 28 655-661 2009. http://dx.doi.org/10.1016/j.urolonc.2009.01.027

  • Harfe BD McManus MT Mansfield JH Hornstein E Tabin CJ. Th e RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102 10898-10903 2005. http://dx.doi.org/10.1073/pnas.0504834102

  • Harris TA Yamakuchi M Ferlito M Mendell JT Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 105 1516-1521 2008. http://dx.doi.org/10.1073/pnas.0707493105

  • Hatley ME Patrick DM Garcia MR Richardson JA Bassel-Duby R van Rooij E Olson EN. Modulation of K-Rasdependent lung tumorigenesis by MicroRNA-21. Cancer Cell 18 282−293 2010. http://dx.doi.org/10.1016/j.ccr.2010.08.013

  • Hebert SS Horre K Nicolai L Papadopoulou AS Mandemakers W Silahtaroglu AN Kauppinen S Delacourte A De Strooper B. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci U S A 105 6415−6420 2008. http://dx.doi.org/10.1073/pnas.0710263105

  • Hornby RJ Starkey Lewis P Dear J Goldring C Park BK. MicroRNAs as potential circulating biomarkers of druginduced liver injury: key current and future issues for translation to humans. Expert Rev Clin Pharmacol 7 349−362 2014. http://dx.doi.org/10.1586/17512433.2014.904201

  • Hrustincova A Votavova H Dostalova Merkerova M. Circulating MicroRNAs: Methodological Aspects in Detection of Th ese Biomarkers.Folia Biologica (Praha) 61 203−218 2015.

  • Hydbring P Badalian-Very G. Clinical applications of microRNAs. F1000Research 2 136 2013. http://dx.doi.org/10.12688/f1000research.2-136.v1

  • Ishizuka A Siomi MCSiomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev 16 2497−2508 2002. http://dx.doi.org/10.1101/gad.1022002

  • Janssen HL Reesink HW Lawitz EJ Zeuzem S Rodriguez-Torres M Patel K van der Meer AJ Patick AK Chen A Zhou Y Persson R King BD Kauppinen S Levin AA Hodges MR. Treatment of HCV infection by targeting microRNA. N Engl J Med 368 1685-1694 2013. http://dx.doi.org/10.1056/NEJMoa1209026

  • Ji R Cheng Y Yue J Yang J Liu X Chen H Dean DB Zhang C. MicroRNA expression signature and antisensemediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 100 1579-1588 2007. http://dx.doi.org/10.1161/CIRCRESAHA.106.141986

  • Ji X Takahashi R Hiura Y Hirokawa G Fukushima Y Iwai N. Plasma miR-208 as a biomarker of myocardial injury. Clin Chem 55 1944-1949 2009. http://dx.doi.org/10.1373/clinchem.2009.125310

  • Johnson SM Grosshans H Shingara J Byrom M Jarvis R Cheng A Labourier E Reinert KL Brown D Slack FJ. RAS is regulated by the let-7 microRNA family. Cell 120 635−647 2005. http://dx.doi.org/10.1016/j.cell.2005.01.014

  • Jose AM. Movement of regulatory RNA between animal cells. Genesis 53 395−416 2015. http://dx.doi.org/10.1002/dvg.22871

  • Kanellopoulou C Muljo SA Kung AL Ganesan S Drapkin R Jenuwein T Livingston DM Rajewsky K. Dicerdeficient mouse embryonic stem cells are defective in diff erentiation and centromeric silencing. Genes Dev 19 489-501 2005. http://dx.doi.org/10.1101/gad.1248505

  • Karolina DS Tavintharan S Armugam A Sepramaniam S Pek SL Wong MT Lim SC Sum CF Jeyaseelan K. Circulating miRNA profiles in patients with metabolic syndrome. J Clin Endocrinol Metab 97 E2271-E2276 2012. http://dx.doi.org/10.1210/jc.2012-1996

