ES2575868T3 - Expresión de miARN en microvesículas de sangre periférica humana y sus usos - Google Patents

Expresión de miARN en microvesículas de sangre periférica humana y sus usos Download PDF

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ES2575868T3
ES2575868T3 ES13161709.4T ES13161709T ES2575868T3 ES 2575868 T3 ES2575868 T3 ES 2575868T3 ES 13161709 T ES13161709 T ES 13161709T ES 2575868 T3 ES2575868 T3 ES 2575868T3
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Clay B. Marsh
Melissa G Piper
Noura Ismail
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Ohio State University Research Foundation
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Abstract

Un método para diagnosticar o pronosticar cáncer colorrectal en un sujeto, que comprende: i) aislar microvesículas en una muestra del sujeto; ii) determinar el nivel de al menos los siguientes regulados positivamente y al menos los siguientes miR regulados negativamente en las microvesículas aisladas; en donde los miR regulados positivamente comprenden miR-19a, miR-21, miR-127, miR-31, miR-96, miR-135b y miR-183; y los miR regulados negativamente comprenden miR-30c, miR-133a, miR-143, miR-133b y miR-145; y iii) comparar el nivel de los miR con un control, en donde una alteración del nivel de los miR, en relación con el del control, es diagnóstico del cáncer colorrectal.

Description

imagen1
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Otras técnicas para medir la expresión génica de miR también están dentro de la experiencia de la técnica, e incluyen diversas técnicas para medir velocidades de transcripción y degradación de ARN.
La presente divulgación también proporciona procedimientos para diagnosticar si un sujeto tiene, o está en riesgo de
5 desarrollar, un trastorno particular con un pronóstico adverso. En este procedimiento, el nivel de al menos un producto génico de miR, que se asocia con un pronóstico adverso en un trastorno particular, se mide por transcripción inversa de ARN a partir de una muestra de ensayo obtenida del sujeto para proporcionar un conjunto de oligodesoxinucleótidos diana. Los oligodesoxinucleótidos diana se hibridan después con uno o más oligonucleótidos sonda específicos de miARN (por ejemplo, una micromatriz que comprende oligonucleótidos sonda específicos de miARN) para proporcionar un perfil de hibridación para la muestra de ensayo, y el perfil de hibridación de la muestra de ensayo se compara con un perfil de hibridación generado a partir de una muestra de control. Una alteración en la señal de al menos un miARN en la muestra de ensayo en relación con la muestra de control es indicativa de que el sujeto tiene, o está en riesgo de desarrollar, un trastorno particular con un pronóstico adverso.
15 En algunos casos, puede ser deseable determinar simultáneamente el nivel de expresión de una pluralidad de diferentes productos génicos de miR en una muestra. En otros casos, puede ser deseable determinar el nivel de expresión de los transcritos de todos los genes de miR conocidos correlacionados con un trastorno particular. Evaluar los niveles de expresión específicos para cientos de genes o productos génicos de miR consume tiempo y requiere una gran cantidad de ARN total (por ejemplo, al menos 20 µg para cada transferencia de Northern) y técnicas autorradiográficas que requieren isótopos radiactivos.
Para superar estas limitaciones, puede construirse una oligobiblioteca, en formato de microplaca (es decir, una micromatriz), que contenga un conjunto de sondas oligonucleotídicas (por ejemplo, oligodesoxinucleotídica) que sean específicas para un conjunto de genes de miR. Usando dicha micromatriz, el nivel de expresión de múltiples
25 microARN en una muestra biológica puede determinarse por transcripción inversa de los ARN para generar un conjunto de oligodesoxinucleótidos diana, e hibridarlos para explorar los oligonucleótidos en la micromatriz para generar un perfil de hibridación o expresión. El perfil de hibridación de la muestra de ensayo puede compararse después con el de una muestra de control para determinar qué microARN tienen un nivel de expresión alterado. Como se usa en el presente documento, “oligonucleótido sonda” o “oligodesoxinucleótido sonda” se refiere a un oligonucleótido que es capaz de hibridar con un oligonucleótido diana. ”Oligonucleótido diana” u “oligodesoxinucleótido diana” se refiere a una molécula para detectar (por ejemplo, mediante hibridación). Por “oligonucleótido sonda específico de miR” u “oligonucleótido sonda específico para un miR” se entiende un oligonucleótido sonda que tiene una secuencia seleccionada para hibridar con un producto génico de miR específico, o con un transcrito inverso del producto génico de miR específico.
