ID	Duplex structure	Position	Score	MFE
1	miRNA 3' gaugCGCAU-AAGAAUUCGUUAUu 5' || |: ||||| ||||||| Target 5' atggGCCTGCTTCTT-AGCAATAt 3'	1815 - 1837	162.00	-11.20
2	miRNA 3' gaUGCGCA----UAAGAA--UUCGUUAUu 5' || :|| ||| | |||||||| Target 5' gtACCTGTTCAGATTAATCAAAGCAATAg 3'	193 - 221	153.00	-9.40
3	miRNA 3' gaUGCGCAUAAGAAUUCGUUAUu 5' | |:|||||: | |||| || Target 5' gcAAGTGTATTTATTAGCATTAa 3'	698 - 720	141.00	-10.50

Mutant ID	Mutant Position	Mutant Source
COSN22236929	34	COSMIC
COSN28185962	63	COSMIC
COSN30115771	86	COSMIC
COSN30483590	111	COSMIC
COSN1798689	190	COSMIC
COSN20225597	326	COSMIC
COSN26601907	341	COSMIC
COSN21449735	352	COSMIC
COSN6197626	399	COSMIC
COSN28018181	414	COSMIC
COSN6197627	448	COSMIC
COSN27837789	452	COSMIC
COSN1798691	489	COSMIC
COSN26538150	742	COSMIC
COSN19658912	891	COSMIC
COSN28733054	958	COSMIC
COSN31551319	1003	COSMIC
COSN30543529	1174	COSMIC
COSN31547740	1206	COSMIC
COSN23356980	1481	COSMIC
COSN1798693	1490	COSMIC
COSN31556212	1542	COSMIC
COSN31518888	1860	COSMIC

Mutant ID	Mutant Position	Mutant Source
rs774892480	2	dbSNP
rs753100790	4	dbSNP
rs186657614	5	dbSNP
rs890541271	12	dbSNP
rs1272951224	13	dbSNP
rs943162132	15	dbSNP
rs1354437183	16	dbSNP
rs778257804	18	dbSNP
rs1374802774	19	dbSNP
rs760009660	20	dbSNP
rs1359520298	24	dbSNP
rs1446551182	26	dbSNP
rs1038899649	28	dbSNP
rs1191402765	29	dbSNP
rs367975208	31	dbSNP
rs1475499519	32	dbSNP
rs1186892872	33	dbSNP
rs771272626	35	dbSNP
rs201665827	36	dbSNP
rs772480143	36	dbSNP
rs1454988791	37	dbSNP
rs1158824586	38	dbSNP
rs779210090	39	dbSNP
rs979978063	44	dbSNP
rs564160733	48	dbSNP
rs1296879140	49	dbSNP
rs749879179	55	dbSNP
rs1421987574	59	dbSNP
rs1216493959	63	dbSNP
rs745717981	67	dbSNP
rs561390637	70	dbSNP
rs1486012655	71	dbSNP
rs572201418	91	dbSNP
rs938111040	96	dbSNP
rs1000138449	99	dbSNP
rs1031326059	100	dbSNP
rs192688512	110	dbSNP
rs891441569	112	dbSNP
rs1261672417	113	dbSNP
rs1185206401	115	dbSNP
rs945404246	120	dbSNP
rs1385593706	125	dbSNP
rs1013949675	128	dbSNP
rs1315378852	130	dbSNP
rs1024023290	132	dbSNP
rs1339189463	133	dbSNP
rs530340425	133	dbSNP
rs12693429	134	dbSNP
rs1002776856	140	dbSNP
rs1156440726	150	dbSNP
rs1409581442	152	dbSNP
rs1033893065	155	dbSNP
rs904121275	158	dbSNP
rs1456374963	162	dbSNP
rs1370144544	165	dbSNP
rs1188120861	166	dbSNP
rs1400775242	167	dbSNP
rs1475580413	167	dbSNP
rs1262550296	175	dbSNP
rs1191856807	183	dbSNP
rs60853545	188	dbSNP
rs1262927765	195	dbSNP
rs1209636983	197	dbSNP
rs535773355	201	dbSNP
rs1354634912	203	dbSNP
rs1357940030	208	dbSNP
rs1234372585	212	dbSNP
rs1049911125	216	dbSNP
rs1275755561	219	dbSNP
rs889946479	220	dbSNP
rs1326635228	222	dbSNP
rs1322411140	226	dbSNP
rs973655561	228	dbSNP
rs919528398	231	dbSNP