  • Karube Y Tanaka H Osada H Tomida S Tatematsu Y Yanagisawa K Yatabe Y Takamizawa J Miyoshi S Mitsudomi T Takahashi T. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci 96 111-115 2005. http://dx.doi.org/10.1111/j.1349

  • Katsuda T Kosaka N Ochiya T. Th e roles of extracellular vesicles in cancer biology: toward the development of novel cancer biomarkers. Proteomics 14 412−425 2014. http://dx.doi.org/10.1002/pmic.201300389

  • Kim HS Lee KS Bae HJ Eun JW Shen Q Park SJ Shin WC Yang HD Park M Park WS Kang YK Nam SW. MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer. Oncotarget 6 8089-8102 2015. http://dx.doi.org/10.18632/oncotarget.3512

  • Kiriakidou M Nelson PT Kouranov A Fitziev P Bouyioukos C Mourelatos Z Hatzigeorgiou A. A combined computational-experimental approach predicts human microRNA targets. Genes Dev 18 1165−1178 2004. http://dx.doi.org/10.1101/gad.1184704

  • Koldehoff M Steckel NK Beelen DW Elmaagacli AH. Th erapeutic application of small interfering RNA directed against bcr-abl transcripts to a patient with imatinib-resistant chronic myeloid leukaemia. Clin Exp Med 7 47−55 2007. http://dx.doi.org/10.1007/s10238-007-0125-z

  • Kole AJ Swahari V Hammond SM Deshmukh M. miR-29b is activated during neuronal maturation and targets BH3-only genes to restrict apoptosis. Genes Dev 25 125−130 2011. http://dx.doi.org/10.1101/gad.1975411

  • Kosaka N Iguchi H Yoshioka Y Takeshita F Matsuki Y Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285 17442−17452 2010. http://dx.doi.org/10.1074/jbc.M110.107821

  • Koumangoye RB Sakwe AM Goodwin JS Patel T Ochieng J. Detachment of breast tumor cells induces rapid secretion of exosomes which subsequently mediate cellular adhesion and spreading. PLoS One 6 e24234 2011. http://dx.doi.org/10.1371/journal.pone.0024234

  • Kuehbacher A Urbich C Zeiher AM Dimmeler S. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res 101 59-68 2007. http://dx.doi.org/10.1161/CIRCRESAHA.107.153916

  • Kumar MS Erkeland SJ Pester RE Chen CY Ebert MS Sharp PA Jacks T. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A 105 3903−3908 2008. http://dx.doi.org/10.1073/pnas.0712321105

  • Lagos-Quintana M Rauhut R Yalcin A Meyer J Lendeckel W Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol 12 735-739 2002. http://dx.doi.org/10.1016/S0960-9822(02)00809-6

  • Lam JKW Chow MYT Zhang Y Leung SWS. siRNA Versus miRNA as Therapeutics for Gene Silencing. Mol Th er Nucleic Acids 4 e252 2015. http://dx.doi.org/10.1038/mtna.2015.23

  • Lee RC Feinbaum RL Ambros V. Th e C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75 843-854 1993. http://dx.doi.org/10.1016/0092-8674(93)90529-Y

  • Lee KH Kim SH Lee HR Kim W Kim DY Shin JC Yoo SH Kim KT. MicroRNA-185 oscillation controls circadian amplitude of mouse Cryptochrome 1 via translational regulation. Mol Biol Cell 24 2248-2255 2013. http://dx.doi.org/10.1091/mbc.E12-12-0849

  • Li Y Fan L Liu S Liu W Zhang H Zhou T Wu D Yang P Shen L Chen J Jin Y. Th e promotion of bone regeneration through positive regulation of angiogenic-osteogenic coupling using microRNA-26a. Biomaterials. 34 5048-5058 2013. http://dx.doi.org/10.1016/j.biomaterials.2013.03.052

  • Li H Cheng Wu C Aramayo R Sachs MS Harlowa ML. Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA). Sci Rep 5 14918 2015. http://dx.doi.org/10.1038/srep14918

