MicroRNAs in pulmonary arterial hypertension

American Journal of Respiratory Cell and Molecular Biology

Volumn 52, Issue 2, 2015, Pages 139-151

  Zhou, Guofei ^a   Chen, Tianji ^a   Usha Raj, J ^a,b  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b CHILDREN'S MEMORIAL HOSPITAL   (United States)

Author keywords

Fibroblasts; MicroRNA; Pulmonary arterial hypertension; Pulmonary artery endothelial cells; Pulmonary artery smooth muscle cell

Indexed keywords

MICRORNA; MICRORNA 124; MICRORNA 143; MICRORNA 145; MICRORNA 204; MICRORNA 21; MICRORNA 210; MICRORNA 27A; MICRORNA 424; MICRORNA 503; UNCLASSIFIED DRUG;

ENDOTHELIUM CELL; FIBROBLAST; GENE CLUSTER; GENE EXPRESSION; HUMAN; NONHUMAN; PATHOGENESIS; PHENOTYPE; PULMONARY ARTERY; PULMONARY ARTERY SMOOTH MUSCLE CELL; PULMONARY HYPERTENSION; REVIEW; SMOOTH MUSCLE FIBER; ANIMAL; GENETICS; METABOLISM; SMOOTH MUSCLE CELL;

ANIMALS; ENDOTHELIAL CELLS; FIBROBLASTS; HUMANS; HYPERTENSION, PULMONARY; MICRORNAS; MYOCYTES, SMOOTH MUSCLE; PULMONARY ARTERY;

EID: 84922236180     PISSN: 10441549     EISSN: 15354989     Source Type: Journal    
DOI: 10.1165/rcmb.2014-0166TR     Document Type: Review

References (131)

1. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004;351:1425-1436. (see comment).
2. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, et al .; ACCF/AHA. Accf/aha 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association. Circulation 2009;119:2250-2294.
3. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013;62(Suppl):D34-D41.
4. Lee R, Feinbaum R, Ambros V. A short history of a short rna. Cell 2004; 116(Suppl):S89-S92, 1 p. following S96.
5. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008;9:102-114.
6. Potus F, Graydon C, Provencher S, Bonnet S. Vascular remodeling process in pulmonary arterial hypertension, with focus on miR-204 and miR-126 (2013 Grover Conference series). Pulm Circ 2014;4:175-184.
7. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009;11:228-234.
8. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013; 12:847-865.
9. Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature 2007;448:83-86.
10. Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 2007; 130:89-100.
11. Ladewig E, Okamura K, Flynt AS, Westholm JO, Lai EC. Discovery of hundreds of mirtrons in mouse and human small RNA data. Genome Res 2012;22:1634-1645.
12. Niwa R, Slack FJ. The evolution of animal microRNA function. Curr Opin Genet Dev 2007;17:145-150.
13. Inui M, Martello G, Piccolo S. MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 2010;11:252-263.
14. Lee C-T, Risom T, Strauss WM. Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny. DNA Cell Biol 2007;26:209-218.
15. miRBase: the microRNA database [accessed 2014 Mar 18]. Available from: http://www.mirbase.org/index.shtml
16. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 2008;132:875-886.
17. Hackl M, Brunner S, Fortschegger K, Schreiner C, Micutkova L, Mück C, Laschober GT, Lepperdinger G, Sampson N, Berger P, et al. miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging. Aging Cell 2010;9:291-296.
18. Wu T, Wieland A, Araki K, Davis CW, Ye L, Hale JS, Ahmed R. Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation. Proc Natl Acad Sci USA 2012; 109:9965-9970.
19. Mujahid S, Logvinenko T, Volpe MV, Nielsen HC. miRNA regulated pathways in late stage murine lung development. BMC Dev Biol 2013;13:13.
20. Nallamshetty S, Chan SY, Loscalzo J. Hypoxia: a master regulator of microRNA biogenesis and activity. Free Radic Biol Med 2013;64:20-30.
21. Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 2007;129:1401-1414.
22. Sood P, Krek A, Zavolan M, Macino G, Rajewsky N. Cell-type-specific signatures of microRNAs on target mRNA expression. Proc Natl Acad Sci USA 2006;103:2746-2751.
23. Shkumatava A, Stark A, Sive H, Bartel DP. Coherent but overlapping expression of microRNAs and their targets during vertebrate development. Genes Dev 2009;23:466-481.
24. Liu H, Kohane IS. Tissue and process specific microRNA-mRNA co-expression in mammalian development and malignancy. PLoS One 2009;4:e5436.
25. Courboulin A, Paulin R, Giguère NJ, Saksouk N, Perreault T, Meloche J, Paquet ER, Biardel S, Provencher S, Côté J, et al. Role for miR-204 in human pulmonary arterial hypertension. J Exp Med 2011;208:535-548.
26. Rhodes CJ, Wharton J, Boon RA, Roexe T, Tsang H, Wojciak-Stothard B, Chakrabarti A, Howard LS, Gibbs JSR, Lawrie A, et al. Reduced microRNA-150 is associated with poor survival in pulmonary arterial hypertension. Am J Respir Crit Care Med 2013;187:294-302.
27. Pullamsetti SS, Doebele C, Fischer A, Savai R, Kojonazarov B, Dahal BK, Ghofrani HA, Weissmann N, Grimminger F, Bonauer A, et al. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am J Respir Crit Care Med 2012;185:409-419.
28. Chen T, Zhou G, Zhou Q, Ibe JCF, Comhair SA, Erzurum SC, Raj JU. Mir-17∼92 regulates differentiation of pulmonary arterial smooth muscle cells via a tgf-beta dependent pathway [abstract]. 2012: A2613, 10.1164/ajrccm-conference.2012.185.1-MeetingAbstracts.A2613.
29. Chen T, Zhou G, Zhou Q, Raj JU. Microrna-17∼92 regulates differentiation of pulmonary arterial smooth muscle cells via a pdlim5/tgf-beta/smad pathway. 2013: A2101, 10.1164/ajrccmconference.2013.187.1-MeetingAbstracts.A2101.
30. Caruso P, MacLean MR, Khanin R, McClure J, Soon E, Southgate M, MacDonald RA, Greig JA, Robertson KE, Masson R, et al. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler Thromb Vasc Biol 2010;30:716-723.
31. Drake KM, Zygmunt D, Mavrakis L, Harbor P, Wang L, Comhair SA, Erzurum SC, Aldred MA. Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8. Am J Respir Crit Care Med 2011;184:1400-1408.
32. Caruso P, Dempsie Y, Stevens HC, McDonald RA, Long L, Lu R, White K, Mair KM, McClure JD, Southwood M, et al. A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples. Circ Res 2012;111:290-300.
33. Joshi SR, McLendon JM, Comer BS, Gerthoffer WT. MicroRNAs-control of essential genes: Implications for pulmonary vascular disease. Pulm Circ 2011;1:357-364.
34. Sessa R, Hata A. Role of microRNAs in lung development and pulmonary diseases. Pulm Circ 2013;3:315-328.
35. Parikh VN, Jin RC, Rabello S, Gulbahce N, White K, Hale A, Cottrill KA, Shaik RS, Waxman AB, Zhang YY, et al. MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation 2012;125:1520-1532.
36. Brock M, Samillan VJ, Trenkmann M, Schwarzwald C, Ulrich S, Gay RE, Gassmann M, Ostergaard L, Gay S, Speich R, et al. AntagomiR directed against miR-20a restores functional BMPR2 signalling and prevents vascular remodelling in hypoxia-induced pulmonary hypertension. Eur Heart J (In press)
37. Yang S, Banerjee S, Freitas Ad, Cui H, Xie N, Abraham E, Liu G. miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 2012;302:L521-L529.