rs1007973960	234	dbSNP
rs1465033502	235	dbSNP
rs1423055401	239	dbSNP
rs950681100	252	dbSNP
rs1376560263	253	dbSNP
rs1019327452	254	dbSNP
rs1281459213	256	dbSNP
rs765112824	259	dbSNP
rs555349661	263	dbSNP
rs1351571600	274	dbSNP
rs987439446	277	dbSNP
rs1457689901	278	dbSNP
rs1255665070	282	dbSNP
rs1218735266	288	dbSNP
rs896865716	289	dbSNP
rs1273887814	291	dbSNP
rs73016134	296	dbSNP
rs775327514	298	dbSNP
rs1332678147	302	dbSNP
rs943503866	303	dbSNP
rs1039260048	308	dbSNP
rs75425753	324	dbSNP
rs1398052698	328	dbSNP
rs952684681	337	dbSNP
rs935844630	343	dbSNP
rs1205434294	344	dbSNP
rs1243582440	346	dbSNP
rs1457133704	349	dbSNP
rs1176470633	354	dbSNP
rs138109208	362	dbSNP
rs891721139	363	dbSNP
rs1236918578	365	dbSNP
rs1470273278	371	dbSNP
rs1437919326	373	dbSNP
rs375280649	376	dbSNP
rs1171486452	380	dbSNP
rs1013896259	381	dbSNP
rs1346655687	383	dbSNP
rs76751361	386	dbSNP
rs1471254215	388	dbSNP
rs992625987	389	dbSNP
rs1374292954	391	dbSNP
rs768653192	393	dbSNP
rs1001316409	397	dbSNP
rs918017841	398	dbSNP
rs967172205	399	dbSNP
rs978140117	400	dbSNP
rs1177758575	404	dbSNP
rs1333559818	406	dbSNP
rs1413032683	424	dbSNP
rs1377529509	425	dbSNP
rs1174455735	429	dbSNP
rs1400076474	445	dbSNP
rs1378793435	451	dbSNP
rs1445011969	455	dbSNP
rs543463253	460	dbSNP
rs1331227739	463	dbSNP
rs1034251660	465	dbSNP
rs963553604	469	dbSNP
rs563239839	472	dbSNP
rs936970159	482	dbSNP
rs143988439	489	dbSNP
rs543353023	490	dbSNP
rs911437605	497	dbSNP
rs1026490266	498	dbSNP
rs951001226	502	dbSNP
rs865939012	505	dbSNP
rs1287884945	506	dbSNP
rs575668394	508	dbSNP
rs562353777	510	dbSNP
rs1282312432	524	dbSNP
rs987428010	525	dbSNP
rs1357374126	531	dbSNP
rs1041168798	533	dbSNP
rs1419316511	535	dbSNP
rs774425480	540	dbSNP
rs1401597970	547	dbSNP
rs1413740720	551	dbSNP
rs775636618	552	dbSNP
rs148252753	556	dbSNP
rs1257582865	557	dbSNP
rs1048088603	568	dbSNP
rs974824811	574	dbSNP
rs926050172	578	dbSNP
rs1265127763	580	dbSNP
rs762143325	581	dbSNP
rs1065266	585	dbSNP
rs1287650489	588	dbSNP
rs1337121331	590	dbSNP
rs913147255	590	dbSNP
rs75998872	592	dbSNP
rs1399678552	595	dbSNP
rs1197659358	596	dbSNP
rs1045407273	600	dbSNP
rs1034274463	605	dbSNP
rs532241497	606	dbSNP
rs905557597	607	dbSNP
rs773565416	617	dbSNP
rs1038083360	621	dbSNP
rs1322207135	625	dbSNP
rs761162056	632	dbSNP
rs766745356	635	dbSNP
rs1170040857	638	dbSNP
rs1169319086	641	dbSNP
rs1476528814	642	dbSNP
rs1014113447	644	dbSNP
rs1186683776	645	dbSNP
rs1488043155	648	dbSNP
rs1244752222	650	dbSNP
rs1215557046	653	dbSNP
rs571432682	654	dbSNP
rs1405044360	655	dbSNP
rs1321796582	659	dbSNP
rs1257288867	662	dbSNP
rs1218124887	664	dbSNP
rs1316071392	669	dbSNP
rs1020109128	681	dbSNP
rs1215366224	686	dbSNP