35 Un “perfil de expresión” o “perfil de hibridación” de una muestra particular es esencialmente una identificación del estado de la muestra; mientras que dos estados pueden tener cualquier gen particular expresado de forma similar, la evaluación de varios genes simultáneamente permite la generación de un perfil de expresión génica que es único para el estado de la célula. Es decir, pueden distinguirse muestras normales de muestras que presentan trastorno correspondiente. Dentro de dichas muestras que presentan trastorno, pueden determinarse diferentes estados de pronóstico (por ejemplo, buenas o malas perspectivas de supervivencia a largo plazo). Comparando los perfiles de expresión de muestras que presentan trastorno en diferentes estados, se obtiene información con respecto a qué genes son importantes (incluyendo tanto regulación positiva como regulación negativa de genes) en cada uno de estos estados.
45 La identificación de secuencias que se expresan de forma diferencial en muestras que presentan trastorno, así como la expresión diferencial que da diferentes resultados de pronóstico, permite el uso de esta información de varias maneras. Por ejemplo, puede evaluarse un régimen de tratamiento particular (por ejemplo, para determinar si un fármaco quimioterapéutico actúa para mejorar el pronóstico a largo plazo en un sujeto particular). De forma similar, puede realizarse o confirmarse el diagnóstico comparando muestras de un sujeto con perfiles de expresión conocidos. Además, estos perfiles de expresión génica (o genes individuales) permiten la exploración de candidatos farmacológicos que suprimen el perfil de expresión del trastorno particular o convierten un perfil de pronóstico malo en un perfil de mejor pronóstico.
55 Las alteraciones en el nivel de uno o más productos génicos de miR en células pueden dar como resultado la desregulación de una o más dianas pretendidas para estos miR, lo que puede conducir a un trastorno particular. Por lo tanto, alterar el nivel del producto génico de miR (por ejemplo, reduciendo el nivel de un miR que está regulado positivamente en células que muestran un trastorno, aumentando el nivel de un miR que está regulado negativamente en células que presentan trastorno) puede tratar exitosamente el trastorno.
En consecuencia, la presente divulgación abarca procedimientos para tratar un trastorno en un sujeto, en el que al menos un producto génico de miR está desregulado (por ejemplo, regulado negativamente, regulado positivamente) en las células del sujeto. En una realización de la presente divulgación, el nivel de al menos un producto génico de miR en una muestra de ensayo es mayor que el nivel del producto génico de miR correspondiente en una muestra