38. Bockmeyer CL, Maegel L, Janciauskiene S, Rische J, Lehmann U, Maus UA, Nickel N, Haverich A, Hoeper MM, Golpon HA, et al. Plexiform vasculopathy of severe pulmonary arterial hypertension and microrna expression. J Heart Lung Transplant 2012;31:764-772.
39. van Rooij E. The art of microRNA research. Circ Res 2011;108: 219-234.
40. Kang K, Zhang X, Liu H, Wang Z, Zhong J, Huang Z, Peng X, Zeng Y, Wang Y, Yang Y, et al. A novel real-time PCR assay of microRNAs using S-Poly(T), a specific oligo(dT) reverse transcription primer with excellent sensitivity and specificity. PLoS One 2012;7: e48536.
41. Tanzer A, Stadler PF. Molecular evolution of a microRNA cluster. J Mol Biol 2004;339:327-335.
42. Bonauer A, Dimmeler S. The microRNA-17-92 cluster: still a miRacle? Cell Cycle 2009;8:3866-3873.
43. 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 2010;299:L861-L871.
44. Kang K, Peng X, Zhang X, Wang Y, Zhang L, Gao L, Weng T, Zhang H, Ramchandran R, Raj JU, et al. MicroRNA-124 suppresses the transactivation of nuclear factor of activated T cells by targeting multiple genes and inhibits the proliferation of pulmonary artery smooth muscle cells. J Biol Chem 2013;288:25414-25427.
45. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee T-H, Miano JM, Ivey KN, Srivastava D. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 2009;460: 705-710.
46. Parmacek MS. MicroRNA-modulated targeting of vascular smooth muscle cells. J Clin Invest 2009;119:2526-2528.
47. Iio A, Nakagawa Y, Hirata I, Naoe T, Akao Y. Identi fication of noncoding RNAs embracing microRNA-143/145 cluster. Mol Cancer 2010;9:136.
48. Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MVG, Peterson KL, Indolfi C, Catalucci D, Chen J, et al. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ 2009;16:1590-1598.
49. Cheng Y, Liu X, Yang J, Lin Y, Xu D-Z, Lu Q, Deitch EA, Huo Y, Delphin ES, Zhang C. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res 2009;105:158-166.
50. Boettger T, Beetz N, Kostin S, Schneider J, Krüger M, Hein L, Braun T. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest 2009;119:2634-2647.
51. Davis-Dusenbery BN, Chan MC, Reno KE, Weisman AS, Layne MD, Lagna G, Hata A. Down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4. J Biol Chem 2011;286:28097-28110.
52. Wang FE, Zhang C, Maminishkis A, Dong L, Zhi C, Li R, Zhao J, Majerciak V, Gaur AB, Chen S, et al. MicroRNA-204/211 alters epithelial physiology. FASEB J 2010;24:1552-1571.
53. Lee C, Mitsialis SA, Aslam M, Vitali SH, Vergadi E, Konstantinou G, Sdrimas K, Fernandez-Gonzalez A, Kourembanas S. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation 2012;126: 2601-2611.
54. Chan SY, Loscalzo J. MicroRNA-210: a unique and pleiotropic hypoxamir. Cell Cycle 2010;9:1072-1083.
55. Gou D, Ramchandran R, Peng X, Yao L, Kang K, Sarkar J, Wang Z, Zhou G, Raj JU. miR-210 has an antiapoptotic effect in pulmonary artery smooth muscle cells during hypoxia. Am J Physiol Lung Cell Mol Physiol 2012;303:L682-L691.
56. Tréguer K, Heinrich E-M, Ohtani K, Bonauer A, Dimmeler S. Role of the microRNA-17-92 cluster in the endothelial differentiation of stem cells. J Vasc Res 2012;49:447-460.
57. Suárez Y, Fernández-Hernando C, Yu J, Gerber SA, Harrison KD, Pober JS, Iruela-Arispe ML, Merkenschlager M, Sessa WC. Dicerdependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci USA 2008;105:14082-14087.
