lncRNA-在腫瘤中的作用

lncRNA在腫瘤中的作用長(zhǎng)鏈非編碼RNA(longnon-codingRNA,lncRNA)是一類轉(zhuǎn)錄本長(zhǎng)度超過(guò)200nt、不編碼蛋白的RNA，這類RNA起初被認(rèn)為是基因組轉(zhuǎn)錄的“噪音”，隨著2007年Hotair功能的被發(fā)掘，lncRNA的功能漸漸明晰。據(jù)計(jì)算，約有93%的轉(zhuǎn)錄本為lncRNA\o"Ponting,2009#19"ADDINEN.CITE<EndNote><Cite><Author>Ponting</Author><Year>2009</Year><RecNum>19</RecNum><DisplayText><styleface="superscript">1</style></DisplayText><record><rec-number>19</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">19</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ponting,ChrisP</author><author>Oliver,PeterL</author><author>Reik,Wolf</author></authors></contributors><titles><title>EvolutionandfunctionsoflongnoncodingRNAs</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>629-641</pages><volume>136</volume><number>4</number><dates><year>2009</year></dates><isbn>0092-8674</isbn><urls></urls></record></Cite></EndNote>1，lncRNA通常位于細(xì)胞核和細(xì)胞質(zhì)。但是lncRNA的基因轉(zhuǎn)錄水平一般低于蛋白質(zhì)編碼基因，序列保守性差，承受的進(jìn)化壓力小，但promoter序列通常比較保守。lncRNA與小分子RNA相比，序列更長(zhǎng)、空間結(jié)構(gòu)也較為復(fù)雜，參與表達(dá)調(diào)控的機(jī)制也更具有多樣性和復(fù)雜性。盡管目前只有一小部分lncRNA的功能有相關(guān)報(bào)道，但可以明確的是lncRNA參與發(fā)育、分化、代謝等多方面的調(diào)控。lncRNA在癌癥中顯示出多種生物學(xué)功能：包括表觀遺傳調(diào)控、DNA損傷和細(xì)胞周期調(diào)控、對(duì)microRNA的調(diào)控、參與信號(hào)轉(zhuǎn)導(dǎo)通路和介導(dǎo)激素導(dǎo)致的癌癥\o"Sahu,2015#20"ADDINEN.CITE<EndNote><Cite><Author>Sahu</Author><Year>2015</Year><RecNum>20</RecNum><DisplayText><styleface="superscript">2</style></DisplayText><record><rec-number>20</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">20</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Sahu,Anirban</author><author>Singhal,Udit</author><author>Chinnaiyan,ArulM</author></authors></contributors><titles><title>LongnoncodingRNAsincancer:fromfunctiontotranslation</title><secondary-title>TrendsinCancer</secondary-title></titles><periodical><full-title>TrendsinCancer</full-title></periodical><pages>93-109</pages><volume>1</volume><number>2</number><dates><year>2015</year></dates><isbn>2405-8033</isbn><urls></urls></record></Cite></EndNote>2。在癌癥中，lncRNA可以作為癌基因和抑癌基因的轉(zhuǎn)錄調(diào)控分子\o"Prensner,2011#21"ADDINEN.CITE<EndNote><Cite><Author>Prensner</Author><Year>2011</Year><RecNum>21</RecNum><DisplayText><styleface="superscript">3</style></DisplayText><record><rec-number>21</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">21</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Prensner,JohnR</author><author>Chinnaiyan,ArulM</author></authors></contributors><titles><title>TheemergenceoflncRNAsincancerbiology</title><secondary-title>Cancerdiscovery</secondary-title></titles><periodical><full-title>Cancerdiscovery</full-title></periodical><pages>391-407</pages><volume>1</volume><number>5</number><dates><year>2011</year></dates><isbn>2159-8274</isbn><urls></urls></record></Cite></EndNote>3。比如過(guò)表達(dá)的HOTAIRlncRNA與惡性乳腺癌\o"Gupta,2010#22"ADDINEN.CITE<EndNote><Cite><Author>Gupta</Author><Year>2010</Year><RecNum>22</RecNum><DisplayText><styleface="superscript">4</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">22</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gupta,RajnishA</author><author>Shah,Nilay</author><author>Wang,KevinC</author><author>Kim,Jeewon</author><author>Horlings,HugoM</author><author>Wong,DavidJ</author><author>Tsai,Miao-Chih</author><author>Hung,Tiffany</author><author>Argani,Pedram</author><author>Rinn,JohnL</author></authors></contributors><titles><title>Longnon-codingRNAHOTAIRreprogramschromatinstatetopromotecancermetastasis</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>1071-1076</pages><volume>464</volume><number>7291</number><dates><year>2010</year></dates><isbn>0028-0836</isbn><urls></urls></record></Cite></EndNote>4、結(jié)腸癌\o"Kogo,2011#23"ADDINEN.CITE<EndNote><Cite><Author>Kogo</Author><Year>2011</Year><RecNum>23</RecNum><DisplayText><styleface="superscript">5</style></DisplayText><record><rec-number>23</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">23</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