rs1367421663	697	dbSNP
rs185045831	699	dbSNP
rs1395886000	700	dbSNP
rs754325842	708	dbSNP
rs978571124	710	dbSNP
rs1355719505	711	dbSNP
rs1170780797	712	dbSNP
rs925348722	715	dbSNP
rs1422851018	720	dbSNP
rs528020140	721	dbSNP
rs1277578438	727	dbSNP
rs1454519147	730	dbSNP
rs994957950	731	dbSNP
rs1196615692	735	dbSNP
rs911488562	742	dbSNP
rs944271161	745	dbSNP
rs1205536317	750	dbSNP
rs1041221606	757	dbSNP
rs1301468003	759	dbSNP
rs760047093	760	dbSNP
rs1271736007	761	dbSNP
rs1237002053	762	dbSNP
rs1372103532	764	dbSNP
rs918738204	769	dbSNP
rs1026478956	773	dbSNP
rs1374970197	774	dbSNP
rs1339802422	775	dbSNP
rs1465279613	777	dbSNP
rs929776418	786	dbSNP
rs1048620832	787	dbSNP
rs886672612	794	dbSNP
rs888168852	795	dbSNP
rs1009130536	797	dbSNP
rs1176768306	799	dbSNP
rs1019625797	800	dbSNP
rs964716805	802	dbSNP
rs975152748	803	dbSNP
rs1177874711	809	dbSNP
rs764038898	816	dbSNP
rs755337857	817	dbSNP
rs530881370	821	dbSNP
rs1477142318	824	dbSNP
rs188311898	826	dbSNP
rs1195930046	827	dbSNP
rs1014165828	828	dbSNP
rs1374036296	834	dbSNP
rs756754521	837	dbSNP
rs957478140	850	dbSNP
rs1020148517	853	dbSNP
rs967612099	855	dbSNP
rs1367692270	859	dbSNP
rs1314391193	868	dbSNP
rs988641005	870	dbSNP
rs1359705292	874	dbSNP
rs1425461611	879	dbSNP
rs1156587443	883	dbSNP
rs999996672	886	dbSNP
rs1364345467	890	dbSNP
rs1163907585	891	dbSNP
rs765242532	891	dbSNP
rs1255476421	894	dbSNP
rs1190425593	898	dbSNP
rs1032849566	901	dbSNP
rs10645049	901	dbSNP
rs1261834692	901	dbSNP
rs1353201034	901	dbSNP
rs1358645587	904	dbSNP
rs763515214	905	dbSNP
rs1294560516	911	dbSNP
rs1297594669	919	dbSNP
rs1326873927	922	dbSNP
rs376654739	923	dbSNP
rs751012615	926	dbSNP
rs985445518	927	dbSNP
rs1315737856	928	dbSNP
rs528182429	937	dbSNP
rs1383713455	939	dbSNP
rs555671268	945	dbSNP
rs1018213386	946	dbSNP
rs1415828207	950	dbSNP
rs1456325045	950	dbSNP
rs565792151	950	dbSNP
rs981353544	952	dbSNP
rs927204969	953	dbSNP
rs2463	958	dbSNP
rs918807070	962	dbSNP
rs1434428922	963	dbSNP
rs1449151282	966	dbSNP
rs930144379	974	dbSNP
rs1284752933	975	dbSNP
rs780885741	976	dbSNP
rs984276072	982	dbSNP
rs909641676	984	dbSNP
rs1316677604	991	dbSNP
rs1268061738	993	dbSNP
rs937054188	996	dbSNP
rs1326875160	997	dbSNP
rs1300300617	1000	dbSNP
rs1055495853	1004	dbSNP
rs1491447023	1006	dbSNP
rs895473972	1006	dbSNP
rs1491335581	1007	dbSNP
rs557955405	1009	dbSNP
rs547365295	1011	dbSNP
rs1038478361	1019	dbSNP
rs750042692	1020	dbSNP
rs1042031292	1022	dbSNP
rs1476493441	1027	dbSNP
rs1374042343	1028	dbSNP
rs1198623994	1029	dbSNP
rs1452916869	1033	dbSNP
rs1255445657	1034	dbSNP
rs903068753	1038	dbSNP
rs577827156	1039	dbSNP
rs929749727	1042	dbSNP
rs1047869954	1044	dbSNP
rs1158248501	1046	dbSNP
rs1339637439	1047	dbSNP