  • Liang G Zhu Y Sun B Shao Y Jing A Wang J Xiao Z. Assessing the survival of exogenous plant microRNA in mice. Food Sci Nutr 2 380−388 2014. http://dx.doi.org/10.1002/fsn3.113

  • Liu WH Yeh SH Lu CC Yu SL Chen HY Lin CY Chen DS Chen PJ. MicroRNA-18a prevents estrogen receptoralpha expression promoting proliferation of hepatocellular carcinoma cells. Gastroenterology 136 683−693 2009. http://dx.doi.org/10.1053/j.gastro.2008.10.029

  • Liu DZ Tian Y Ander BP Xu H Stamova BS Zhan X Turner RJ Jickling G Sharp FR. Brain and blood microRNA expression profiling of ischemic stroke intracerebral hemorrhage and kainate seizures. J Cereb Blood Flow Metab 30 92-101 2010a. http://dx.doi.org/10.1038/jcbfm.2009.186

  • 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. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Invest 120 1298−309 2010b. http://dx.doi.org/10.1172/JCI39566

  • Liu M Zhi Q Wang W Zhang Q Fang T Ma Q. Up-regulation of miR-592 correlates with tumor progression and poor prognosis in patients with colorectal cancer. Biomed Pharmacother 69 214−220 2015. http://dx.doi.org/10.1016/j.biopha.2014.12.001

  • Long G Wang F Li H Yin Z Sandip C Lou Y Wang Y Chen C Wang DW. Circulating miR-30a miR-126 and let-7b as biomarker for ischemic stroke in humans. BMC Neurol 13 178 2013. http://dx.doi.org/10.1186/1471-2377-13-178

  • Lu J Getz G Miska EA Alvarez-Saavedra E Lamb J Peck D Sweet-Cordero A Ebert BL Mak RH Ferrando AA Downing JR Jacks T Horvitz HR Golub TR. MicroRNA expression profiles classify human cancers. Nature 435 834−838 2005. http://dx.doi.org/10.1038/nature03702

  • Lu J Guo S Ebert BL Zhang H Peng X Bosco J Pretz J Schlanger R Wang JY Mak RH Dombkowski DM Preffer FI Scadden DT Golub TR. MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Dev Cell 14 843−853 2008. http://dx.doi.org/10.1016/j.devcel.2008.03.012

  • Luo SS Ishibashi O Ishikawa G Ishikawa T Katayama A Mishima T Takizawa T Shigihara T Goto T Izumi A Ohkuchi A Matsubara S Takeshita TTakizawa T. Human villous trophoblasts express and secrete placenta specific microRNAs into maternal circulation via exosomes. Biol Reprod 81 717−729 2009. http://dx.doi.org/10.1095/biolreprod.108.075481

  • Luo H Zou J Dong Z Zeng Q Wu D Liu L. Up-regulated miR-17 promotes cell proliferation tumour growth and cell cycle progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma. Biochem J 442 311−321 2012. http://dx.doi.org/10.1042/BJ20111517

  • Ma R Jiang T Kang X. Circulating microRNAs in cancer: origin function and application. J Exp Clin Cancer Res 31 38 2012. http://dx.doi.org/10.1186/1756-9966-31-38

  • Mahn R Heukamp LC Rogenhofer S von Ruecker A Muller SC Ellinger J. Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology 77 1265.e9−16 2011. http://dx.doi.org/10.1016/j.urology.2011.01.020

  • Makeyev EV Zhang J Carrasco MA Maniatis T. Th e MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNAsplicing. Mol Cell 27 435−448 2007. http://dx.doi.org/10.1016/j.molcel.2007.07.015

  • Mitchell PS Parkin RK Kroh EM Fritz BR Wyman SK Pogosova-Agadjanyan EL Peterson A Noteboom J O’Briant KC Allen A Lin DW Urban N Drescher CW Knudsen BS Stirewalt DL Gentleman R Vessella RL Nelson PS Martin DB Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105 10513-10518 2008. http://dx.doi.org/10.1073/pnas.0804549105

