>CDX2|NM_001265|3'UTR
   1 CCCACCGGGTTCTGCAGCGGCAGAGCAATTCCAGGCTGAGCCATGAGGAGCGTGGACTCTGCTAGACTCCTCAGGAGAGA
  81 CCCCTCCCCTCCCACCCACAGCCATAGACCTACAGACCTGGCTCTCAGAGGAAAAATGGGAGCCAGGAGTAAGACAAGTG
 161 GGATTTGGGGCCTCAAGAAATATACTCTCCCAGATTTTTACTTTTTCCCATCTGGCTTTTTCTGCCACTGAGGAGACAGA
 241 AAGCCTCCGCTGGGCTTCATTCCGGACTGGCAGAAGCATTGCCTGGACTGACCACACCAACCAGGCCTTCATCCTCCTCC
 321 CCAGCTCTTCTCTTCCTAGATCTGCAGGCTGCACCTCTGGCTAGAGCCGAGGGGAGAGAGGGACTCAAGGGAAAGGCAAG
 401 CTTGAGGCCAAGATGGCTGCTGCCTGCTCATGGCCCTCGGAGGTCCAGCTGGGCCTCCTGCCTCCGGGCAGGCAAGGTTT
 481 ACACTGCGGAAGCCAAAGGCAGCTAAGATAGAAAGCTGGACTGACCAAAGACTGCAGAACCCCCAGGTGGCCTGCGTCTT
 561 TTTTCTCTTCCCTTCCCAGACCAGGAAAGGCTTGGCTGGTGTATGCACAGGGTGTGGTATGAGGGGGTGGTTATTGGACT
 641 CCAGGCCTGACCAGGGGGCCCGAACAGGGACTTGTTTAGAGAGCCTGTCACCAGAGCTTCTCTGGGCTGAATGTATGTCA
 721 GTGCTATAAATGCCAGAGCCAACCTGGACTTCCTGTCATTTTCACAATCTTGGGGCTGATGAAGAAGGGGGTGGGGGGAG
 801 TTTGTGTTGTTGTTGCTGCTGTTTGGGTTGTTGGTCTGTGTAACATCCAAGCCAGAGTTTTTAAAGCCTTCTGGATCCAT
 881 GGGGGGAGAAGTGATATGGTGAAGGGAAGTGGGGAGTATTTGAACACAGTTGAATTTTTTCTAAAAAGAAAAAGAGATAA
 961 ATGAGCTTTCCAGATTTCAGATTCTGTATTTATCTTCAGATTTTGTCTGCAACTATTTTTTATTTTTTAAAGAAATGAAA
1041 TATCTTCAAAAAAAAAAAAAAAAAAA

ID	Duplex structure	Position	Score	MFE
1	miRNA 3' ugAGUGG-CU------GUCGCAACUUACAa 5' ||||| || | | | ||||||| Target 5' tgTCACCAGAGCTTCTCTGGGCTGAATGTa 3'	686 - 715	155.00	-14.10
2	miRNA 3' ugaguggcUGUCGCAACUUACAa 5' ||| ||||||| | Target 5' gtatttgaACACAGTTGAATTTt 3'	916 - 938	127.00	-6.70
3	miRNA 3' ugagUGGCUGUCGCAACUUACaa 5' | :||:| :| |||| | Target 5' gagaAGTGATA-TGGTGAAGGga 3'	886 - 907	102.00	-5.50

Mutant ID	Mutant Position	Mutant Source
COSN21066118	2	COSMIC
COSN13436423	7	COSMIC
COSN30147118	19	COSMIC
COSN31502792	20	COSMIC
COSN31502785	21	COSMIC
COSN30175715	44	COSMIC
COSN30107235	51	COSMIC
COSN24979205	52	COSMIC
COSN30466845	59	COSMIC
COSN30460836	70	COSMIC
COSN23411900	85	COSMIC
COSN25743370	150	COSMIC
COSN28748262	351	COSMIC
COSN22429764	412	COSMIC
COSN8587441	423	COSMIC
COSN21919014	442	COSMIC
COSN31541005	515	COSMIC
COSN30173360	531	COSMIC
COSN25891796	594	COSMIC
COSN14668007	628	COSMIC
COSN21746661	654	COSMIC
COSN31546437	888	COSMIC
COSN22576045	934	COSMIC
COSN8587440	954	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs764455094	2	dbSNP
rs570781335	4	dbSNP
rs753318240	6	dbSNP
rs1037761396	7	dbSNP
rs1805108	10	dbSNP
rs1435069983	15	dbSNP
rs371871813	16	dbSNP
rs77050040	18	dbSNP
rs1463658680	19	dbSNP
rs1373868802	20	dbSNP
rs199607422	31	dbSNP
rs760315018	36	dbSNP
rs1340965338	39	dbSNP
rs772885631	40	dbSNP
rs376469328	44	dbSNP
rs866098096	47	dbSNP
