A brief primer on microRNAs and their roles in angiogenesis

Journal of Angiogenesis Research

Sudarshan Anand¹ 

[1] Moores UCSD Cancer Center, 3855 Health Sciences Drive #0803, La Jolla, CA, 92093, USA

关键词: Ocular angiogenesis;    NOTCH;    p120RasGAP;    miR-132;    miR-126;    microRNA networks;    Angiogenesis;   

Others  :  801770
DOI  :  10.1186/2045-824X-5-2

 received in 2012-11-15, accepted in 2013-01-11,  发布年份 2013

【 摘 要 】

Development of the vasculature is a complex, dynamic process orchestrated by a balance of pro and anti-angiogenic signaling pathways. The same signaling pathways are mis-regulated and exploited during pathological angiogenesis in cancer, inflammation and cardiovascular diseases and contribute to disease progression. In the last decade, small non-coding RNA molecules termed microRNAs (miRs) have emerged as key regulators of several cellular processes including angiogenesis. It is becoming clear that miRs function in complex networks and regulate gene expression both at the mRNA and protein levels thereby altering cellular signaling responses to specific stimuli. In the vasculature, miRs can function either in a pro-angiogenic manner and potentiate angiogenesis or act as anti-angiogenic miRs by enhancing cell death and decreasing endothelial proliferation. This review aims to provide an update on how microRNAs regulate gene expression and illustrate miR function in the vasculature with a discussion of potential applications of miRs as anti-angiogenic therapeutics.

