>Fgfr2|NM_001109892|3'UTR
   1 GCGGGTGTGTCTTCCTGTCCCCAAACAGGACAGCACCAGGAACCTACTTACACTGAGCAGAGAGGCTGTGCCCCCAAAGC
  81 GTGTGGCATGCCTCCACATGTATATATGGATCAGAGGAGTAAATAGTGGGAAGAGTATTTGTCACGTGTGTGAAGATTTA
 161 TACAGTTGGAAACATGTTACTTTCCCAGGAAAGGAAGACTGTTTCCTGATAAGTGGACAGCCGCAAGCCACCGCCACCCT
 241 CTCTGACCTACCATGTATGCTGGCTGTGCCCCAGTTGGACTCAAGGCAGACCGCTGTTCTGCCTTCCTTGTTAATTTTGT
 321 AATAATTGGAGAAGATATATGTCAGCACATACTTACAGAGCACAAATGCAGTATATAGGTGCTGGATGTATGTAAATATA
 401 TTCAAATTATGTATAAATATATATTATATATTTACAAGGAATTATTTTTTGTATTGATCTTAAATGGATGTCCTGATGCA
 481 CCTAGAAAATTGGTCTCTCCATTTTTTTTAAATAGATATTTGCTAAATGCTGTTCTTAGAATTTCTTAATTTTCACCGAG
 561 CAGAGGTGGGAAAATACTTTTGCTTTCAGGGAAAATGGTGTCACATTAATTTATTAATGAATTGGTAATATACGAAACAA
 641 TTAATCATCTATAGTTTGTTTTTTTTTTGTAATTTAAGTGGCATTTCTATGCAGACAGCACAGAGGACTAGTTAATCTAT
 721 TGCTTGGACTTAACTGGTTATTGGATCCTTTGAGAAGAGAAATATTTACGATATATGACTAATTTGGGGGGAAATGATGT
 801 CTTGATTTATTTGTGTTTCAACTCTGCTGTCCGATGATTATGTCTAAACACCTCAATGCCCACCTTTCAAGAAACCTTTT
 881 AAACTCTGTCACCCCAGTGTAATAATTAACCAGACTTCCCATGACAAATGGTACCAGAGTCCTCATCCCAAGATGCCTTA
 961 ATCCTCTTCTCTGGAGAACAGACTCCCATCGGAGACGGCAGGGTGGGTCTTGTCTGGCAGCTGGCCTTCTGCCTGAGTTA
1041 CACACCCGTCACATTCGCCTTGCTCCCTCTCCGTGAGTTTTGATAACAGCTTCAGATTCTTCAGCATCAAAAACTCTTTG
1121 GGGACTCTCCATCCTCTCGGAGAATAGTGAAAGCCCAGGGTTATTCTGTCGAGAGTTTGGGACCTCCTTCCATCTTCTGC
1201 AGGGTTTGCTTCTGGCTTCCACCCACTTCTGACAAGACCTCTCCTCACTAAAAGATCTGGCCCGAGAGCTACACCCGACA
1281 AGAGAACGCTTACCATTGATTTCCGTGTTCAAGTCTTGTGCTTTGCTTTGGACACGCCCACTCACCTTGCTACCGTCATG
1361 TGACAGGAGTGCAGACTACACTGATTTTATGTGTTTTGAAATTGGAGAAAGTATTTAATAAAACCTGTTAATTTTTATAC
1441 TGACAATAAAAATGTTTCTACAGATATTAATGTTAACGAGACAAAAATAAATGTCGCGCAGCTTATTTTTTTAAAAAAAA
1521 AAAAAAAAAAAAAAAAAAA

ID	Duplex structure	Position	Score	MFE
1	miRNA 3' cuccaaagggcacaUACAAAGu 5' ||||||| Target 5' tactgacaataaaaATGTTTCt 3'	1438 - 1459	140.00	-5.20
2	miRNA 3' cuCCAAAGGGC-----ACAUACAAAGu 5' | | ||::| | |:|||||| Target 5' atGATGTCTTGATTTATTTGTGTTTCa 3'	794 - 820	136.00	-9.10
3	miRNA 3' cuccaaagggcacauACAAAGu 5' |||||| Target 5' ccaggaaaggaagacTGTTTCc 3'	185 - 206	120.00	-5.90

- Circulation, 2010

BACKGROUND: MicroRNAs (miRs) participate in many cardiac pathophysiological processes, including ischemia/reperfusion (I/R)-induced cardiac injury. Recently, we and others observed that miR-494 was downregulated in murine I/R-injured and human infarcted hearts. However, the functional consequence of miR-494 in response to I/R remains unknown. METHODS AND RESULTS: We generated a mouse model with cardiac-specific overexpression of miR-494. Transgenic hearts and wild-type hearts from multiple lines were subjected to global no-flow I/R with the Langendorff system. Transgenic hearts exhibited improved recovery of contractile performance over the reperfusion period. This improvement was accompanied by remarkable decreases in both lactate dehydrogenase release and the extent of apoptosis in transgenic hearts compared with wild-type hearts. In addition, myocardial infarction size was significantly reduced in transgenic hearts on I/R in vivo compared with wild-type hearts. Similarly, short-term overexpression of miR-494 in cultured adult cardiomyocytes demonstrated an inhibition of caspase-3 activity and reduced cell death on simulated I/R. In vivo treatment with antisense oligonucleotide miR-494 increased I/R-triggered cardiac injury relative to the administration of mutant antisense oligonucleotide miR-494 and saline controls. We further identified that 3 proapoptotic proteins (PTEN, ROCK1, and CaMKIIdelta) and 2 antiapoptotic proteins (FGFR2 and LIF) were authentic targets for miR-494. Importantly, the Akt-mitochondrial signaling pathway was activated in miR-494-overexpressing myocytes. CONCLUSIONS: Our findings suggest that although miR-494 targets both proapoptotic and antiapoptotic proteins, the ultimate consequence is activation of the Akt pathway, leading to cardioprotective effects against I/R-induced injury. Thus, miR-494 may constitute a new therapeutic agent for the treatment of ischemic heart disease.