rs1032823676	1056	dbSNP
rs886579493	1057	dbSNP
rs1455407367	1059	dbSNP
rs1231851413	1070	dbSNP
rs1372832182	1074	dbSNP
rs1304140721	1086	dbSNP
rs142742974	1088	dbSNP
rs748423218	1090	dbSNP
rs1385586730	1092	dbSNP
rs1019155807	1095	dbSNP
rs1326910757	1108	dbSNP
rs867416149	1109	dbSNP
rs965346559	1111	dbSNP
rs1395344183	1114	dbSNP
rs1433263576	1119	dbSNP
rs1334473113	1121	dbSNP
rs1194876308	1123	dbSNP
rs976745837	1123	dbSNP
rs900760447	1126	dbSNP
rs1183388801	1128	dbSNP
rs951638163	1130	dbSNP
rs996186344	1132	dbSNP
rs1255056887	1135	dbSNP
rs755949521	1152	dbSNP
rs193181602	1156	dbSNP
rs957424084	1159	dbSNP
rs1349865639	1162	dbSNP
rs988922955	1163	dbSNP
rs937106490	1173	dbSNP
rs573623081	1188	dbSNP
rs971197797	1192	dbSNP
rs184613602	1195	dbSNP
rs147385599	1197	dbSNP
rs1336363308	1198	dbSNP
rs916961338	1200	dbSNP
rs1413164383	1203	dbSNP
rs927223628	1206	dbSNP
rs903118453	1208	dbSNP
rs1406470224	1209	dbSNP
rs935915684	1211	dbSNP
rs1470213851	1212	dbSNP
rs1256183862	1216	dbSNP
rs937295364	1219	dbSNP
rs1257719755	1231	dbSNP
rs1215668903	1232	dbSNP
rs1444997768	1233	dbSNP
rs888941411	1236	dbSNP
rs1224261953	1263	dbSNP
rs1351582606	1269	dbSNP
rs560783570	1271	dbSNP
rs1292717044	1276	dbSNP
rs1231742032	1285	dbSNP
rs973745939	1291	dbSNP
rs1245406628	1295	dbSNP
rs139450099	1296	dbSNP
rs545214141	1300	dbSNP
rs1178330733	1319	dbSNP
rs1248670969	1322	dbSNP
rs1430469787	1328	dbSNP
rs1343747566	1329	dbSNP
rs1320926273	1339	dbSNP
rs1421045887	1341	dbSNP
rs1159966439	1342	dbSNP
rs1018321343	1343	dbSNP
rs549731268	1346	dbSNP
rs929655059	1347	dbSNP
rs1162193985	1348	dbSNP
rs1475878778	1353	dbSNP
rs1377092317	1357	dbSNP
rs1046774863	1359	dbSNP
rs890876564	1370	dbSNP
rs1174145111	1371	dbSNP
rs1243631482	1373	dbSNP
rs567641775	1375	dbSNP
rs1216462325	1377	dbSNP
rs944844081	1386	dbSNP
rs868168358	1392	dbSNP
rs900753328	1399	dbSNP
rs565174754	1400	dbSNP
rs901236555	1401	dbSNP
rs1360357855	1408	dbSNP
rs1054448020	1412	dbSNP
rs1431867025	1413	dbSNP
rs998610875	1416	dbSNP
rs1324387347	1429	dbSNP
rs189336139	1435	dbSNP
rs1010261086	1439	dbSNP
rs951745050	1440	dbSNP
rs1169390774	1441	dbSNP
rs1426338260	1445	dbSNP
rs1421452064	1446	dbSNP
rs1370737878	1457	dbSNP
rs1453536608	1462	dbSNP
rs1251072445	1465	dbSNP
rs1195364019	1467	dbSNP
rs1469926758	1467	dbSNP
rs546712964	1468	dbSNP
rs1005792641	1469	dbSNP
rs1306001998	1470	dbSNP
rs550708008	1471	dbSNP
rs1370641293	1472	dbSNP
rs1371145442	1473	dbSNP
rs1459982075	1473	dbSNP
rs570392772	1473	dbSNP
rs991624541	1473	dbSNP
rs1355950282	1474	dbSNP
rs1170630045	1475	dbSNP
rs971504385	1481	dbSNP
rs1307108378	1482	dbSNP
rs971148563	1486	dbSNP
rs1002707188	1488	dbSNP
rs1034619653	1489	dbSNP
rs1176717806	1493	dbSNP