58. Li W, Dunmore BJ, Morrell NW. Bone morphogenetic protein type II receptor mutations causing protein misfolding in heritable pulmonary arterial hypertension. Proc Am Thorac Soc 2010;7:395-398.
59. Brock M, Trenkmann M, Gay RE, Michel BA, Gay S, Fischler M, Ulrich S, Speich R, Huber LC. Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ Res 2009;104:1184-1191.
60. White K, Dempsie Y, Caruso P, Wallace E, McDonald RA, Stevens H, Hatley ME, Van Rooij E, Morrell NW, MacLean MR, et al. Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/programmed cell death 4/caspase-3 axis. Hypertension 2014;64: 185-194.
61. Kang B-Y, Park KK, Green DE, Bijli KM, Searles CD, Sutliff RL, Hart CM. Hypoxia mediates mutual repression between microRNA-27a and PPARg in the pulmonary vasculature. PLoS One 2013;8:e79503.
62. Chandra SM, Razavi H, Kim J, Agrawal R, Kundu RK, de Jesus Perez V, Zamanian RT, Quertermous T, Chun HJ. Disruption of the apelin-APJ system worsens hypoxia-induced pulmonary hypertension. Arterioscler Thromb Vasc Biol 2011;31:814-820.
63. Kim J, Kang Y, Kojima Y, Lighthouse JK, Hu X, Aldred MA, McLean DL, Park H, Comhair SA, Greif DM, et al. An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension. Nat Med 2013;19:74-82.
64. Tu L, Dewachter L, Gore B, Fadel E, Dartevelle P, Simonneau G, Humbert M, Eddahibi S, Guignabert C. Autocrine fibroblast growth factor-2 signaling contributes to altered endothelial phenotype in pulmonary hypertension. Am J Respir Cell Mol Biol 2011;45: 311-322.
65. Wang D, Zhang H, Li M, Frid MG, Flockton AR, McKeon BA, Yeager ME, Fini MA, Morrell NW, Pullamsetti SS, et al. MicroRNA-124 controls the proliferative, migratory, and inflammatory phenotype of pulmonary vascular fibroblasts. Circ Res 2014;114:67-78.
66. Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 2010;121:2045-2066.
67. Nogueira-Ferreira R, Ferreira R, Henriques-Coelho T. Cellular interplay in pulmonary arterial hypertension: implications for new therapies. Biochim Biophys Acta 2014;1843:885-893.
68. Fisher EA, Miano JM. Don't judge books by their covers: vascular smooth muscle cells in arterial pathologies. Circulation 2014;129: 1545-1547.
69. Patel MS, Taylor GP, Bharya S, Al-Sanna 'a N, Adatia I, Chitayat D, Suzanne Lewis ME, Human DG. Abnormal pericyte recruitment as a cause for pulmonary hypertension in Adams-Oliver syndrome. Am J Med Genet A 2004;129A:294-299.
70. Ricard N, Tu L, Le Hiress M, Huertas A, Phan C, Thuillet R, Sattler C, Fadel E, Seferian A, Montani D, et al. Increased pericyte coverage mediated by endothelial-derived fibroblast growth factor-2 and interleukin-6 is a source of smooth muscle-like cells in pulmonary hypertension. Circulation 2014;129:1586-1597.
71. Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJG, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 2012;14:249-256.
72. Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 2006; 38:1060-1065.
73. Woods K, Thomson JM, Hammond SM. Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem 2007;282:2130-2134.
74. Davis BN, Hilyard AC, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature 2008;454:56-61.
75. Gamazon ER, Im H-K, Duan S, Lussier YA, Cox NJ, Dolan ME, Zhang W. Exprtarget: an integrative approach to predicting human microRNA targets. PLoS One 2010;5:e13534.
