MicroRNA-138 and MicroRNA-25 down-regulate mitochondrial calcium uniporter, causing the pulmonary arterial hypertension cancer phenotype

American Journal of Respiratory and Critical Care Medicine

Volumn 195, Issue 4, 2017, Pages 515-529

  Hong, Zhigang ^a   Chen, Kuang Hueih ^a   DasGupta, Asish ^a   Potus, Francois ^b   Dunham Snary, Kimberly ^a   Bonnet, Sebastien ^b   Tian, Lian ^a   Fu, Jennifer ^a   Breuils Bonnet, Sandra ^b   Provencher, Steeve ^b   Wu, Danchen ^a   Mewburn, Jeffrey ^a   Ormiston, Mark L ^a   Archer, Stephen L ^a  

^a QUEEN S UNIVERSITY   (Canada)

^b UNIVERSITÉ LAVAL   (Canada)

Author keywords

CAMP response element binding protein; MicroRNA 25 and 138 5p; Mitochondrial calcium uptake protein 1; Pyruvate dehydrogenase

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 2; CALCIUM; MICRORNA; MICRORNA 138; MICRORNA 25; MITOCHONDRIAL CALCIUM UNIPORTER COMPLEX; MITOCHONDRIAL CALCIUM UPTAKE PROTEIN 1; MITOCHONDRIAL PROTEIN; PYRUVATE DEHYDROGENASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; CALCIUM BINDING PROTEIN; CALCIUM CHANNEL; CARRIER PROTEIN; CATION TRANSPORT PROTEIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; MICU1 PROTEIN, HUMAN; MIRN138 MICRORNA, RAT; MIRN25 MICRORNA, HUMAN; MIRN25 MICRORNA, RAT; MITOCHONDRIAL CALCIUM UNIPORTER; PYRUVATE DEHYDROGENASE COMPLEX;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CELL ISOLATION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVITY; GLUCOSE OXIDATION; HUMAN; IN VIVO STUDY; MALIGNANT NEOPLASM; MITOCHONDRIAL DYNAMICS; MONOCROTALINE-INDUCED PULMONARY HYPERTENSION; NEBULIZATION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PULMONARY ARTERY SMOOTH MUSCLE CELL; PULMONARY HYPERTENSION; RAT; UPREGULATION; ANIMAL; CASE CONTROL STUDY; CELL CULTURE TECHNIQUE; CYTOSOL; DISEASE MODEL; DRUG EFFECTS; GENE THERAPY; GENETICS; GLYCOLYSIS; HYPERTENSION, PULMONARY; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PROCEDURES; PULMONARY ARTERY; VASCULAR SMOOTH MUSCLE;

ANIMALS; APOPTOSIS; CALCIUM; CALCIUM CHANNELS; CALCIUM-BINDING PROTEINS; CASE-CONTROL STUDIES; CATION TRANSPORT PROTEINS; CELL CULTURE TECHNIQUES; CELL PROLIFERATION; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; CYTOSOL; DISEASE MODELS, ANIMAL; DOWN-REGULATION; GENETIC THERAPY; GLYCOLYSIS; HUMANS; HYPERTENSION, PULMONARY; MICRORNAS; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MUSCLE, SMOOTH, VASCULAR; PHENOTYPE; PULMONARY ARTERY; PYRUVATE DEHYDROGENASE COMPLEX; RATS; UP-REGULATION;

EID: 85014956067     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201604-0814OC     Document Type: Article

References (56)

1. Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 2010; 121:2045-2066.
2. Thenappan T, Shah SJ, Rich S, Gomberg-Maitland M. A USA-based registry for pulmonary arterial hypertension: 1982-2006. Eur Respir J 2007; 30:1103-1110.
3. Sutendra G, Michelakis ED. The metabolic basis of pulmonary arterial hypertension. Cell Metab 2014; 19:558-573.
4. Marsboom G, Toth PT, Ryan JJ, Hong Z, Wu X, Fang YH, Thenappan T, Piao L, Zhang HJ, Pogoriler J, et al. Dynamin-related protein 1-mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension. Circ Res 2012; 110:1484-1497.
5. Rehman J, Zhang HJ, Toth PT, Zhang Y, Marsboom G, Hong Z, Salgia R, Husain AN, Wietholt C, Archer SL. Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB J 2012; 26:2175-2186.
6. Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JG, Weir EK. Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol 2008; 294:H570-H578.
7. Archer SL, Marsboom G, Kim GH, Zhang HJ, Toth PT, Svensson EC, Dyck JR, Gomberg-Maitland M, Thébaud B, Husain AN, et al. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation 2010; 121: 2661-2671.
8. 18F-fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of pulmonary arterial hypertension. Am J Respir Crit Care Med 2012; 185:670-679.
9. Xu W, Erzurum SC. Endothelial cell energy metabolism, proliferation, and apoptosis in pulmonary hypertension. Compr Physiol 2011; 1: 357-372.
10. Warburg O. On the origin of cancer cells. Science 1956; 123: 309-314.
11. Ryan JJ, Marsboom G, Fang YH, Toth PT, Morrow E, Luo N, Piao L, Hong Z, Ericson K, Zhang HJ, et al. PGC1α-mediated mitofusin-2 deficiency in female rats and humans with pulmonary arterial hypertension. Am J Respir Crit Care Med 2013; 187: 865-878.
12. Yuan JX, Aldinger AM, Juhaszova M, Wang J, Conte JV Jr, Gaine SP, Orens JB, Rubin LJ. Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 1998; 98: 1400-1406.
13. Pozeg ZI, Michelakis ED, McMurtry MS, Thébaud B, Wu XC, Dyck JR, Hashimoto K, Wang S, Moudgil R, Harry G, et al. In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 2003; 107:2037-2044.
14. Yu Y, Keller SH, Remillard CV, Safrina O, Nicholson A, Zhang SL, Jiang W, Vangala N, Landsberg JW, Wang JY, et al. A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 2009; 119:2313-2322.
15. Pan X, Liu J, Nguyen T, Liu C, Sun J, Teng Y, Fergusson MM, Rovira II, Allen M, Springer DA, et al. The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. Nat Cell Biol 2013; 15:1464-1472.
16. Denton RM, McCormack JG, Edgell NJ. Role of calcium ions in the regulation of intramitochondrial metabolism. Effects of Na+, Mg2+ and ruthenium red on the Ca2+-stimulated oxidation of oxoglutarate and on pyruvate dehydrogenase activity in intact rat heart mitochondria. Biochem J 1980; 190:107-117.
17. McCormack JG, Denton RM. The role of intramitochondrial Ca2+ in the regulation of oxidative phosphorylation in mammalian tissues. Biochem Soc Trans 1993; 21:793-799.
18. De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 2011; 476:336-340.
19. Raffaello A, De Stefani D, Sabbadin D, Teardo E, Merli G, Picard A, Checchetto V, Moro S, Szabò I, Rizzuto R. The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J 2013; 32:2362-2376.
20. Palty R, Silverman WF, Hershfinkel M, Caporale T, Sensi SL, Parnis J, Nolte C, Fishman D, Shoshan-Barmatz V, Herrmann S, et al. NCLX is an essential component of mitochondrial Na+/Ca2+ exchange. Proc Natl Acad Sci USA 2010; 107:436-441.
21. Takeuchi A, Kim B, Matsuoka S. The destiny of Ca(2+) released by mitochondria. J Physiol Sci 2015; 65:11-24.
22. Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature 2004; 427: 360-364.
23. Samanta K, Douglas S, Parekh AB. Mitochondrial calcium uniporter MCU supports cytoplasmic Ca2+ oscillations, store-operated Ca2+ entry and Ca2+-dependent gene expression in response to receptor stimulation. PLoS One 2014; 9:e101188.
24. Perocchi F, Gohil VM, Girgis HS, Bao XR, McCombs JE, Palmer AE, Mootha VK. MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature 2010; 467:291-296.
25. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 2011; 476:341-345.
26. Kamer KJ, Mootha VK. The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol 2015; 16:545-553.
27. Pacher P, Hajnóczky G. Propagation of the apoptotic signal by mitochondrial waves. EMBO J 2001; 20:4107-4121.
28. Shanmughapriya S, Rajan S, Hoffman NE, Zhang X, Guo S, Kolesar JE, Hines KJ, Ragheb J, Jog NR, Caricchio R, et al. Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU. Sci Signal 2015; 8:ra23.
29. Marchi S, Lupini L, Patergnani S, Rimessi A, Missiroli S, Bonora M, Bononi A, Corrà F, Giorgi C, De Marchi E, et al. Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25. Curr Biol 2013; 23:58-63.