  • Mogilyansky E Rigoutsos I. The miR-17/92 cluster: a comprehensive update on its genomics genetics functions and increasingly important and numerous roles in health and disease. Cell Death Diff er 20 1603−1614 2013. http://dx.doi.org/10.1038/cdd.2013.125

  • Mulcahy LA Pink RC Carter DR. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles 3 eCollection 2014. http://dx.doi.org/10.3402/jev.v3.24641

  • Murata K Furu M Yoshitomi H Ishikawa M Shibuya H Hashimoto M Imura Y Fujii T Ito H Mimori T Matsuda S. Comprehensive microRNA Analysis Identifies miR-24 and miR-125a-5p as Plasma Biomarkers for Rheumatoid Arthritis. PLoS One 8 e69118 2013. http://dx.doi.org/10.1371/journal.pone.0069118

  • Nagel R Clijsters L Agami R. The miRNA-192/194 cluster regulates the Period gene family and the circadian clock. FEBS J 276 5447-5455 2009. http://dx.doi.org/10.1111/j.1742-4658.2009.07229.x

  • Nielsen LB Wang C Sorensen K Bang-Berthelsen CH Hansen L Andersen ML Hougaard P Juul A Zhang CY Pociot F Mortensen HB. Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Exp Diabetes Res 2012 896362 2012. http://dx.doi.org/10.1155/2012/896362

  • Ohshima K Inoue K Fujiwara A Hatakeyama K Kanto K Watanabe Y Muramatsu K Fukuda Y Ogura S Yamaguchi K Mochizuki T. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 5 e13247 2010. http://dx.doi.org/10.1371/journal.pone.0013247

  • Pang J Xiong H Yang H Ou Y Xu Y Huang Q Lai L Chen S Zhang Z Cai Y Zheng Y. Circulating miR-34a levels correlate with age-related hearing loss in mice and humans. Exp Gerontol 76 58−67 2016. http://dx.doi.org/10.1016/j.exger.2016.01.009

  • Park NJ Zhou H Elashoff D Henson BS Kastratovic DA Abemayor E Wong DT. Salivary microRNA: discovery characterization and clinical utility for oral cancer detection. Clin Cancer Res 15 5473-5477 2009. http://dx.doi.org/10.1158/1078-0432.CCR-09-0736

  • Pedersen I David M. MicroRNAs in the immune response. Cytokine 43 391−394 2008. http://dx.doi.org/10.1016/j.cyto.2008.07.016

  • Persengiev S Kondova I Otting N Koeppen AH Bontrop RE. Genome-wide analysis of miRNA expression reveals a potential role for miR-144 in brain aging and spinocerebell arataxia pathogenesis. Neurobiol Aging 32 2316. e17−27 2011. http://dx.doi.org/10.1016/j.neurobiolaging.2010.03.014

  • Pigati L Yaddanapudi SC Iyengar R Kim DJ Hearn SA Danforth D Hastings ML Duelli DM. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One 5 e13515 2010. http://dx.doi.org/10.1371/journal.pone.0013515

  • Poliseno L Tuccoli A Mariani L Evangelista M Citti L Woods K Mercatanti A Hammond S Rainaldi G. MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108 3068-3071 2006. http://dx.doi.org/10.1182/blood-2006-01-012369

  • Poy MN Spranger M Stoffel M. microRNAs and the regulation of glucose and lipid metabolism. Diabetes Obes Metab 9 67−73 2007. http://dx.doi.org/10.1111/j.1463-1326.2007.00775.x

  • Pritchard CC Kroh E Wood B Arroyo JD Dougherty KJ Miyaji MM Tait JF Tewari M. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev Res (Phila) 5 492−497 2012. http://dx.doi.org/10.1158/1940-6207.CAPR-11-0370