rs200476176	48	dbSNP
rs201897709	49	dbSNP
rs768546035	50	dbSNP
rs376400533	51	dbSNP
rs527497162	52	dbSNP
rs947022084	53	dbSNP
rs1416869189	57	dbSNP
rs914745843	63	dbSNP
rs1167002669	64	dbSNP
rs1395036767	65	dbSNP
rs1381591901	66	dbSNP
rs1315542807	69	dbSNP
rs1327710342	69	dbSNP
rs1157472237	74	dbSNP
rs914339204	78	dbSNP
rs1333145704	80	dbSNP
rs764874979	81	dbSNP
rs1418968652	83	dbSNP
rs762233902	84	dbSNP
rs202146369	85	dbSNP
rs1263907374	88	dbSNP
rs1224470680	89	dbSNP
rs1474004241	90	dbSNP
rs776919419	93	dbSNP
rs975158709	95	dbSNP
rs1486601798	96	dbSNP
rs1166750425	97	dbSNP
rs532889936	104	dbSNP
rs181110828	105	dbSNP
rs543853692	113	dbSNP
rs965041018	116	dbSNP
rs910746855	123	dbSNP
rs1311752519	126	dbSNP
rs1231276644	130	dbSNP
rs1353122056	131	dbSNP
rs1416270053	137	dbSNP
rs1294251305	146	dbSNP
rs1335587900	153	dbSNP
rs985191891	163	dbSNP
rs1263076888	167	dbSNP
rs1351486707	168	dbSNP
rs1199875246	170	dbSNP
rs1338913184	171	dbSNP
rs987656794	175	dbSNP
rs1188955015	177	dbSNP
rs955131774	183	dbSNP
rs952428763	186	dbSNP
rs1382994412	189	dbSNP
rs1365402324	208	dbSNP
rs1026784903	210	dbSNP
rs575240730	212	dbSNP
rs1026534909	214	dbSNP
rs1457139521	229	dbSNP
rs1395906585	233	dbSNP
rs764642912	236	dbSNP
rs1436162255	244	dbSNP
rs528044219	245	dbSNP
rs34963801	247	dbSNP
rs1367527979	251	dbSNP
rs1013039480	261	dbSNP
rs776174542	263	dbSNP
rs1429950550	264	dbSNP
rs1234227417	265	dbSNP
rs372032016	282	dbSNP
rs1350193015	290	dbSNP
rs867525884	297	dbSNP
rs1002673154	298	dbSNP
rs1187427832	302	dbSNP
rs903110155	310	dbSNP
rs1479785541	314	dbSNP
rs1041590893	316	dbSNP
rs553610224	320	dbSNP
rs893258640	323	dbSNP
rs1211584669	332	dbSNP
rs1192977680	333	dbSNP
rs947285424	342	dbSNP
rs2481952	351	dbSNP
rs745963387	353	dbSNP
rs1173871323	356	dbSNP
rs1228368373	356	dbSNP
rs148574915	368	dbSNP
rs1295457160	369	dbSNP
rs575341095	378	dbSNP
rs923418320	388	dbSNP
rs912275329	390	dbSNP
rs988054714	395	dbSNP
rs557476981	408	dbSNP
rs933475839	409	dbSNP
rs1440775404	413	dbSNP
rs1040641023	419	dbSNP
rs919527926	423	dbSNP
rs972337322	438	dbSNP
rs537029909	439	dbSNP
rs1294967030	442	dbSNP
rs557057927	446	dbSNP
rs963614731	451	dbSNP
rs1305938688	461	dbSNP
rs1229928227	462	dbSNP
rs535528242	465	dbSNP
rs74792463	466	dbSNP
rs535381850	479	dbSNP
rs952375969	482	dbSNP
rs566282745	485	dbSNP
rs763386690	487	dbSNP
rs879793880	488	dbSNP
rs868492287	505	dbSNP
rs903046923	509	dbSNP
rs961265327	514	dbSNP
rs546398243	523	dbSNP
rs1461300345	524	dbSNP
rs1020064332	526	dbSNP
rs1011485213	529	dbSNP
rs1254338564	541	dbSNP
rs1191605771	543	dbSNP
rs1288326512	550	dbSNP