65 de control o referencia. En otra realización de la presente divulgación, el nivel de al menos un producto génico de miR en una muestra de ensayo es menor que el nivel del producto génico de miR correspondiente en una muestra
imagen6
imagen7
imagen8
imagen9
hsalet7d*
MIMAT0004484 CUAUACGACCUGCUGCCUUUCU
hsalet7e
MIMAT0000066 UGAGGUAGGAGGUUGUAUAGUU 11
hsalet7e*
MIMAT0004485 CUAUACGGCCUCCUAGCUUUCC 12
hsalet7f1
MIMAT0000067 UGAGGUAGUAGAUUGUAUAGUU 13
hsalet7f1*
MIMAT0004486 CUAUACAAUCUAUUGCCUUCCC 14
hsalet7f2
MIMAT0000067 UGAGGUAGUAGAUUGUAUAGUU 15
hsalet7f2*
MIMAT0004487 CUAUACAGUCUACUGUCUUUCC 16
hsalet7g
MIMAT0000414 UGAGGUAGUAGUUUGUACAGUU 17
hsalet7g*
MIMAT0004584 CUGUACAGGCCACUGCCUUGC 18
hsalet7i
MIMAT0000415 UGAGGUAGUAGUUUGUGCUGUU 19
hsalet7i*
MIMAT0004585 CUGCGCAAGCUACUGCCUUGCU
hsamir0091
MIMAT0000441 UCUUUGGUUAUCUAGCUGUAUGA 21
hsamir0091*
MIMAT0000442 AUAAAGCUAGAUAACCGAAAGU 22
hsamir0092
MIMAT0000441 UCUUUGGUUAUCUAGCUGUAUGA 23
hsamir0093
MIMAT0000441 UCUUUGGUUAUCUAGCUGUAUGA 24
hsamir010a
MIMAT0000253 UACCCUGUAGAUCCGAAUUUGUG 25
hsamir010a*
MIMAT0004555 CAAAUUCGUAUCUAGGGGAAUA 26
hsamir015a
MIMAT0000068 UAGCAGCACAUAAUGGUUUGUG 27
hsamir015b
MIMAT0000417 UAGCAGCACAUCAUGGUUUACA 28
hsamir015b*
MIMAT0004586 CGAAUCAUUAUUUGCUGCUCUA 29
hsamir0161
MIMAT0000069 UAGCAGCACGUAAAUAUUGGCG
hsamir0161*
MIMAT0004489 CCAGUAUUAACUGUGCUGCUGA 31
hsamir0162
MIMAT0000069 UAGCAGCACGUAAAUAUUGGCG 32
hsamir0162*
MIMAT0004518 CCAAUAUUACUGUGCUGCUUUA 33
hsamir0173p
MIMAT0000071 ACUGCAGUGAAGGCACUUGUAG 34
hsamir0175p
MIMAT0000070 CAAAGUGCUUACAGUGCAGGUAG 35
hsamir018a
MIMAT0000072 UAAGGUGCAUCUAGUGCAGAUAG 36
hsamir018a*
MIMAT0002891 ACUGCCCUAAGUGCUCCUUCUGG 37
hsamir019a
MIMAT0000073 UGUGCAAAUCUAUGCAAAACUGA 38
hsamir019b1
MIMAT0000074 UGUGCAAAUCCAUGCAAAACUGA 39
hsamir019b1*
MIMAT0004491 AGUUUUGCAGGUUUGCAUCCAGC
hsamir019b2
MIMAT0000074 UGUGCAAAUCCAUGCAAAACUGA 41
hsamir019b2*
MIMAT0004492 AGUUUUGCAGGUUUGCAUUUCA 42
hsamir020a
MIMAT0000075 UAAAGUGCUUAUAGUGCAGGUAG 43
hsamir020a*
MIMAT0004493 ACUGCAUUAUGAGCACUUAAAG 44
hsamir020b
MIMAT0001413 CAAAGUGCUCAUAGUGCAGGUAG 45
hsamir021
MIMAT0000076 UAGCUUAUCAGACUGAUGUUGA 46
hsamir021*
MIMAT0004494 CAACACCAGUCGAUGGGCUGU 47
hsamir023a
MIMAT0000078 AUCACAUUGCCAGGGAUUUCC 48
hsamir023a*
MIMAT0004496 GGGGUUCCUGGGGAUGGGAUUU 49
hsamir023b
MIMAT0004587 UGGGUUCCUGGCAUGCUGAUUU
hsamir0241
MIMAT0000080 UGGCUCAGUUCAGCAGGAACAG 51
hsamir0241*
MIMAT0000079 UGCCUACUGAGCUGAUAUCAGU 52
hsamir0242
MIMAT0000080 UGGCUCAGUUCAGCAGGAACAG 53
hsamir0242*
MIMAT0004497 UGCCUACUGAGCUGAAACACAG 54
hsamir025
MIMAT0000081 CAUUGCACUUGUCUCGGUCUGA 55
hsamir025*
MIMAT0004498 AGGCGGAGACUUGGGCAAUUG 56
hsamir026a1
MIMAT0000082 UUCAAGUAAUCCAGGAUAGGCU 57
hsamir026a1*
MIMAT0004499 CCUAUUCUUGGUUACUUGCACG 58
hsamir026a2
MIMAT0000082 UUCAAGUAAUCCAGGAUAGGCU 59
hsamir026a2*
MIMAT0004681 CCUAUUCUUGAUUACUUGUUUC 60