76. Kang H, Davis-Dusenbery BN, Nguyen PH, Lal A, Lieberman J, Van Aelst L, Lagna G, Hata A. Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins. J Biol Chem 2012;287: 3976-3986.
77. 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;115:4944-4950.
78. Schlosser K, White RJ, Stewart DJ. miR-26a linked to pulmonary hypertension by global assessment of circulating extracellular microRNAs. Am J Respir Crit Care Med 2013;188:1472-1475.
79. Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov 2010;9: 775-789.
80. Lindow M, Kauppinen S. Discovering the first microRNA-targeted drug. J Cell Biol 2012;199:407-412.
81. Janssen HLA, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013;368:1685-1694.
82. Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 2014;13:622-638.
83. van Rooij E, Purcell AL, Levin AA. Developing microRNA therapeutics. Circ Res 2012;110:496-507.
84. Kloosterman WP, Lagendijk AK, Ketting RF, Moulton JD, Plasterk RHA. Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol 2007;5: e203.
85. Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005;438:685-689.
86. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A, et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 2005;11:263-270.
87. Wada S, Obika S, Shibata M-A, Yamamoto T, Nakatani M, Yamaoka T, Torigoe H, Harada-Shiba M. Development of a 2′,4′-bna/lna-based sirna for dyslipidemia and assessment of the effects of its chemical modifications in vivo. Mol Ther Nucleic Acids 2012;1:e45.
88. Cui R-R, Li S-J, Liu L-J, Yi L, Liang Q-H, Zhu X, Liu G-Y, Liu Y, Wu S-S, Liao X-B, et al. MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo. Cardiovasc Res 2012;96:320-329.
89. Huang J, Zhao L, Xing L, Chen D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 2010;28:357-364.
90. Zhou X, Li L, Su J, Zhang G. Decreased miR-204 in H. pylori-associated gastric cancer promotes cancer cell proliferation and invasion by targeting SOX4. PLoS One 2014;9:e101457.
91. Ying Z, Li Y, Wu J, Zhu X, Yang Y, Tian H, Li W, Hu B, Cheng S-Y, Li M. Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype. Cancer Res 2013;73:990-999.
92. Kather JN, Friedrich J, Woik N, Sticht C, Gretz N, Hammes H-P, Kroll J. Angiopoietin-1 is regulated by miR-204 and contributes to corneal neovascularization in KLEIP-deficient mice. Invest Ophthalmol Vis Sci 2014;55:4295-4303.
93. Ma L, Deng X, Wu M, Zhang G, Huang J. Down-regulation of miRNA-204 by LMP-1 enhances CDC42 activity and facilitates invasion of EBV-associated nasopharyngeal carcinoma cells. FEBS Lett 2014; 588:1562-1570.
94. Bao W, Wang H-H, Tian F-J, He X-Y, Qiu M-T, Wang J-Y, Zhang H-J, Wang L-H, Wan X-P. A TrkB-STAT3-miR-204-5p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells. Mol Cancer 2013;12:155.
95. Ryan J, Tivnan A, Fay J, Bryan K, Meehan M, Creevey L, Lynch J, Bray IM, O'Meara A, Tracey L, et al. MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer 2012;107:967-976.
96. Qiu YH, Wei YP, Shen NJ, Wang ZC, Kan T, Yu WL, Yi B, Zhang YJ. miR-204 inhibits epithelial to mesenchymal transition by targeting slug in intrahepatic cholangiocarcinoma cells. Cell Physiol Biochem 2013;32:1331-1341.
97. Chen Z, Sangwan V, Banerjee S, Mackenzie T, Dudeja V, Li X, Wang H, Vickers SM, Saluja AK. miR-204 mediated loss of myeloid cell leukemia-1 results in pancreatic cancer cell death. Mol Cancer 2013; 12:105.
98. Xu G, Chen J, Jing G, Shalev A. Thioredoxin-interacting protein regulates insulin transcription through microRNA-204. Nat Med 2013;19:1141-1146.