rs1360006951	555	dbSNP
rs1450988232	569	dbSNP
rs930793066	600	dbSNP
rs1384113235	601	dbSNP
rs1296634732	611	dbSNP
rs1250923714	612	dbSNP
rs1318332727	622	dbSNP
rs1232380767	623	dbSNP
rs867273391	624	dbSNP
rs1039349159	627	dbSNP
rs1011622372	630	dbSNP
rs1240977631	631	dbSNP
rs1484633789	634	dbSNP
rs1263375831	645	dbSNP
rs1474685583	652	dbSNP
rs1186202852	653	dbSNP
rs1341709302	657	dbSNP
rs1462399081	658	dbSNP
rs942347891	659	dbSNP
rs890884325	661	dbSNP
rs1050842215	662	dbSNP
rs1289526623	670	dbSNP
rs1305739628	674	dbSNP
rs1434887697	675	dbSNP
rs771112535	688	dbSNP
rs568090881	706	dbSNP
rs372711876	707	dbSNP
rs533193625	714	dbSNP
rs1228792741	717	dbSNP
rs570448989	722	dbSNP
rs1283543324	725	dbSNP
rs1368311836	728	dbSNP
rs1167497836	737	dbSNP
rs1217241278	747	dbSNP
rs550676496	765	dbSNP
rs972223925	772	dbSNP
rs1485120014	773	dbSNP
rs1208335269	774	dbSNP
rs942261866	786	dbSNP
rs1473363821	787	dbSNP
rs1177133859	788	dbSNP
rs1406342091	789	dbSNP
rs1396310143	790	dbSNP
rs530409030	793	dbSNP
rs1159275218	795	dbSNP
rs367846281	799	dbSNP
rs867167258	799	dbSNP
rs1433054890	802	dbSNP
rs1315062597	806	dbSNP
rs561680882	807	dbSNP
rs552977017	812	dbSNP
rs1371031754	819	dbSNP
rs1225428041	821	dbSNP
rs1183706162	830	dbSNP
rs1309319223	831	dbSNP
rs1049299857	846	dbSNP
rs1346589307	851	dbSNP
rs780886884	854	dbSNP
rs1282102747	855	dbSNP
rs1250812751	856	dbSNP
rs1442648010	858	dbSNP
rs1204194801	860	dbSNP
rs931005627	863	dbSNP
rs1204632632	867	dbSNP
rs1036079961	876	dbSNP
rs754831789	879	dbSNP
rs542497316	882	dbSNP
rs972523480	886	dbSNP
rs752649679	891	dbSNP
rs1280709325	896	dbSNP
rs535355286	903	dbSNP
rs1327897277	916	dbSNP
rs967429541	934	dbSNP
rs571085867	947	dbSNP
rs1020116336	949	dbSNP
rs1448880543	958	dbSNP
rs369037226	965	dbSNP
rs928491608	967	dbSNP
rs1011327148	970	dbSNP
rs981305747	994	dbSNP
rs969876742	999	dbSNP
rs528806201	1000	dbSNP
rs1022910958	1007	dbSNP
rs1271283121	1010	dbSNP
rs990052457	1013	dbSNP
rs1348952660	1026	dbSNP
rs957405191	1040	dbSNP
rs1467529446	1043	dbSNP
rs1195530418	1047	dbSNP
rs1414975745	1060	dbSNP
rs1475192528	1068	dbSNP
rs560132224	1075	dbSNP
rs1417112952	1076	dbSNP
rs957293828	1077	dbSNP
rs1018163426	1079	dbSNP
rs1171131343	1092	dbSNP
rs1393569400	1101	dbSNP
rs1032064862	1103	dbSNP
rs1331599265	1130	dbSNP
rs546080918	1145	dbSNP
rs890820234	1151	dbSNP
rs1051193549	1152	dbSNP
rs1385579636	1154	dbSNP
rs993956816	1154	dbSNP
rs998950186	1157	dbSNP
rs1341901604	1160	dbSNP
rs532905596	1162	dbSNP
rs1471579371	1163	dbSNP
rs1410895375	1167	dbSNP
rs563853684	1168	dbSNP
rs1007723774	1170	dbSNP
rs746899067	1180	dbSNP