rs1222263839	1493	dbSNP
rs1234828414	1494	dbSNP
rs181952844	1496	dbSNP
rs977516700	1498	dbSNP
rs1265537726	1499	dbSNP
rs1324789160	1500	dbSNP
rs1313319928	1505	dbSNP
rs1198423864	1507	dbSNP
rs958633610	1511	dbSNP
rs974366280	1529	dbSNP
rs1177976108	1533	dbSNP
rs935950925	1535	dbSNP
rs1266815035	1539	dbSNP
rs919860348	1542	dbSNP
rs1413787779	1546	dbSNP
rs1054376908	1547	dbSNP
rs1314512130	1550	dbSNP
rs910430557	1555	dbSNP
rs1363158179	1557	dbSNP
rs1479496418	1580	dbSNP
rs951010804	1581	dbSNP
rs371745292	1582	dbSNP
rs982423570	1583	dbSNP
rs901288672	1586	dbSNP
rs767119677	1587	dbSNP
rs998267873	1590	dbSNP
rs1470197748	1593	dbSNP
rs1483745734	1594	dbSNP
rs912306310	1596	dbSNP
rs531709410	1601	dbSNP
rs533003454	1601	dbSNP
rs780787950	1601	dbSNP
rs943827155	1603	dbSNP
rs1288399285	1604	dbSNP
rs1040530903	1606	dbSNP
rs1463244116	1608	dbSNP
rs922123364	1609	dbSNP
rs1415183187	1612	dbSNP
rs1298360704	1618	dbSNP
rs1383954297	1621	dbSNP
rs1287112014	1623	dbSNP
rs1017203924	1625	dbSNP
rs1389467439	1628	dbSNP
rs530113868	1629	dbSNP
rs1160031712	1635	dbSNP
rs145069571	1638	dbSNP
rs1415964733	1646	dbSNP
rs1013112922	1648	dbSNP
rs1261470740	1649	dbSNP
rs1284580214	1649	dbSNP
rs1203940353	1652	dbSNP
rs1487147847	1658	dbSNP
rs1346702241	1660	dbSNP
rs550214050	1662	dbSNP
rs377567951	1663	dbSNP
rs1331950428	1666	dbSNP
rs1293941396	1668	dbSNP
rs1245059041	1669	dbSNP
rs893396071	1672	dbSNP
rs1309601721	1674	dbSNP
rs1293149709	1676	dbSNP
rs971584045	1677	dbSNP
rs1010233200	1683	dbSNP
rs150511253	1684	dbSNP
rs1461000753	1688	dbSNP
rs1265073934	1689	dbSNP
rs1458579983	1691	dbSNP
rs1372921088	1692	dbSNP
rs1191521633	1693	dbSNP
rs907267980	1704	dbSNP
rs924311391	1708	dbSNP
rs1193540665	1717	dbSNP
rs1274473032	1718	dbSNP
rs1489905321	1718	dbSNP
rs1210113114	1719	dbSNP
rs139934612	1720	dbSNP
rs957063993	1729	dbSNP
rs1224817044	1733	dbSNP
rs1269643362	1734	dbSNP
rs1249220087	1747	dbSNP
rs1480737954	1755	dbSNP
rs1003398092	1759	dbSNP
rs202078152	1759	dbSNP
rs749098969	1759	dbSNP
rs1185840337	1765	dbSNP
rs1302657101	1774	dbSNP
rs1438622143	1785	dbSNP
rs910487628	1785	dbSNP
rs1325588547	1786	dbSNP
rs1387381970	1787	dbSNP
rs1396040899	1790	dbSNP
rs1034450432	1792	dbSNP
rs1166309888	1794	dbSNP
rs1463901095	1797	dbSNP
rs780271903	1802	dbSNP
rs1170782273	1804	dbSNP
rs1453094525	1805	dbSNP
rs1364588837	1808	dbSNP
rs1198993778	1810	dbSNP
rs1422293175	1811	dbSNP
rs1436656521	1817	dbSNP
rs943270878	1822	dbSNP
rs1040211928	1824	dbSNP
rs1342697323	1824	dbSNP
rs1279307130	1827	dbSNP
rs923120259	1833	dbSNP
rs1365634611	1835	dbSNP
rs1349994039	1840	dbSNP
rs1275298156	1842	dbSNP
rs1234068618	1843	dbSNP
rs768585305	1860	dbSNP
rs1335231094	1861	dbSNP
rs1327179040	1862	dbSNP