hsamir026b
MIMAT0000083 UUCAAGUAAUUCAGGAUAGGU 61
hsamir026b*
MIMAT0004500 CCUGUUCUCCAUUACUUGGCUC 62
hsamir027a
MIMAT0000084 UUCACAGUGGCUAAGUUCCGC 63
hsamir027a*
MIMAT0004501 AGGGCUUAGCUGCUUGUGAGCA 64
hsamir027b
MIMAT0000419 UUCACAGUGGCUAAGUUCUGC 65
hsamir027b*
MIMAT0004588 AGAGCUUAGCUGAUUGGUGAAC 66
hsamir0283p
MIMAT0004502 CACUAGAUUGUGAGCUCCUGGA 67
hsamir0285p
MIMAT0000085 AAGGAGCUCACAGUCUAUUGAG 68
hsamir029a
MIMAT0000086 UAGCACCAUCUGAAAUCGGUUA 69
hsamir029a*
MIMAT0004503 ACUGAUUUCUUUUGGUGUUCAG 70
hsamir029b1
MIMAT0000100 UAGCACCAUUUGAAAUCAGUGUU 71
hsamir029b1*
MIMAT0004514 GCUGGUUUCAUAUGGUGGUUUAGA 72
hsamir029b2
MIMAT0000100 UAGCACCAUUUGAAAUCAGUGUU 73
hsamir029b2*
MIMAT0004515 CUGGUUUCACAUGGUGGCUUAG 74
hsamir029b3
MIMAT0000100 UAGCACCAUUUGAAAUCAGUGUU 75
hsamir029c
MIMAT0000681 UAGCACCAUUUGAAAUCGGUUA 76
hsamir030a
MIMAT0000087 UGUAAACAUCCUCGACUGGAAG 77
hsamir030a*
MIMAT0000088 CUUUCAGUCGGAUGUUUGCAGC 78
hsamir030b
MIMAT0000420 UGUAAACAUCCUACACUCAGCU 79
hsamir030b*
MIMAT0004589 CUGGGAGGUGGAUGUUUACUUC 80
hsamir030c1
MIMAT0000244 UGUAAACAUCCUACACUCUCAGC 81
hsamir030c2
MIMAT0000244 UGUAAACAUCCUACACUCUCAGC 82
hsamir030c2*
MIMAT0004550 CUGGGAGAAGGCUGUUUACUCU 83
hsamir030d
MIMAT0000245 UGUAAACAUCCCCGACUGGAAG 84
hsamir030d*
MIMAT0004551 CUUUCAGUCAGAUGUUUGCUGC 85
hsamir031
MIMAT0000089 AGGCAAGAUGCUGGCAUAGCU 86
hsamir031*
MIMAT0004504 UGCUAUGCCAACAUAUUGCCAU 87
hsamir032
MIMAT0000090 UAUUGCACAUUACUAAGUUGCA 88
hsamir032*
MIMAT0004505 CAAUUUAGUGUGUGUGAUAUUU 89
hsamir034a
MIMAT0000255 UGGCAGUGUCUUAGCUGGUUGU 90
hsamir034a*
MIMAT0004557 CAAUCAGCAAGUAUACUGCCCU 91
hsamir092a1
MIMAT0000092 UAUUGCACUUGUCCCGGCCUGU 92
hsamir092a1*
MIMAT0004507 AGGUUGGGAUCGGUUGCAAUGCU 93
hsamir093
MIMAT0000093 CAAAGUGCUGUUCGUGCAGGUAG 94
hsamir093*
MIMAT0004509 ACUGCUGAGCUAGCACUUCCCG 95
hsamir095
MIMAT0000094 UUCAACGGGUAUUUAUUGAGCA 96
hsamir096
MIMAT0000095 UUUGGCACUAGCACAUUUUUGCU 97
hsamir096*
MIMAT0004510 AAUCAUGUGCAGUGCCAAUAUG 98
hsamir098
MIMAT0000096 UGAGGUAGUAAGUUGUAUUGUU 99
hsamir099b
MIMAT0000689 CACCCGUAGAACCGACCUUGCG 100
hsamir099b*
MIMAT0004678 CAAGCUCGUGUCUGUGGGUCCG 101
hsamir100
MIMAT0000098 AACCCGUAGAUCCGAACUUGUG 102
hsamir100*
MIMAT0004512 CAAGCUUGUAUCUAUAGGUAUG 103
hsamir1031
MIMAT0000101 AGCAGCAUUGUACAGGGCUAUGA 104
hsamir1032
MIMAT0000101 AGCAGCAUUGUACAGGGCUAUGA 105
hsamir1051
MIMAT0000102 UCAAAUGCUCAGACUCCUGUGGU 106
hsamir1051*
MIMAT0004516 ACGGAUGUUUGAGCAUGUGCUA 107
hsamir1052
MIMAT0000102 UCAAAUGCUCAGACUCCUGUGGU 108
hsamir1052*
MIMAT0004516 ACGGAUGUUUGAGCAUGUGCUA 109
hsamir106a
MIMAT0000103 AAAAGUGCUUACAGUGCAGGUAG 110
hsamir106a*
MIMAT0004517 CUGCAAUGUAAGCACUUCUUAC 111
hsamir106b
MIMAT0000680 UAAAGUGCUGACAGUGCAGAU 112
hsamir106b*
MIMAT0004672 CCGCACUGUGGGUACUUGCUGC 113
hsamir107
MIMAT0000104 AGCAGCAUUGUACAGGGCUAUCA 114
hsamir122