99. Zhang L, Wang X, Chen P. MiR-204 down regulates SIRT1 and reverts SIRT1-induced epithelial-mesenchymal transition, anoikis resistance and invasion in gastric cancer cells. BMC Cancer 2013;13:290.
100. Shaham O, Gueta K, Mor E, Oren-Giladi P, Grinberg D, Xie Q, Cvekl A, Shomron N, Davis N, Keydar-Prizant M, et al. Pax6 regulates gene expression in the vertebrate lens through miR-204. PLoS Genet 2013;9:e1003357.
101. Imam JS, Plyler JR, Bansal H, Prajapati S, Bansal S, Rebeles J, Chen H-IH, Chang Y-F, Panneerdoss S, Zoghi B, et al. Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization. PLoS One 2012;7:e52397.
102. Wang Y, Li W, Zang X, Chen N, Liu T, Tsonis PA, Huang Y. MicroRNA-204-5p regulates epithelial-to-mesenchymal transition during human posterior capsule opacification by targeting SMAD4. Invest Ophthalmol Vis Sci 2013;54: 323-332.
103. Sacconi A, Biagioni F, Canu V, Mori F, Di Benedetto A, Lorenzon L, Ercolani C, Di Agostino S, Cambria AM, Germoni S, et al. miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis 2012;3:e423.
104. Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, Drew AF, Gallo CA, Plas DR, Biesiada J, Meller J, et al. VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell 2012;21: 532-546.
105. Xiao J, Zhu X, He B, Zhang Y, Kang B, Wang Z, Ni X. MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II. J Biomed Sci 2011;18:35.
106. Li G, Luna C, Qiu J, Epstein DL, Gonzalez P. Role of miR-204 in the regulation of apoptosis, endoplasmic reticulum stress response, and in flammation in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 2011;52:2999-3007.
107. Conte I, Carrella S, Avellino R, Karali M, Marco-Ferreres R, Bovolenta P, Banfi S. miR-204 is required for lens and retinal development via Meis2 targeting. Proc Natl Acad Sci USA 2010; 107:15491-15496.
108. Llobet-Navas D, Rodŕguez-Barrueco R, Castro V, Ugalde AP, Sumazin P, Jacob-Sendler D, Demircan B, Castillo-Martín M, Putcha P, Marshall N, et al. The miR-424(322)/503 cluster orchestrates remodeling of the epithelium in the involuting mammary gland. Genes Dev 2014;28:765-782.
109. Oneyama C, Kito Y, Asai R, Ikeda J, Yoshida T, Okuzaki D, Kokuda R, Kakumoto K, Takayama K, Inoue S, et al. MiR-424/503-mediated Rictor upregulation promotes tumor progression. PLoS One 2013; 8:e80300.
110. Caporali A, Meloni M, Völlenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, et al. Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation 2011; 123:282-291.
111. Sarkar S, Dey BK, Dutta A. MiR-322/424 and -503 are induced during muscle differentiation and promote cell cycle quiescence and differentiation by down-regulation of Cdc25A. Mol Biol Cell 2010; 21:2138-2149.
112. Zhang D, Shi Z, Li M, Mi J. Hypoxia-induced miR-424 decreases tumor sensitivity to chemotherapy by inhibiting apoptosis. Cell Death Dis 2014;5:e1301.
113. Yu L, Ding GF, He C, Sun L, Jiang Y, Zhu L. MicroRNA-424 is down-regulated in hepatocellular carcinoma and suppresses cell migration and invasion through c-Myb. PLoS One 2014;9: e91661.
114. Liu W, Gong Q, Ling J, Zhang W, Liu Z, Quan J. Role of miR-424 on angiogenic potential in human dental pulp cells. J Endod 2014;40: 76-82.
115. Mouillet J-F, Donker RB, Mishima T, Cronqvist T, Chu T, Sadovsky Y. The unique expression and function of miR-424 in human placental trophoblasts. Biol Reprod 2013;89:25.