rs1287625276	1863	dbSNP
rs1371612400	1869	dbSNP
rs1364593936	1872	dbSNP
rs934107993	1878	dbSNP
rs1427872892	1884	dbSNP
rs958758238	1885	dbSNP
rs1312367358	1886	dbSNP
rs995353191	1889	dbSNP
rs1026822970	1890	dbSNP
rs1248391875	1892	dbSNP
rs1256310430	1896	dbSNP
rs1208465956	1897	dbSNP
rs1486494897	1898	dbSNP
rs1279313464	1901	dbSNP
rs1292663428	1903	dbSNP
rs1487987841	1904	dbSNP
rs1215066940	1908	dbSNP
rs551685163	1913	dbSNP
rs1230249962	1915	dbSNP
rs951336041	1915	dbSNP
rs1351370443	1917	dbSNP
rs747077877	1919	dbSNP
rs1486774673	1920	dbSNP
rs1292830636	1922	dbSNP

- Gastroenterology, 2013

BACKGROUND & AIMS: Formin-like (FMNL)2 is up-regulated in colorectal tumors and has been associated with tumor progression, but little is known about regulatory mechanisms. We investigated whether microRNAs regulate levels of FMNL2 in colorectal cancer (CRC) cells. METHODS: We used real-time polymerase chain reaction and immunoblot analyses to measure levels of miR-137, high-mobility group AT-hook (HMGA)1, and FMNL2 in CRC cells and tissue samples from patients (n = 50). We used luciferase reporter assays to determine the association between miR-137 and the FMNL2 3' untranslated region, and HMGA1 and the miR-137 promoter. Chromatin immunoprecipitation assays were used to assess direct binding of HMGA1 to the miR-137 promoter. RESULTS: miR-137 and miR-142-3p were predicted to bind FMNL2 based on bioinformatic data. Only the level of miR-137 had a significant inverse correlation with the level of FMNL2 protein in CRC cell lines and tissues. FMNL2 messenger RNA was targeted by miR-137; expression of miR-137 inhibited proliferation and invasion by CRC cells in vitro, and metastasis to liver and intestine by CRC xenografts in nude mice. HMGA1 bound to the promoter of miR-137 and activated its transcription, which reduced levels of FMNL2 in CRC cells. Ectopic expression of miR-137 in CRC cells inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, which reduced levels of matrix metalloproteinase 2, matrix metalloproteinase 9, and vascular endothelial growth factor; it also reduced invasiveness of CRC cells, inhibiting signaling via phosphatidylinositol-4,5-bisphosphate 3-kinase, Akt, and MAPK. CONCLUSIONS: Levels of miR-137 and HMGA1 are reduced, and levels of FMNL2 are increased, in CRC samples compared with adjacent normal mucosa. In CRC cells, miR-137 targets FMNL2 messenger RNA and is regulated by the transcription factor HMGA1. Expression of miR-137 reduces CRC cell invasion in vitro and metastasis of tumor xenografts in mice. FMNL2 appears to activate phosphatidylinositol-4,5-bisphosphate 3-kinase, protein kinase B (Akt), and MAPK signaling pathways.