【 授权许可】

   
2013 Anand; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E, Scott F, Martinborough E, Peach R, Oldstone MB, Rosen H: Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011, 146(6):980-991.
• [2]Ding L, Saunders TL, Enikolopov G, Morrison SJ: Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 2012, 481(7382):457-462.
• [3]Tran K-V, Gealekman O, Frontini A, Zingaretti Maria C, Morroni M, Giordano A, Smorlesi A, Perugini J, De Matteis R, Sbarbati A, et al.: The vascular endothelium of the adipose tissue gives rise to both white and brown Fat cells. Cell Metabol 2012, 15(2):222-229.
• [4]Chung AS, Ferrara N: Developmental and pathological angiogenesis. Annual Rev Cell Develop Biol 2011, 27(1):563-584.
• [5]Bonauer A, Boon RA, Dimmeler S: Vascular microRNAs. Curr Drug Targets 2010, 11(8):943-949.
• [6]Hartmann D, Thum T: MicroRNAs and vascular (dys)function. Vasc Pharmacol 2011, 55(4):92-105.
• [7]Small EM, Olson EN: Pervasive roles of microRNAs in cardiovascular biology. Nature 2011, 469(7330):336-342.
• [8]Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009, 136(2):215-233.
• [9]Kozomara A, Griffiths-Jones S: miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011, 39(suppl 1):D152-D157.
• [10]Treiber T, Treiber N, Meister G: Regulation of microRNA biogenesis and function. Thromb Haemost 2012, 107(4):605-610.
• [11]Yang J-S, Lai Eric C: Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Molecular cell 2011, 43(6):892-903.
• [12]Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S: Role of dicer and drosha for endothelial microRNA expression and angiogenesis. Circ Res 2007, 101(1):59-68.
• [13]Zhang B, Pan X, Cobb GP, Anderson TA: Plant microRNA: a small regulatory molecule with big impact. Dev Biol 2006, 289(1):3-16.
• [14]Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP: The impact of microRNAs on protein output. Nature 2008, 455(7209):64-71.
• [15]Guo H, Ingolia NT, Weissman JS, Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010, 466(7308):835-840.
• [16]Huntzinger E, Izaurralde E: Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 2011, 12(2):99-110.
• [17]Ebert Margaret S, Sharp Phillip A: Roles for MicroRNAs in conferring robustness to biological processes. Cell 2012, 149(3):515-524.
• [18]Li X, Cassidy JJ, Reinke CA, Fischboeck S, Carthew RW: A microRNA imparts robustness against environmental fluctuation during development. Cell 2009, 137(2):273-282.
• [19]Sokol NS, Ambros V: Mesodermally expressed drosophila microRNA-1 is regulated by twist and is required in muscles during larval growth. Genes Dev 2005, 19(19):2343-2354.
• [20]Osella M, Bosia C, Corá D, Caselle M: The role of incoherent MicroRNA-mediated feedforward loops in noise buffering. PLoS Comput Biol 2011, 7(3):e1001101.
• [21]Yang WJ, Yang DD, Na S, Sandusky GE, Zhang Q, Zhao G: Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem 2005, 280(10):9330-9335.
• [22]Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF: MicroRNAs regulate brain morphogenesis in zebrafish. Science 2005, 308(5723):833-838.
• [23]Suarez Y, Fernandez-Hernando C, Yu J, Gerber SA, Harrison KD, Pober JS, Iruela-Arispe ML, Merkenschlager M, Sessa WC: Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci U S A 2008, 105(37):14082-14087.
• [24]Albinsson S, Skoura A, Yu J, DiLorenzo A, Fernandez-Hernando C, Offermanns S, Miano JM, Sessa WC: Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function. PLoS One 2011, 6(4):e18869.
• [25]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 2006, 108(9):3068-3071.
• [26]Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D: miR-126 regulates angiogenic signaling and vascular integrity. Develop cell 2008, 15(2):272-284.
• [27]Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN: The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Develop cell 2008, 15(2):261-271.
• [28]Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND: MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature 2010, 464(7292):1196-1200.
• [29]Png KJ, Halberg N, Yoshida M, Tavazoie SF: A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 2012, 481(7380):190-194.
• [30]Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, et al.: MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 2009, 324(5935):1710-1713.
• [31]Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Y, Urbich C, Hofmann W-K, Zeiher AM, Dimmeler S: Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood 2010, 115(23):4944-4950.
• [32]Anand S, Cheresh DA: Emerging role of micro-RNAs in the regulation of angiogenesis. Genes & cancer 2011, 2(12):1134-1138.
• [33]Landskroner-Eiger S, Moneke I, Sessa WC: MiRNAs as modulators of angiogenesis. Cold Spring Harbor perspect med 2012. Advance Online Publication
• [34]Otsuka M, Zheng M, Hayashi M, Lee JD, Yoshino O, Lin S, Han J: Impaired microRNA processing causes corpus luteum insufficiency and infertility in mice. J Clin Invest 2008, 118(5):1944-1954.
• [35]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 U S A 2008, 105(5):1516-1521.
• [36]Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Lapinski PE, et al.: MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat med 2010, 16(8):909-914.