  • Redis RS Calin S Yang Y You MJ Calin GA. Cell-to-cell miRNA transfer: from body homeostasis to therapy. Pharmacol Th er 136 169−174 2012. http://dx.doi.org/10.1016/j.pharmthera.2012.08.003

  • Reid G Kirschner MB van Zandwijk N. Circulating microRNAs: Association with disease and potential use as biomarkers. Crit Rev Oncol Hematol 80 193−208 2011. http://dx.doi.org/10.1016/j.critrevonc.2010.11.004

  • Reinhart BJ Slack FJ Basson M Pasquinelli AE Bettinger JC Rougvie AE Horvitz HR Ruvkun G. Th e 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403 901-906 2000. http://dx.doi.org/10.1038/35002607

  • Roese-Koerner B Stappert L Koch P Brustle O Borghese L. Pluripotent stem cell-derived somatic stem cells as tool to study the role of microRNAs in early human neural development. Curr Mol Med 13 707−722 2013. http://dx.doi.org/10.2174/1566524011313050003

  • Sarkar J Gou D Turaka P Viktorova E Ramchandran R Raj JU. MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration. Am J Physiol Lung Cell Mol Physiol 299 L861−871 2010. http://dx.doi.org/10.1152/ajplung.00201.2010

  • Sayed D Hong C Chen IY Lypowy J Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 100 416−424 2007. http://dx.doi.org/10.1161/01.RES.0000257913.42552.23

  • Shende VR Goldrick MM Ramani S Earnest DJ. Expression and Rhythmic Modulation of Circulating MicroRNAs Targeting the Clock Gene Bmal1 in Mice. PLoS One 6 e22586 2011. http://dx.doi.org/10.1371/journal.pone.0022586

  • Shi B Sepp-Lorenzino L Prisco M Linsley P deAngelis T Baserga R. Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem 282 32582−32590 2007. http://dx.doi.org/10.1074/jbc.M702806200

  • Shi XB Xue L Ma AH Tepper CG Gandour-Edwards R Kung HJ deVere White RW. Tumor suppressive miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells. Oncogene 32 4130−4138 2013. http://dx.doi.org/10.1038/onc.2012.425

  • Schratt GM Tuebing F Nigh EA Kane CG Sabatini ME Kiebler M Greenberg ME. A brain-specific microRNA regulates dendritic spine development. Nature 439 283-289 2006. http://dx.doi.org/10.1038/nature04367

  • Squadrito ML Baer C Burdet F Maderna C Gilfillan GD Lyle R Ibberson M De Palma M. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep 8 1432−4146 2014. http://dx.doi.org/10.1016/j.celrep.2014.07.035

  • Su YW Chen X Jiang ZZ Wang T Wang C Zhang Y Wen J Xue M Zhu D Zhang Y Su YJ Xing TY Zhang CY Zhang LY. A panel of serum microRNAs as specific biomarkers for diagnosis of compound- and herb-induced liver injury in rats. PLoS One 7 e37395 2012. http://dx.doi.org/10.1371/journal.pone.0037395

  • Sun D Yu F Ma Y Zhao R Chen X Zhu J Zhang CY Chen J Zhang J. MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1). J Biol Chem 288 9508−9518 2013. http://dx.doi.org/10.1074/jbc.M112.367763

  • Sun X Yang Z Zhang Y He J Wang F Su P Han J Song Z Fei Y. Prognostic implications of tissue and serum levels of microRNA-128 in human prostate cancer. Int J Clin Exp Pathol 8 8394−8401 2015.

  • Silvestre JS Mallat Z Tedgui A Levy BI. Post-ischaemic neovascularization and inflammation. Cardiovasc Res 78 242-249. 2008. http://dx.doi.org/10.1093/cvr/cvn027.