rs909481076	1186	dbSNP
rs1475643395	1191	dbSNP
rs1056071664	1193	dbSNP
rs1478279557	1200	dbSNP
rs937575114	1201	dbSNP
rs1208102351	1206	dbSNP
rs928688698	1225	dbSNP
rs1416933994	1226	dbSNP
rs1382497403	1242	dbSNP
rs577396225	1244	dbSNP
rs1164981418	1245	dbSNP
rs1390808898	1249	dbSNP
rs967439337	1256	dbSNP
rs930869052	1266	dbSNP
rs1315613165	1267	dbSNP
rs557159640	1270	dbSNP
rs1341923284	1273	dbSNP
rs898178484	1273	dbSNP
rs1293033301	1282	dbSNP
rs1207359311	1287	dbSNP
rs1247615884	1288	dbSNP
rs56281511	1297	dbSNP
rs913287518	1305	dbSNP
rs1327739859	1307	dbSNP
rs1409421317	1311	dbSNP
rs989955631	1327	dbSNP
rs1286459622	1329	dbSNP
rs1288081796	1335	dbSNP
rs1488715645	1337	dbSNP
rs543913501	1338	dbSNP
rs1356963167	1339	dbSNP
rs957179799	1339	dbSNP
rs1474136089	1354	dbSNP
rs1189523613	1356	dbSNP
rs1018505935	1362	dbSNP
rs1446846190	1367	dbSNP
rs574464336	1373	dbSNP
rs955468899	1374	dbSNP
rs1361948509	1377	dbSNP
rs1029333140	1379	dbSNP
rs1419909496	1386	dbSNP
rs554545819	1398	dbSNP
rs1374027119	1400	dbSNP
rs1398085053	1403	dbSNP
rs757837437	1404	dbSNP
rs1335637559	1408	dbSNP
rs993798260	1409	dbSNP
rs75162685	1410	dbSNP
rs202054630	1416	dbSNP
rs80106665	1417	dbSNP
rs11291875	1418	dbSNP
rs1491268618	1418	dbSNP
rs398022085	1418	dbSNP
rs553278211	1418	dbSNP
rs948563373	1419	dbSNP
rs200320749	1426	dbSNP
rs915717311	1426	dbSNP
rs773333487	1427	dbSNP
rs1165357247	1432	dbSNP
rs1462878168	1441	dbSNP
rs539233007	1450	dbSNP
rs887978651	1464	dbSNP
rs1392815733	1480	dbSNP
rs1180276179	1482	dbSNP
rs1467281554	1490	dbSNP
rs79038588	1491	dbSNP
rs756911075	1492	dbSNP
rs928843952	1494	dbSNP
rs1390144040	1497	dbSNP
rs1031677915	1504	dbSNP
rs1045740487	1506	dbSNP
rs946023387	1507	dbSNP
rs1268116443	1511	dbSNP
rs1234277677	1512	dbSNP
rs977861642	1513	dbSNP
rs966071659	1518	dbSNP
rs1196673543	1522	dbSNP
rs375928833	1527	dbSNP
rs544066586	1541	dbSNP
rs865830713	1545	dbSNP
rs1192409111	1548	dbSNP
rs1250635049	1551	dbSNP
rs550367583	1556	dbSNP
rs7998720	1557	dbSNP
rs1432328116	1558	dbSNP
rs372027408	1559	dbSNP
rs898038858	1559	dbSNP
rs1369883413	1572	dbSNP
rs1387554568	1591	dbSNP
rs911096270	1595	dbSNP
rs548313473	1597	dbSNP
rs955326177	1603	dbSNP
rs1029964920	1613	dbSNP
rs1216512686	1621	dbSNP
rs972408896	1622	dbSNP
rs1347850065	1623	dbSNP
rs761149655	1625	dbSNP
rs6491242	1633	dbSNP
rs112550530	1634	dbSNP
rs1191403585	1636	dbSNP
rs1260518821	1641	dbSNP
rs1170551299	1642	dbSNP
rs1476643222	1643	dbSNP
rs546510485	1644	dbSNP
rs1247496628	1648	dbSNP
rs1194748815	1652	dbSNP
rs1163476961	1655	dbSNP
rs1351683769	1656	dbSNP
rs1489768842	1657	dbSNP