30. Pan L, Huang BJ, Ma XE, Wang SY, Feng J, Lv F, Liu Y, Liu Y, Li CM, Liang DD, et al. MiR-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter. Int J Mol Sci 2015; 16:5420-5433.
31. Wang W, Kwon EJ, Tsai LH. MicroRNAs in learning, memory, and neurological diseases. Learn Mem 2012; 19:359-368.
32. Parker D, Ferreri K, Nakajima T, LaMorte VJ, Evans R, Koerber SC, Hoeger C, Montminy MR. Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism. Mol Cell Biol 1996; 16:694-703.
33. Dromparis P, Paulin R, Sutendra G, Qi AC, Bonnet S, Michelakis ED. Uncoupling protein 2 deficiency mimics the effects of hypoxia and endoplasmic reticulum stress on mitochondria and triggers pseudohypoxic pulmonary vascular remodeling and pulmonary hypertension. Circ Res 2013; 113:126-136.
34. Archer SL. Mitochondrial dynamics: mitochondrial fission and fusion in human diseases. N Engl J Med 2013; 369: 2236-2251.
35. Han XJ, Lu YF, Li SA, Kaitsuka T, Sato Y, Tomizawa K, Nairn AC, Takei K, Matsui H, Matsushita M. CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial morphology. J Cell Biol 2008; 182:573-585.
36. Boucherat O, Potus F, Bonnet S. microRNA and pulmonary hypertension. Adv Exp Med Biol 2015; 888:237-252.
37. Grant JS, White K, MacLean MR, Baker AH. MicroRNAs in pulmonary arterial remodeling. Cell Mol Life Sci 2013; 70: 4479-4494.
38. Potus F, Malenfant S, Graydon C, Mainguy V, Tremblay È, Breuils-Bonnet S, Ribeiro F, Porlier A, Maltais F, Bonnet S, et al. Impaired angiogenesis and peripheral muscle microcirculation loss contribute to exercise intolerance in pulmonary arterial hypertension. Am J Respir Crit Care Med 2014; 190:318-328.
39. Potus F, Ruffenach G, Dahou A, Thebault C, Breuils-Bonnet S, Tremblay È, Nadeau V, Paradis R, Graydon C, Wong R, et al. Downregulation of MicroRNA-126 contributes to the failing right ventricle in pulmonary arterial hypertension. Circulation 2015; 132: 932-943.
40. Li S, Ran Y, Zhang D, Chen J, Li S, Zhu D. MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1. Biochem J 2013; 452:281-291.
41. Bertero T, Cottrill K, Krauszman A, Lu Y, Annis S, Hale A, Bhat B, Waxman AB, Chau BN, Kuebler WM, et al. The microRNA-130/301 family controls vasoconstriction in pulmonary hypertension. J Biol Chem 2015; 290:2069-2085.
42. Huber LC, Ulrich S, Leuenberger C, Gassmann M, Vogel J, von Blotzheim LG, Speich R, Kohler M, Brock M. Featured article: microRNA-125a in pulmonary hypertension: regulator of a proliferative phenotype of endothelial cells. Exp Biol Med (Maywood) 2015; 240:1580-1589.
43. 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.
44. 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.
45. + channel in arterial smooth muscle cells. J Cell Biochem 2014; 115: 1196-1205.
46. 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.
47. 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.
48. Patergnani S, Giorgi C, Maniero S, Missiroli S, Maniscalco P, Bononi I, Martini F, Cavallesco G, Tognon M, Pinton P. The endoplasmic reticulum mitochondrial calcium cross talk is downregulated in malignant pleural mesothelioma cells and plays a critical role in apoptosis inhibition. Oncotarget 2015; 6: 23427-23444.
49. Sen A, Ren S, Lerchenmüller C, Sun J, Weiss N, Most P, Peppel K. MicroRNA-138 regulates hypoxia-induced endothelial cell dysfunction by targeting S100A1. PLoS One 2013; 8: e78684.
50. Meloche J, Pflieger A, Vaillancourt M, Paulin R, Potus F, Zervopoulos S, Graydon C, Courboulin A, Breuils-Bonnet S, Tremblay E, et al. Role for DNA damage signaling in pulmonary arterial hypertension. Circulation 2014; 129:786-797.
51. Klemm DJ, Watson PA, Frid MG, Dempsey EC, Schaack J, Colton LA, Nesterova A, Stenmark KR, Reusch JE. cAMP response elementbinding protein content is a molecular determinant of smooth muscle cell proliferation and migration. J Biol Chem 2001; 276: 46132-46141.
52. Paulin R, Meloche J, Courboulin A, Lambert C, Haromy A, Courchesne A, Bonnet P, Provencher S, Michelakis ED, Bonnet S. Targeting cell motility in pulmonary arterial hypertension. Eur Respir J 2014; 43:531-544.
53. Holmström KM, Pan X, Liu JC, Menazza S, Liu J, Nguyen TT, Pan H, Parks RJ, Anderson S, Noguchi A, et al. Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter. J Mol Cell Cardiol 2015; 85:178-182.
54. Santulli G, Xie W, Reiken SR, Marks AR. Mitochondrial calcium overload is a key determinant in heart failure. Proc Natl Acad Sci USA 2015; 112:11389-11394.
55. Yan H, Zhang D, Hao S, Li K, Hang CH. Role of mitochondrial calcium uniporter in early brain injury after experimental subarachnoid hemorrhage. Mol Neurobiol 2015; 52:1637-1647.
56. Palmer AE, Tsien RY. Measuring calcium signaling using genetically targetable fluorescent indicators. Nat Protoc 2006; 1:1057-1065.