  • Szafranski K Abraham KJ Mekhail K. Non-coding RNA in neural function disease and aging. Front Genet 6 87 eCollection 2015. http://dx.doi.org/10.3389/fgene.2015.00087

  • Tang P Xiong Q Ge W Zhang L. Th e role of microRNAs in osteoclasts and osteoporosis. RNA Biol 11 1355-1363 2014. http://dx.doi.org/10.1080/15476286.2014.996462

  • Tang R Yang C Ma X Wang Y Luo D Huang C Xu Z Liu P Yang L. MiR-let-7a inhibits cell proliferation migration and invasion by down-regulating PKM2 in gastric cancer. Oncotarget 7 5972-5984. 2016. http://dx.doi.org/10.18632/oncotarget.6821

  • Thomson JM Newman M Parker JS Morin-Kensicki EM Wright T Hammond SM. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev 20 2202-2207 2006. http://dx.doi.org/10.1101/gad.1444406

  • Tian Y Liu Y Wang T Zhou N Kong J Chen L Snitow M Morley M Li D Petrenko N Zhou S Lu M Gao E Koch WJ Stewart KM Morrisey EE. A microRNA-hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice. Sci Transl Med 7 279ra38 2015. http://dx.doi.org/10.1126/scitranslmed.3010841

  • Title AC Denzler R Stoffel M. Uptake and Function Studies of Maternal Milk-derived MicroRNAs. J Biol Chem 290 23680−23691 2015. http://dx.doi.org/10.1074/jbc.M115.676734

  • Toiyama Y Takahashi M Hur K Nagasaka T Tanaka K Inoue Y Kusunoki M Boland CR Goel A. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst 105 849−859 2013. http://dx.doi.org/10.1093/jnci/djt101

  • Turchinovich A Weiz L Langheinz A Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res 39 7223−7233 2011. http://dx.doi.org/10.1093/nar/gkr254

  • Valeri N Gasparini P Braconi C Paone A Lovat F Fabbri M Sumani KM Alder H Amadori D Patel T Nuovo GJ Fishel R Croce CM. MicroRNA-21 induces resistance to 5-fl uorouracil by down-regulating human DNA MutS homolog 2 (hMSH2). Proc Natl Acad Sci U S A 107 21098−21103 2010. http://dx.doi.org/10.1073/pnas.1015541107

  • van Rooij E Sutherland LB Liu N Williams AH McAnally J Gerard RD Richardson JA Olson EN. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A 103 18255-18260 2006. http://dx.doi.org/10.1073/pnas.0608791103

  • van Rooij E Sutherland LB Qi X Richardson JA Hill J Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316 575−579 2007. http://dx.doi.org/10.1126/science.1139089

  • van Rooij E Olson EN. Searching for miR-acles in cardiac fibrosis. Circ Res 104 138−140 2009. http://dx.doi.org/10.1161/CIRCRESAHA.108.192492

  • Vickers KC Palmisano BT Shoucri BM Shamburek RD Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins: Nat Cell Biol 13 423−433 2011. http://dx.doi.org/10.1038/ncb2210

  • Wang K Zhang S Marzolf B Troisch P Brightman A Hu Z Hood LE Galas DJ. Circulating microRNAs potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A 106 4402-4407 2009a. http://dx.doi.org/10.1073/pnas.0813371106

  • Wang CJ Zhou ZG Wang L Yang L Zhou B Gu J Chen HY Sun XF. Clinicopathological signifi cance of microRNA-31 -143 and -145 expression in colorectal cancer. Dis Markers 26 27-34 2009b. http://dx.doi.org/10.1155/2009/921907

  • Wang K Zhang S Weber J Baxter D Galas DJ. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res 38 7248-7259 2010a. http://dx.doi.org/10.1093/nar/gkq601

  • Wang CJ Stratmann J Zhou ZG Sun XF. Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage and affects cell migration and invasion in HCT-116 colon cancer cells. BMC Cancer 10 616 2010b. http://dx.doi.org/10.1186/1471-2407-10-616