116. Shen X, Tang J, Hu J, Guo L, Xing Y, Xi T. MiR-424 regulates monocytic differentiation of human leukemia U937 cells by directly targeting CDX2. Biotechnol Lett 2013;35:1799-1806.
117. Zhou R, Gong A-Y, Chen D, Miller RE, Eischeid AN, Chen X-M. Histone deacetylases and NF-kB signaling coordinate expression of CX3CL1 in epithelial cells in response to microbial challenge by suppressing miR-424 and miR-503. PLoS One 2013;8:e65153.
118. Merlet E, Atassi F, Motiani RK, Mougenot N, Jacquet A, Nadaud S, Capiod T, Trebak M, Lompré A-M, Marchand A. miR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat. Cardiovasc Res 2013;98: 458-468.
119. Xu J, Li Y, Wang F, Wang X, Cheng B, Ye F, Xie X, Zhou C, Lu W. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene 2013;32:976-987.
120. Nakashima T, Jinnin M, Etoh T, Fukushima S, Masuguchi S, Maruo K, Inoue Y, Ishihara T, Ihn H. Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: its implications to therapy. PLoS One 2010; 5:e14334.
121. 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-α isoforms and promotes angiogenesis. J Clin Invest 2010;120: 4141-4154.
122. Rosa A, Ballarino M, Sorrentino A, Sthandier O, De Angelis FG, Marchioni M, Masella B, Guarini A, Fatica A, Peschle C, et al. The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation. Proc Natl Acad Sci USA 2007;104:19849-19854.
123. Wang T, Ge G, Ding Y, Zhou X, Huang Z, Zhu W, Shu Y, Liu P. MiR-503 regulates cisplatin resistance of human gastric cancer cell lines by targeting IGF1R and BCL2. Chin Med J (Engl) 2014;127: 2357-2362.
124. Zhang Y, Chen X, Lian H, Liu J, Zhou B, Han S, Peng B, Yin J, Liu W, He X. MicroRNA-503 acts as a tumor suppressor in glioblastoma for multiple antitumor effects by targeting IGF-1R. Oncol Rep 2014; 31:1445-1452.
125. Qiu T, Zhou L, Wang T, Xu J, Wang J, Chen W, Zhou X, Huang Z, Zhu W, Shu Y, et al. miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin by targeting Bcl-2. Int J Mol Med 2013; 32:593-598.
126. Cao S, Xiao L, Rao JN, Zou T, Liu L, Zhang D, Turner DJ, Gorospe M, Wang J-Y. Inhibition of Smurf2 translation by miR-322/503 modulates TGF-β/Smad2 signaling and intestinal epithelial homeostasis. Mol Biol Cell 2014;25: 1234-1243.
127. Yang Y, Liu L, Zhang Y, Guan H, Wu J, Zhu X, Yuan J, Li M. MiR-503 targets PI3K p85 and IKK-β and suppresses progression of nonsmall cell lung cancer. Int J Cancer 2014;135:1531-1542.
128. Li N, Zhang F, Li S, Zhou S. Epigenetic silencing of MicroRNA-503 regulates FANCA expression in non-small cell lung cancer cell. Biochem Biophys Res Commun 2014;444:611-616.
129. Chen C, Cheng P, Xie H, Zhou H-D, Wu X-P, Liao E-Y, Luo X-H. MiR-503 regulates osteoclastogenesis via targeting RANK. J Bone Miner Res 2014;29:338-347.
130. Xu Y-Y, Wu H-J, Ma H-D, Xu L-P, Huo Y, Yin L-R. MicroRNA-503 suppresses proliferation and cell-cycle progression of endometrioid endometrial cancer by negatively regulating cyclin D1. FEBS J 2013;280:3768-3779.
131. Cui Y-H, Xiao L, Rao JN, Zou T, Liu L, Chen Y, Turner DJ, Gorospe M, Wang J-Y. miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies. Mol Biol Cell 2012;23:151-162.