kogo,Ryunosuke</author><author>Shimamura,Teppei</author><author>Mimori,Koshi</author><author>Kawahara,Kohichi</author><author>Imoto,Seiya</author><author>Sudo,Tomoya</author><author>Tanaka,Fumiaki</author><author>Shibata,Kohei</author><author>Suzuki,Akira</author><author>Komune,Shizuo</author></authors></contributors><titles><title>LongnoncodingRNAHOTAIRregulatespolycomb-dependentchromatinmodificationandisassociatedwithpoorprognosisincolorectalcancers</title><secondary-title>Cancerresearch</secondary-title></titles><periodical><full-title>Cancerresearch</full-title></periodical><pages>6320-6326</pages><volume>71</volume><number>20</number><dates><year>2011</year></dates><isbn>0008-5472</isbn><urls></urls></record></Cite></EndNote>5、肝癌\o"Yang,2011#24"ADDINEN.CITE<EndNote><Cite><Author>Yang</Author><Year>2011</Year><RecNum>24</RecNum><DisplayText><styleface="superscript">6</style></DisplayText><record><rec-number>24</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">24</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Yang,Zhe</author><author>Zhou,Lin</author><author>Wu,Li-Ming</author><author>Lai,Ming-Chun</author><author>Xie,Hai-Yang</author><author>Zhang,Feng</author><author>Zheng,Shu-Sen</author></authors></contributors><titles><title>Overexpressionoflongnon-codingRNAHOTAIRpredictstumorrecurrenceinhepatocellularcarcinomapatientsfollowinglivertransplantation</title><secondary-title>Annalsofsurgicaloncology</secondary-title></titles><periodical><full-title>Annalsofsurgicaloncology</full-title></periodical><pages>1243-1250</pages><volume>18</volume><number>5</number><dates><year>2011</year></dates><isbn>1068-9265</isbn><urls></urls></record></Cite></EndNote>6和胃腸道間質(zhì)瘤\o"Niinuma,2012#25"ADDINEN.CITE<EndNote><Cite><Author>Niinuma</Author><Year>2012</Year><RecNum>25</RecNum><DisplayText><styleface="superscript">7</style></DisplayText><record><rec-number>25</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">25</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Niinuma,Takeshi</author><author>Suzuki,Hiromu</author><author>Nojima,Masanori</author><author>Nosho,Katsuhiko</author><author>Yamamoto,Hiroyuki</author><author>Takamaru,Hiroyuki</author><author>Yamamoto,Eiichiro</author><author>Maruyama,Reo</author><author>Nobuoka,Takayuki</author><author>Miyazaki,Yasuaki</author></authors></contributors><titles><title>UpregulationofmiR-196aandHOTAIRdrivemalignantcharacteringastrointestinalstromaltumors</title><secondary-title>Cancerresearch</secondary-title></titles><periodical><full-title>Cancerresearch</full-title></periodical><pages>1126-1136</pages><volume>72</volume><number>5</number><dates><year>2012</year></dates><isbn>0008-5472</isbn><urls></urls></record></Cite></EndNote>7有關(guān)。而lncRNATARID可以預(yù)防癌癥形成，通過(guò)甲基化抑癌基因的表達(dá)\o"Arab,2014#26"ADDINEN.CITE<EndNote><Cite><Author>Arab</Author><Year>2014</Year><RecNum>26</RecNum><DisplayText><styleface="superscript">8</style></DisplayText><record><rec-number>26</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">26</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Arab,Khelifa</author><author>Park,YoonJung</author><author>Lindroth,AndersM</author><author>Sch?fer,Andrea</author><author>Oakes,Christopher</author><author>Weichenhan,Dieter</author><author>Lukanova,Annekatrin</author><author>Lundin,Eva</author><author>Risch,Angela</author><author>Meister,Michael</author></authors></contributors><titles><title>LongnoncodingRNATARIDdirectsdemethylationandactivationofthetumorsuppressorTCF21viaGADD45A</title><secondary-title>Molecularcell</secondary-title></titles><periodical><full-title>Molecularcell</full-title></periodical><pages>604-614</pages><volume>55</volume><number>4</number><dates><year>2014</year></dates><isbn>1097-2765</isbn><urls></urls></record></Cite></EndNote>8。表觀遺傳調(diào)控表觀遺傳是指遺傳表型和基因表達(dá)發(fā)生了可遺傳的改變，而不涉及DNA序列的變化，主要包括DNA甲基化、組蛋白修飾和染色質(zhì)重塑等修飾形式。近年來(lái)研究表明，lncRNAs通過(guò)表觀遺傳調(diào)控介導(dǎo)癌癥發(fā)生中起到至關(guān)重要的作用。