  • Wang B Zhang Q. Th e expression and clinical significance of circulating microRNA-21 in serum of five solid tumors. J Cancer Res Clin Oncol 138 1659-1666 2012. http://dx.doi.org/10.1007/s00432-012-1244-9

  • Wang Q Huang Z Ni S Xiao X Xu Q Wang L Huang D Tan C Scheng W Du X. Plasma miR-601 and miR-760 Are Novel Biomarkers for the Early Detection of Colorectal Cancer. PLoS One 7 e44398 2012a. http://dx.doi.org/10.1371/journal.pone.0044398

  • Wang H Peng W Ouyang X Li W Dai Y. Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus. Transl Res 160 198-206 2012b. http://dx.doi.org/10.1016/j.trsl.2012.04.002

  • Wang YC Li Y Wang XY Zhang D Zhang H Wu Q He YQ Wang JY Zhang L Xia H Yan J Li X Ying H. Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity. Diabetologia 56 2275-2285 2013. http://dx.doi.org/10.1007/s00125-013-2996-8

  • Wang F Long G Zhao C Li H Chaugai S Wang Y Chen C Wang DW. Atherosclerosis-Related Circulating miRNAs as Novel and Sensitive Predictors for Acute Myocardial Infarction. PLoS One 9 e105734 2014. http://dx.doi.org/10.1371/journal.pone.0105734

  • Welch C Chen Y Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 26 5017−5022 2007. http://dx.doi.org/10.1038/sj.onc.1210293

  • Wightman B Ha I Ruvkun G. Posttranscriptional regulation of the heterochronic gene Lin-14 by Lin-4 mediates temporal pattern-formation in C.elegans. Cell 75 855-862 1993. http://dx.doi.org/10.1016/0092-8674(93)90530-4

  • Witwer KW Hirschi KD. Transfer and functional consequences of dietary microRNAs in vertebrates: concepts in search of corroboration: negative results challenge the hypothesis that dietary xenomiRs cross the gut and regulate genes in ingesting vertebrates but important questions persist. Bioessays 36 394−406 2014. http://dx.doi.org/10.1002/bies.201300150

  • Wu CW Dong YJ Liang QY He XQ Ng SS Chan FK Sung JJ Yu J. MicroRNA-18a attenuates DNA damage repair through suppressing the expression of ataxia telangiectasia mutated in colorectal cancer. PLoS One 8 e57036 2013. http://dx.doi.org/10.1371/journal.pone.0057036

  • Wulfken LM Moritz R Ohlmann C Holdenrieder S Jung V Becker F Herrmann E Walgenbach-Brunagel G von Ruecker A Muller SC Ellinger J. MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One 6 e25787 2011. http://dx.doi.org/10.1371/journal.pone.0025787

  • Xiong J Yu D Wei N Fu H Cai T Huang Y Wu C Zheng X Du Q Lin D Liang Z. An estrogen receptor alpha suppressor microRNA-22 is downregulated in estrogen receptor alpha-positive human breast cancer cell lines and clinical samples. FEBS J 277 1684−1694 2010. http://dx.doi.org/10.1111/j.1742-4658.2010.07594.x

  • Xiong B Cheng Y Ma L Zhang C. MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorectal cancer cells. Int J Oncol 42 219−228 2013. http://dxdoi/10.3892/ijo.2012.1707.

  • Xu RS Wu XD Zhang SQ Li CF Yang L Li DD Zhang BG Zhang Y Jin JP Zhang B. Th e tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer. Int J Oncol 42 676−682 2013. http://dxdoi/10.3892/ijo.2012.1746

  • Xu L Li M Wang M Yan D Feng G An G. The expression of microRNA-375 in plasma and tissue is matched in human colorectal cancer. BMC Cancer 14 714 2014. http://dx.doi.org/10.1186/1471-2407-14-714

  • Yamada H Itoh M Hiratsuka I Hashimoto S. Circulating microRNAs in autoimmune thyroid diseases. Clin Endocrinol (Oxf) 81 276−281 2014. http://dx.doi.org/10.1111/cen.12432