rs915748638	1658	dbSNP
rs1034528038	1666	dbSNP
rs188192806	1673	dbSNP
rs1002078151	1680	dbSNP
rs1245309557	1680	dbSNP
rs1402118269	1683	dbSNP
rs1279827219	1684	dbSNP
rs1232587310	1686	dbSNP
rs1340952467	1686	dbSNP
rs1054253911	1691	dbSNP
rs1221353456	1693	dbSNP
rs1323434071	1694	dbSNP
rs370208882	1696	dbSNP
rs924564605	1700	dbSNP
rs907466834	1704	dbSNP
rs1487080528	1705	dbSNP
rs1276412090	1707	dbSNP
rs149396092	1709	dbSNP
rs977350075	1710	dbSNP
rs1045938362	1715	dbSNP
rs946284076	1719	dbSNP
rs1442958708	1724	dbSNP
rs1365454108	1726	dbSNP
rs1421731963	1727	dbSNP
rs1299092112	1735	dbSNP
rs911866354	1737	dbSNP
rs745622293	1742	dbSNP
rs1413864685	1751	dbSNP
rs986197778	1760	dbSNP
rs1442732976	1766	dbSNP
rs1355332857	1769	dbSNP
rs1310017971	1771	dbSNP
rs563930677	1772	dbSNP
rs1027787265	1776	dbSNP
rs1350925981	1779	dbSNP
rs1241866342	1781	dbSNP
rs1054378401	1789	dbSNP
rs1015620113	1790	dbSNP
rs1003768321	1791	dbSNP
rs1483849505	1797	dbSNP
rs936101992	1804	dbSNP
rs911262071	1809	dbSNP
rs1045384428	1813	dbSNP
rs778685339	1833	dbSNP
rs1441693518	1835	dbSNP
rs759687592	1836	dbSNP
rs933794612	1842	dbSNP
rs894261128	1845	dbSNP
rs559560780	1848	dbSNP
rs1412999680	1852	dbSNP
rs1173647993	1853	dbSNP
rs1360723671	1866	dbSNP
rs1448640982	1869	dbSNP
rs1054211685	1876	dbSNP
rs1374579798	1878	dbSNP
rs1190969697	1881	dbSNP
rs1481124066	1882	dbSNP
rs1254430393	1887	dbSNP
rs1448276444	1888	dbSNP
rs1309382323	1889	dbSNP
rs1346661665	1894	dbSNP
rs922440884	1894	dbSNP
rs1217161126	1896	dbSNP
rs1202525872	1899	dbSNP
rs972671595	1901	dbSNP
rs1281145414	1902	dbSNP
rs1482540935	1911	dbSNP
rs1280378487	1912	dbSNP
rs961274987	1924	dbSNP
rs543504608	1926	dbSNP
rs1459488268	1927	dbSNP
rs924456735	1935	dbSNP
rs1016647201	1939	dbSNP
rs1193191933	1941	dbSNP
rs113672795	1943	dbSNP
rs1426989860	1951	dbSNP
rs983749897	1956	dbSNP
rs1169713443	1963	dbSNP
rs1310355324	1965	dbSNP
rs959161857	1969	dbSNP
rs911895969	1970	dbSNP
rs1331403422	1976	dbSNP
rs1369678035	1984	dbSNP
rs1033820068	1990	dbSNP
rs1276320273	1992	dbSNP
rs1464740181	1995	dbSNP
rs1367868588	1998	dbSNP
rs1375182813	1999	dbSNP
rs1001730699	2001	dbSNP
rs1256579791	2004	dbSNP
rs1320566907	2007	dbSNP
rs907388230	2012	dbSNP
rs1199866720	2014	dbSNP
rs1272602175	2016	dbSNP
rs1286254803	2022	dbSNP
rs1024416494	2023	dbSNP
rs953372127	2026	dbSNP
rs1408192063	2027	dbSNP
rs920701765	2028	dbSNP
rs1421265994	2032	dbSNP
rs973498950	2035	dbSNP
rs1171372551	2040	dbSNP
rs1389386557	2044	dbSNP
rs574601056	2046	dbSNP
rs962536037	2054	dbSNP
rs1324967880	2056	dbSNP
rs111795961	2058	dbSNP
rs1399043185	2060	dbSNP