MIMAT0000421 UGGAGUGUGACAAUGGUGUUUG 115
hsamir122*
MIMAT0004590 AACGCCAUUAUCACACUAAAUA 116
hsamir125a3p
MIMAT0004602 ACAGGUGAGGUUCUUGGGAGCC 117
hsamir125a5p
MIMAT0000443 UCCCUGAGACCCUUUAACCUGUGA 118
hsamir125b1
MIMAT0000423 UCCCUGAGACCCUAACUUGUGA 119
hsamir125b1*
MIMAT0004592 ACGGGUUAGGCUCUUGGGAGCU 120
hsamir125b2
MIMAT0000423 UCCCUGAGACCCUAACUUGUGA 121
hsamir125b2*
MIMAT0004603 UCACAAGUCAGGCUCUUGGGAC 122
hsamir126
MIMAT0000445 UCGUACCGUGAGUAAUAAUGCG 123
hsamir126*
MIMAT0000444 CAUUAUUACUUUUGGUACGCG 124
hsamir1273p
MIMAT0000446 UCGGAUCCGUCUGAGCUUGGCU 125
hsamir1275p
MIMAT0004604 CUGAAGCUCAGAGGGCUCUGAU 126
hsamir1281
MIMAT0000424 UCACAGUGAACCGGUCUCUUU 127
hsamir1282
MIMAT0000424 UCACAGUGAACCGGUCUCUUU 128
hsamir130
MIMAT0000425 CAGUGCAAUGUUAAAAGGGCAU 129
hsamir130*
MIMAT0004593 UUCACAUUGUGCUACUGUCUGC 130
hsamir130b
MIMAT0000691 CAGUGCAAUGAUGAAAGGGCAU 131
hsamir130b*
MIMAT0004680 ACUCUUUCCCUGUUGCACUAC 132
hsamir132
MIMAT0000426 UAACAGUCUACAGCCAUGGUCG 133
hsamir132*
MIMAT0004594 ACCGUGGCUUUCGAUUGUUACU 134
hsamir133a1
MIMAT0000427 UUUGGUCCCCUUCAACCAGCUG 135
hsamir133a2
MIMAT0000427 UUUGGUCCCCUUCAACCAGCUG 136
hsamir133b
MIMAT0000770 UUUGGUCCCCUUCAACCAGCUA 137
hsamir134
MIMAT0000447 UGUGACUGGUUGACCAGAGGGG 138
hsamir135b
MIMAT0000758 UAUGGCUUUUCAUUCCUAUGUGA 139
hsamir135b*
MIMAT0004698 AUGUAGGGCUAAAAGCCAUGGG 140
hsamir1403p
MIMAT0004397 UACCACAGGGUAGAACCACGG 141
hsamir1405p
MIMAT0000431 CAGUGGUUUUACCCUAUGGUAG 142
hsamir1423p
MIMAT0000434 UGUAGUGUUUCCUACUUUAUGGA 143
hsamir1425p
MIMAT0000433 CAUAAAGUAGAAAGCACUACU 144
hsamir143
MIMAT0000435 UGAGAUGAAGCACUGUAGCUC 145
hsamir143*
MIMAT0004599 GGUGCAGUGCUGCAUCUCUGGU 146
hsamir145
MIMAT0000437 GUCCAGUUUUCCCAGGAAUCCCU 147
hsamir145*
MIMAT0004601 GGAUUCCUGGAAAUACUGUUCU 148
hsamir146a
MIMAT0000449 UGAGAACUGAAUUCCAUGGGUU 149
hsamir146a*
MIMAT0004608 CCUCUGAAAUUCAGUUCUUCAG 150
hsamir146b3p
MIMAT0004766 UGCCCUGUGGACUCAGUUCUGG 151
hsamir146b5p
MIMAT0002809 UGAGAACUGAAUUCCAUAGGCU 152
hsamir147
MIMAT0000251 GUGUGUGGAAAUGCUUCUGC 153
hsamir148a
MIMAT0000243 UCAGUGCACUACAGAACUUUGU 154
hsamir148a*
MIMAT0004549 AAAGUUCUGAGACACUCCGACU 155
hsamir148b
MIMAT0000759 UCAGUGCAUCACAGAACUUUGU 156
hsamir148b*
MIMAT0004699 AAGUUCUGUUAUACACUCAGGC 157
hsamir149
MIMAT0000450 UCUGGCUCCGUGUCUUCACUCCC 158
hsamir149*
MIMAT0004609 AGGGAGGGACGGGGGCUGUGC 159
hsamir150
MIMAT0000451 UCUCCCAACCCUUGUACCAGUG 160
hsamir150*
MIMAT0004610 CUGGUACAGGCCUGGGGGACAG 161
hsamir1513p
MIMAT0000757 CUAGACUGAAGCUCCUUGAGG 162
hsamir1515p
MIMAT0004697 UCGAGGAGCUCACAGUCUAGU 163
hsamir155
MIMAT0000646 UUAAUGCUAAUCGUGAUAGGGGU 164
hsamir155*
MIMAT0004658 CUCCUACAUAUUAGCAUUAACA 165
hsamir1811
MIMAT0000256 AACAUUCAACGCUGUCGGUGAGU 166
hsamir181a1*
MIMAT0000270 ACCAUCGACCGUUGAUUGUACC 167
hsamir181a2
MIMAT0000256 AACAUUCAACGCUGUCGGUGAGU 168
hsamir181a2*