  • Yang B Lin H Xiao J Lu Y Luo X Li B Zhang Y Xu C Bai Y Wang H Chen G Wang Z. Th e muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 13 486-491 2007. http://dx.doi.org/10.1038/nm1569

  • Yang Z Chen H Si H Li X Ding X Sheng Q Chen P Zhang H. Serum miR-23a a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes. Acta Diabetol 51 823−831 2014. http://dx.doi.org/10.1007/s00592-014-017-8

  • Yang Y Chang S Zhao Z Hou NI He K Wang X Gao L Wang L Cai D Guo BO Tong D Song T Huang C. MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3. Oncol Lett 10 3779-3784 2015. http://dx.doi.org/10.3892/ol.2015.3745

  • Ye W Lv Q Wong C-KA Hu S Fu C Hua Z Cai G Li G Yang BB Zhang Y. The Effect of Central Loops in miRNA:MRE Duplexes on the Efficiency of miRNA-Mediated Gene Regulation. PLoS One 3 e1719 2008. http://dx.doi.org/10.1371/journal.pone.0001719

  • Zampetaki A Kiechl S Drozdov I Willeit P Mayr U Prokopi M Mayr A Weger S Oberhollenzer F Bonora E Shah A Willeit J Mayr M. Plasma microRNA profi ling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 107 810-817 2010. http://dx.doi.org/10.1161/CIRCRESAHA.110.226357

  • Zampetaki A Willeit P Drozdov I Kiechl S Mayr M. Profiling of circulating microRNAs: from single biomarkers to re-wired networks. Cardiovasc Res 93 555−562 2012. http://dx.doi.org/10.1093/cvr/cvr266

  • Zeng W Tu Y Zhu Y Wang Z Li C Lao L Wu G. Predictive power of circulating miRNAs in detecting colorectal cancer. Tumour Biol 36 2559−2567 2015. http://dx.doi.org/10.1007/s13277-014-2872-2

  • Zhang B Wang Q Pan X. MicroRNA and Th eir Regulatory Roles in Animals and Plants. J Cell Physiol 210 279-289 2007a. http://dx.doi.org/10.1002/jcp.20869

  • Zhang B Pan X Cobb GP Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol 302 1-12 2007b. http://dx.doi.org/10.1016/j.ydbio.2006.08.028

  • Zhang C. MicroRNAs: role in cardiovascular biology and disease. Clin Sci (Lond) 114 699-706 2008. http://dx.doi.org/10.1042/CS20070211

  • Zhang Z Li Z Gao C Chen P Chen J Liu W Xiao S Lu H. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest 88 1358-1366 2008. http://dx.doi.org/10.1038/labinvest.2008.94

  • Zhang L Hou D Chen X Li D Zhu L Zhang Y Li J Bian Z Liang X Cai X Yin Y Wang C Zhang T Zhu D Zhang D Xu J Chen Q Ba Y Liu J Wang Q Chen J Wang J Wang M Zhang Q Zhang J Zen K Zhang CY. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res 22 107-126 2012. http://dx.doi.org/10.1038/cr.2011.174

  • Zheng L Xu CC Chen WD Shen WL Ruan CC Zhu LM Zhu DL Gao PJ. MicroRNA-155 regulates angiotensin II type 1 receptor expression and phenotypic differentiation in vascular adventitial fibroblasts. Biochem Biophys Res Commun 400 483−488 2010. http://dx.doi.org/10.1016/j.bbrc.2010.08.067

  • Zong L Zhu Y Liang R Zhao HB. Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellulargenetic communication. Sci Rep 6 19884 2016. http://dx.doi.org/10.1038/srep19884

  • Zuckerman JE Davis ME. Clinical experiences with systemically administered siRNA-based therapeutics in cancer. Nat Rev Drug Discov 14 843−856 2015. http://dx.doi.org/10.1038/nrd4685

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