rs1276663618	2061	dbSNP
rs183509007	2064	dbSNP
rs9579136	2065	dbSNP
rs1011030964	2068	dbSNP
rs1293284444	2068	dbSNP
rs1354878524	2075	dbSNP
rs1023884092	2077	dbSNP
rs1290719855	2081	dbSNP
rs1467704502	2087	dbSNP
rs1446608600	2089	dbSNP
rs1054392907	2090	dbSNP
rs894130014	2097	dbSNP
rs1175903287	2102	dbSNP
rs1194126147	2103	dbSNP
rs113499296	2105	dbSNP
rs1033205695	2108	dbSNP
rs999922281	2112	dbSNP
rs1164446602	2119	dbSNP
rs893523527	2119	dbSNP
rs1418692619	2121	dbSNP
rs935971864	2127	dbSNP
rs889895956	2138	dbSNP
rs572132648	2140	dbSNP
rs1257859223	2143	dbSNP
rs1400920114	2150	dbSNP
rs1333949274	2151	dbSNP
rs934074750	2153	dbSNP
rs922461290	2154	dbSNP
rs1201670149	2155	dbSNP
rs972557012	2159	dbSNP
rs1254917754	2160	dbSNP
rs1238245549	2161	dbSNP
rs866598667	2167	dbSNP
rs890407320	2171	dbSNP
rs1217005400	2183	dbSNP
rs1255248970	2188	dbSNP
rs1050286499	2192	dbSNP
rs1189596806	2197	dbSNP

- Hepatology (Baltimore, Md.), 2009

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate gene expression with functional links to tumorigenesis. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and it is heterogeneous in clinical outcomes and biological activities. Recently, we have identified a subset of highly invasive epithelial cell adhesion molecule (EpCAM)(+) HCC cells from alpha-fetoprotein (AFP)(+) tumors with cancer stem/progenitor cell features, that is, the abilities to self-renew, differentiate, and initiate aggressive tumors in vivo. Here, using a global microarray-based miRNA profiling approach followed by validation with quantitative reverse transcription polymerase chain reaction, we have demonstrated that conserved miR-181 family members were up-regulated in EpCAM(+)AFP(+) HCCs and in EpCAM(+) HCC cells isolated from AFP(+) tumors. Moreover, miR-181 family members were highly expressed in embryonic livers and in isolated hepatic stem cells. Importantly, inhibition of miR-181 led to a reduction in EpCAM(+) HCC cell quantity and tumor initiating ability, whereas exogenous miR-181 expression in HCC cells resulted in an enrichment of EpCAM(+) HCC cells. We have found that miR-181 could directly target hepatic transcriptional regulators of differentiation (for example, caudal type homeobox transcription factor 2 [CDX2] and GATA binding protein 6 [GATA6]) and an inhibitor of Wnt/beta-catenin signaling (nemo-like kinase [NLK]). Taken together, our results define a novel regulatory link between miR-181s and human EpCAM(+) liver cancer stem/progenitor cells and imply that molecular targeting of miR-181 may eradicate HCC.