MIMAT0004558 ACCACUGACCGUUGACUGUACC 169
hsamir181b1
MIMAT0000257 AACAUUCAUUGCUGUCGGUGGGU 170
hsamir181b2
MIMAT0000257 AACAUUCAUUGCUGUCGGUGGGU 171
hsamir181d
MIMAT0002821 AACAUUCAUUGUUGUCGGUGGGU 172
hsamir182
MIMAT0000259 UUUGGCAAUGGUAGAACUCACACU 173
hsamir182*
MIMAT0000260 UGGUUCUAGACUUGCCAACUA 174
hsamir183
MIMAT0000261 UAUGGCACUGGUAGAAUUCACU 175
hsamir183*
MIMAT0004560 GUGAAUUACCGAAGGGCCAUAA 176
hsamir185
MIMAT0000455 UGGAGAGAAAGGCAGUUCCUGA 177
hsamir185*
MIMAT0004611 AGGGGCUGGCUUUCCUCUGGUC 178
hsamir186
MIMAT0000456 CAAAGAAUUCUCCUUUUGGGCU 179
hsamir186*
MIMAT0004612 GCCCAAAGGUGAAUUUUUUGGG 180
hsamir190
MIMAT0000458 UGAUAUGUUUGAUAUAUUAGGU 181
hsamir191
MIMAT0000440 CAACGGAAUCCCAAAAGCAGCUG 182
hsamir191*
MIMAT0001618 GCUGCGCUUGGAUUUCGUCCCC 183
hsamir192
MIMAT0000222 CUGACCUAUGAAUUGACAGCC 184
hsamir192*
MIMAT0004543 CUGCCAAUUCCAUAGGUCACAG 185
hsamir193a3p
MIMAT0000459 AACUGGCCUACAAAGUCCCAGU 186
hsamir193a5p
MIMAT0004614 UGGGUCUUUGCGGGCGAGAUGA 187
hsamir193b
MIMAT0002819 AACUGGCCCUCAAAGUCCCGCU 188
hsamir193b*
MIMAT0004767 CGGGGUUUUGAGGGCGAGAUGA 189
hsamir195
MIMAT0000461 UAGCAGCACAGAAAUAUUGGC 190
hsamir195*
MIMAT0004615 CCAAUAUUGGCUGUGCUGCUCC 191
hsamir196a*
MIMAT0004562 CGGCAACAAGAAACUGCCUGAG 192
hsamir196a1
MIMAT0000226 UAGGUAGUUUCAUGUUGUUGGG 193
hsamir196a2
MIMAT0000226 UAGGUAGUUUCAUGUUGUUGGG 194
hsamir196b
MIMAT0001080 UAGGUAGUUUCCUGUUGUUGGG 195
hsamir197
MIMAT0000227 UUCACCACCUUCUCCACCCAGC 196
hsamir198
MIMAT0000228 GGUCCAGAGGGGAGAUAGGUUC 197
hsamir199a3p
MIMAT0000232 ACAGUAGUCUGCACAUUGGUUA 198
hsamir199a5p
MIMAT0000231 CCCAGUGUUCAGACUACCUGUUC 199
hsamir199a5p
MIMAT0000231 CCCAGUGUUCAGACUACCUGUUC 200
hsamir199b3p
MIMAT0004563 ACAGUAGUCUGCACAUUGGUUA 201
hsamir199b5p
MIMAT0000263 CCCAGUGUUUAGACUAUCUGUUC 202
hsamir200a
MIMAT0000682 UAACACUGUCUGGUAACGAUGU 203
hsamir200a*
MIMAT0001620 CAUCUUACCGGACAGUGCUGGA 204
hsamir200b
MIMAT0000318 UAAUACUGCCUGGUAAUGAUGA 205
hsamir200b*
MIMAT0004571 CAUCUUACUGGGCAGCAUUGGA 206
hsamir200c
MIMAT0000617 UAAUACUGCCGGGUAAUGAUGGA 207
hsamir200c*
MIMAT0004657 CGUCUUACCCAGCAGUGUUUGG 208
hsamir203
MIMAT0000264 GUGAAAUGUUUAGGACCACUAG 209
hsamir204
MIMAT0000265 UUCCCUUUGUCAUCCUAUGCCU 210
hsamir205
MIMAT0000266 UCCUUCAUUCCACCGGAGUCUG 211
hsamir210
MIMAT0000267 CUGUGCGUGUGACAGCGGCUGA 212
hsamir213
MIMAT0000256 AACAUUCAACGCUGUCGGUGAGU 213
hsamir214
MIMAT0000271 ACAGCAGGCACAGACAGGCAGU 214
hsamir214*
MIMAT0004564 UGCCUGUCUACACUUGCUGUGC 215
hsamir216a
MIMAT0000273 UAAUCUCAGCUGGCAACUGUGA 216
hsamir216b
MIMAT0004959 AAAUCUCUGCAGGCAAAUGUGA 217
hsamir217
MIMAT0000274 UACUGCAUCAGGAACUGAUUGGA 218
hsamir2181
MIMAT0000275 UUGUGCUUGAUCUAACCAUGU 219
hsamir2181*
MIMAT0004565 AUGGUUCCGUCAAGCACCAUGG 220
hsamir2182
MIMAT0000275 UUGUGCUUGAUCUAACCAUGU 221
hsamir2182*
MIMAT0004566 CAUGGUUCUGUCAAGCACCGCG 222
hsamir221
MIMAT0000278 AGCUACAUUGUCUGCUGGGUUUC 223