• [37]Jin W, Reddy MA, Chen Z, Putta S, Lanting L, Kato M, Park JT, Chandra M, Wang C, Tangirala RK, et al.: Small RNA sequencing reveals MicroRNAs that modulate angiotensin II effects in vascular smooth muscle cells. J Biol Chem 2012, 287(19):15672-15683.
• [38]Fasanaro P, D’Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC, Martelli F: MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 2008, 283(23):15878-15883.
• [39]Pulkkinen K, Malm T, Turunen M, Koistinaho J, Yla-Herttuala S: Hypoxia induces microRNA miR-210 in vitro and in vivo ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210. FEBS Lett 2008, 582(16):2397-2401.
• [40]Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, Weissleder R, Breakefield XO, Krichevsky AM: miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer cell 2008, 14(5):382-393.
• [41]Ghosh G, Subramanian IV, Adhikari N, Zhang X, Joshi HP, Basi D, Chandrashekhar YS, Hall JL, Roy S, Zeng Y, et al.: Hypoxia-induced microRNA-424 expression in human endothelial cells regulates HIF-alpha isoforms and promotes angiogenesis. J Clin Invest 2010, 120(11):4141-4154.
• [42]Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D: miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 2009, 460(7256):705-710.
• [43]Leeper NJ, Raiesdana A, Kojima Y, Chun HJ, Azuma J, Maegdefessel L, Kundu RK, Quertermous T, Tsao PS, Spin JM: MicroRNA-26a is a novel regulator of vascular smooth muscle cell function. J Cell Physiol 2011, 226(4):1035-1043.
• [44]Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne RS, Gotch F, Boshoff C: miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat cell biol 2010, 12(5):513-519.
• [45]Mulik S, Xu J, Reddy PBJ, Rajasagi NK, Gimenez F, Sharma S, Lu PY, Rouse BT: Role of miR-132 in angiogenesis after ocular infection with herpes simplex virus. Am J Pathol 2012, 181(2):525-534.
• [46]Katare R, Riu F, Mitchell K, Gubernator M, Campagnolo P, Cui Y, Fortunato O, Avolio E, Cesselli D, Beltrami AP, et al.: Transplantation of human pericyte progenitor cells improves the repair of infarcted heart through activation of an angiogenic program involving micro-RNA-132/novelty and significance. Circ Res 2011, 109(8):894-906.
• [47]Boucher JM, Peterson SM, Urs S, Zhang C, Liaw L: The miR-143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells. J Biol Chem 2011, 286(32):28312-28321.
• [48]Dentelli P, Rosso A, Orso F, Olgasi C, Taverna D, Brizzi MF: microRNA-222 controls neovascularization by regulating signal transducer and activator of transcription 5A expression. Arterioscler Thromb Vasc Biol 2010, 30(8):1562-1568.
• [49]Wayman GA, Davare M, Ando H, Fortin D, Varlamova O, Cheng HY, Marks D, Obrietan K, Soderling TR, Goodman RH, et al.: An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proc Natl Acad Sci U S A 2008, 105(26):9093-9098.
• [50]Harris TA, Yamakuchi M, Kondo M, Oettgen P, Lowenstein CJ: Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arterioscler Thromb Vasc Biol 2010, 30(10):1990-1997.
• [51]Chen K, Rajewsky N: Deep conservation of MicroRNA-target relationships and 3’UTR motifs in vertebrates, flies, and nematodes. Cold Spring Harbor Symposia Quantitative Biol 2006, 71:149-156.
• [52]Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, et al.: The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 2011, 39(suppl 1):D561-D568.
• [53]MicroRNA clinical trials from Clinical Trials.govhttp://clinicaltrials.gov/ct2/results?term=MICRORNA&Search=Search webcite
• [54]Reesink HWJHLA, Zeuzem S, Lawitz E, Rodriguez-Torres M, Patel K, Chen A, Davis C, King B, Levin A, Hodges MR: Final Results - Randomized, Double-blind, Placebo-controlled Safety, Anti-viral Proof-of-Concept Study of Miravirsen, an Oligonucleotide Targeting miR-122, in Treatment-naïve Patients with Genotype1 (GT1) chronic HCV infection. In: 47th Annual Meeting of the European Association for the study of the liver: April 18-22. J Hepatol 2012, 56(suppl2):s26.
• [55]Garzon R, Marcucci G, Croce CM: Targeting microRNAs in cancer: rationale, strategies and challenges. Nat rev Drug discov 2010, 9(10):775-789.
• [56]Trang P, Weidhaas JB, Slack FJ: MicroRNAs as potential cancer therapeutics. Oncogene 2008, 27(Suppl 2):S52-S57.
• [57]Lima Walt F, Prakash Thazha P, Murray Heather M, Kinberger Garth A, Li W, Chappell Alfred E, Li Cheryl S, Murray Susan F, Gaus H, Seth Punit P, et al.: Single-stranded siRNAs activate RNAi in animals. Cell 2012, 150(5):883-894.
• [58]Yu D, Pendergraff H, Liu J, Kordasiewicz HB, Cleveland Don W, Swayze Eric E, Lima Walt F, Crooke Stanley T, Prakash Thazha P, Corey David R: Single-stranded RNAs Use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell 2012, 150(5):895-908.
• [59]Yancopoulos GD: Clinical application of therapies targeting VEGF. Cell 2010, 143(1):13-16.
• [60]Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR: Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004, 351(27):2805-2816.
• [61]Kurihara T, Westenskow PD, Bravo S, Aguilar E, Friedlander M: Targeted deletion of vegfa in adult mice induces vision loss. J Clin Invest 2012, 122(11):4213-4217.