hsamir221*
MIMAT0004568 ACCUGGCAUACAAUGUAGAUUU 224
hsamir222
MIMAT0000279 AGCUACAUCUGGCUACUGGGU 225
hsamir222*
MIMAT0004569 CUCAGUAGCCAGUGUAGAUCCU 226
hsamir223
MIMAT0000280 UGUCAGUUUGUCAAAUACCCCA 227
hsamir223*
MIMAT0004570 CGUGUAUUUGACAAGCUGAGUU 228
hsamir224
MIMAT0000281 CAAGUCACUAGUGGUUCCGUU 229
hsamir302a
MIMAT0000684 UAAGUGCUUCCAUGUUUUGGUGA 230
hsamir302a*
MIMAT0000683 ACUUAAACGUGGAUGUACUUGCU 231
hsamir302b
MIMAT0000715 UAAGUGCUUCCAUGUUUUAGUAG 232
hsamir302b*
MIMAT0000714 ACUUUAACAUGGAAGUGCUUUC 233
hsamir302c
MIMAT0000717 UAAGUGCUUCCAUGUUUCAGUGG 234
hsamir302c*
MIMAT0000716 UUUAACAUGGGGGUACCUGCUG 235
hsamir302d
MIMAT0000718 UAAGUGCUUCCAUGUUUGAGUGU 236
hsamir302d*
MIMAT0004685 ACUUUAACAUGGAGGCACUUGC 237
hsamir302e
MIMAT0005931 UAAGUGCUUCCAUGCUU 238
hsamir302f
MIMAT0005932 UAAUUGCUUCCAUGUUU 239
hsamir320a
MIMAT0000510 AAAAGCUGGGUUGAGAGGGCGA 240
hsamir320b1
MIMAT0005792 AAAAGCUGGGUUGAGAGGGCAA 241
hsamir320b2
MIMAT0005792 AAAAGCUGGGUUGAGAGGGCAA 242
hsamir320c1
MIMAT0005793 AAAAGCUGGGUUGAGAGGGU 243
hsamir320c2
MIMAT0005793 AAAAGCUGGGUUGAGAGGGU 244
hsamir320d1
MIMAT0006764 AAAAGCUGGGUUGAGAGGA 245
hsamir320d2
MIMAT0006764 AAAAGCUGGGUUGAGAGGA 246
hsamir3243p
MIMAT0000762 ACUGCCCCAGGUGCUGCUGG 247
hsamir3245p
MIMAT0000761 CGCAUCCCCUAGGGCAUUGGUGU 248
hsamir326
MIMAT0000756 CCUCUGGGCCCUUCCUCCAG 249
hsamir328
MIMAT0000752 CUGGCCCUCUCUGCCCUUCCGU 250
hsamir3303p
MIMAT0000751 GCAAAGCACACGGCCUGCAGAGA 251
hsamir3305p
MIMAT0004693 UCUCUGGGCCUGUGUCUUAGGC 252
hsamir3313p
MIMAT0000760 GCCCCUGGGCCUAUCCUAGAA 253
hsamir3315p
MIMAT0004700 CUAGGUAUGGUCCCAGGGAUCC 254
hsamir335
MIMAT0000765 UCAAGAGCAAUAACGAAAAAUGU 255
hsamir335*
MIMAT0004703 UUUUUCAUUAUUGCUCCUGACC 256
hsamir3393p
MIMAT0004702 UGAGCGCCUCGACGACAGAGCCG 257
hsamir3395p
MIMAT0000764 UCCCUGUCCUCCAGGAGCUCACG 258
hsamir340
MIMAT0004692 UUAUAAAGCAAUGAGACUGAUU 259
hsamir340*
MIMAT0000750 UCCGUCUCAGUUACUUUAUAGC 260
hsamir3423p
MIMAT0000753 UCUCACACAGAAAUCGCACCCGU 261
hsamir3425p
MIMAT0004694 AGGGGUGCUAUCUGUGAUUGA 262
hsamir345
MIMAT0000772 GCUGACUCCUAGUCCAGGGCUC 263
hsamir3613p
MIMAT0004682 UCCCCCAGGUGUGAUUCUGAUUU 264
hsamir3615p
MIMAT0000703 UUAUCAGAAUCUCCAGGGGUAC 265
hsamir370
MIMAT0000722 GCCUGCUGGGGUGGAACCUGGU 266
hsamir374a
MIMAT0000727 UUAUAAUACAACCUGAUAAGUG 267
hsamir374b
MIMAT0004955 AUAUAAUACAACCUGCUAAGUG 268
hsamir376a*
MIMAT0003386 GUAGAUUCUCCUUCUAUGAGUA 269
hsamir376a1
MIMAT0000729 AUCAUAGAGGAAAAUCCACGU 270
hsamir376a2
MIMAT0000729 AUCAUAGAGGAAAAUCCACGU 271
hsamir376b
MIMAT0002172 AUCAUAGAGGAAAAUCCAUGUU 272
hsamir376c
MIMAT0000720 AACAUAGAGGAAAUUCCACGU 273
hsamir378
MIMAT0000732 ACUGGACUUGGAGUCAGAAGG 274
hsamir378*
MIMAT0000731 CUCCUGACUCCAGGUCCUGUGU 275
hsamir382
MIMAT0000737 GAAGUUGUUCGUGGUGGAUUCG 276
hsamir411
MIMAT0003329 UAGUAGACCGUAUAGCGUACG 277
hsamir411*
MIMAT0004813 UAUGUAACACGGUCCACUAACC 278
hsamir423
MIMAT0004748 UGAGGGGCAGAGAGCGAGACUUU 279
hsamir423*
MIMAT0001340 AGCUCGGUCUGAGGCCCCUCAGU 280
hsamir4253p
MIMAT0001343 AUCGGGAAUGUCGUGUCCGCCC 281
hsamir4255p
MIMAT0003393 AAUGACACGAUCACUCCCGUUGA 282
hsamir432
MIMAT0002814 UCUUGGAGUAGGUCAUUGGGUGG 283
hsamir432*
MIMAT0002815 CUGGAUGGCUCCUCCAUGUCU 284
hsamir433
MIMAT0001627 AUCAUGAUGGGCUCCUCGGUGU 285
hsamir484
MIMAT0002174 UCAGGCUCAGUCCCCUCCCGAU 286
hsamir4853p
MIMAT0002176 GUCAUACACGGCUCUCCUCUCU 287
hsamir4855p
MIMAT0002175 AGAGGCUGGCCGUGAUGAAUUC 288
hsamir4863p
MIMAT0004762 CGGGGCAGCUCAGUACAGGAU 289
hsamir4865p
MIMAT0002177 UCCUGUACUGAGCUGCCCCGAG 290
hsamir487a
MIMAT0002178 AAUCAUACAGGGACAUCCAGUU 291
hsamir487b
MIMAT0003180 AAUCGUACAGGGUCAUCCACUU 292
hsamir532
MIMAT0002888 CAUGCCUUGAGUGUAGGACCGU 293
hsamir5325p
MIMAT0004780 CCUCCCACACCCAAGGCUUGCA 294
hsamir539
MIMAT0003163 GGAGAAAUUAUCCUUGGUGUGU 295
hsamir5743p
MIMAT0003239 CACGCUCAUGCACACACCCACA 296
hsamir5745p
MIMAT0004795 UGAGUGUGUGUGUGUGAGUGUGU 297
hsamir584
MIMAT0003249 UUAUGGUUUGCCUGGGACUGAG 298
hsamir6283p
MIMAT0003297 UCUAGUAAGAGUGGCAGUCGA 299
hsamir6285p
MIMAT0004809 AUGCUGACAUAUUUACUAGAGG 300
hsamir643
MIMAT0003313 ACUUGUAUGCUAGCUCAGGUAG 301
hsamir660
MIMAT0003338 UACCCAUUGCAUAUCGGAGUUG 302
Referencias
1. BajKrzyworzeka M, Szatanek R, Weglarczyk K, Baran 7, Urbanowicz B, Branski P, Ratajczak MZ, Zembala M. 5 Tumourderived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother. 2006; 55:808818.
2. Rauch U, Bonderman D, Bohrmann B, Badimon JJ, Himber J, Riederer MA, Nemerson Y. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood. 2000; 96:170175.
3. Jungi TW, Spycher MO, Nydegger UE, Barandun S. Plateletleukocyte interaction: selective binding of 10 thrombinstimulated platelets to human monocytes, polymorphonuclear leukocytes, and related cell lines. Blood. 1986; 67:629636.
4. Lyberg T, Nakstad B, Hetland O, Boye NP. Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages. Eur Respir J. 1990; 3:6167.
5. Thiagarajan P, Le A, Benedict CR. Beta(2)glycoprotein I promotes the binding of anionic phospholipid vesicles 15 by macrophages. Arterioscler Thromb Vase Biol. 1999;19:28072811.
6. Setzer F, Oberle V, Blass M, Moller E, Russwurm S, Deigner HP, Claus RA, Bauer M, Reinhart K, Losche W. Plateletderived microvesicles induce differential gene expression in monocytic cells: a DNA microarray study. Platelets. 2006;17:571576.
7. Plasterk RH. Micro RNAs in animal development. Cell. 2006;124:877881.
20 8. Willingham AT, Gingeras TR. TUF love for "junk" DNA. Cell. 2006;125:12151220.
9. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genomewide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA. 2004; 101:97409744.

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