lncRNAs能夠通過(guò)表觀遺傳調(diào)控、轉(zhuǎn)錄調(diào)控以及轉(zhuǎn)錄后調(diào)控等多個(gè)層面調(diào)節(jié)基因的表達(dá)，從而參與癌癥中細(xì)胞增殖、分化和凋亡等多種生物學(xué)過(guò)程\o"Sharma,2010#27"ADDINEN.CITE<EndNote><Cite><Author>Sharma</Author><Year>2010</Year><RecNum>27</RecNum><DisplayText><styleface="superscript">9</style></DisplayText><record><rec-number>27</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">27</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Sharma,Shikhar</author><author>Kelly,TheresaK</author><author>Jones,PeterA</author></authors></contributors><titles><title>Epigeneticsincancer</title><secondary-title>Carcinogenesis</secondary-title></titles><periodical><full-title>Carcinogenesis</full-title></periodical><pages>27-36</pages><volume>31</volume><number>1</number><dates><year>2010</year></dates><isbn>0143-3334</isbn><urls></urls></record></Cite></EndNote>9。在癌癥發(fā)展過(guò)程中，lncRNAs參與了多種表觀遺傳復(fù)合物的調(diào)節(jié)過(guò)程，從而抑制或激活基因的表達(dá)。例如，lncRNAs可以與多梳蛋白復(fù)合體結(jié)合來(lái)調(diào)控癌癥發(fā)生\o"Gupta,2010#22"ADDINEN.CITE<EndNote><Cite><Author>Gupta</Author><Year>2010</Year><RecNum>22</RecNum><DisplayText><styleface="superscript">4</style></DisplayText><record><rec-number>22</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">22</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gupta,RajnishA</author><author>Shah,Nilay</author><author>Wang,KevinC</author><author>Kim,Jeewon</author><author>Horlings,HugoM</author><author>Wong,DavidJ</author><author>Tsai,Miao-Chih</author><author>Hung,Tiffany</author><author>Argani,Pedram</author><author>Rinn,JohnL</author></authors></contributors><titles><title>Longnon-codingRNAHOTAIRreprogramschromatinstatetopromotecancermetastasis</title><secondary-title>Nature</secondary-title></titles><periodical><full-title>Nature</full-title></periodical><pages>1071-1076</pages><volume>464</volume><number>7291</number><dates><year>2010</year></dates><isbn>0028-0836</isbn><urls></urls></record></Cite></EndNote>4。PRC1和2是已知的致癌基因，能夠?qū)е略S多惡性腫瘤的發(fā)生。FAL1lncRNA與PRC1的亞基BMI1結(jié)合。在卵巢癌,FAL1被證明可以加快癌癥的進(jìn)展和縮短病人的生存時(shí)間。FAL1與BMI1結(jié)合可阻止BMI1降解以穩(wěn)定PRC1復(fù)合物，這可使PRC1占據(jù)和抑制p21等目標(biāo)基因的啟動(dòng)子,導(dǎo)致細(xì)胞周期失調(diào)和增加腫瘤發(fā)生的機(jī)會(huì)\o"Puvvula,2014#28"ADDINEN.CITE<EndNote><Cite><Author>Puvvula</Author><Year>2014</Year><RecNum>28</RecNum><DisplayText><styleface="superscript">10</style></DisplayText><record><rec-number>28</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">28</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Puvvula,PavanKumar</author><author>Desetty,RohiniDevi</author><author>Pineau,Pascal</author><author>Marchio,Agnés</author><author>Moon,Anne</author><author>Dejean,Anne</author><author>Bischof,Oliver</author></authors></contributors><titles><title>LongnoncodingRNAPANDAandscaffold-attachment-factorSAFAcontrolsenescenceentryandexit</title><secondary-title>Naturecommunications</secondary-title></titles><periodical><full-title>Naturecommunications</full-title></periodical><volume>5</volume><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>10。除了PRC復(fù)合物,lncRNAs還與SWI/SNF染色質(zhì)重塑復(fù)合物有關(guān)，SWI/SNF是一類重要的依賴ATP的染色質(zhì)重塑復(fù)合物,能夠改變核小體的高級(jí)折疊結(jié)構(gòu)，干擾組蛋白與DNA結(jié)合，暴露啟動(dòng)子序列的結(jié)合位點(diǎn)，使轉(zhuǎn)錄因子能與特異性啟動(dòng)子序列結(jié)合，從而激活基因轉(zhuǎn)錄\o"Prensner,2013#29"ADDINEN.CITEADDINEN.CITE.DATA11-14。在癌癥中,SWI/SNF染色質(zhì)重塑復(fù)合物被廣泛認(rèn)為是一種腫瘤抑制分子，因?yàn)橛泻ν蛔兂霈F(xiàn)在大約20%的癌癥中\(zhòng)o"Reisman,2009#33"ADDINEN.CITE<EndNote><Cite><Author>Reisman</Author><Year>2009</Year><RecNum>33</RecNum><DisplayText><styleface="superscript">15</style></DisplayText><record><rec-number>33</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">33</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Reisman,D</author><author>Glaros,S</author><author>Thompson,EA</author></authors></contributors><titles><title>TheSWI/SNFcomplexandcancer</title><secondary-title>Oncogene</secondary-title></titles><periodical><full-title>Oncogene</full-title></periodical><pages>1653-1668</pages><volume>28</volume><number>14</number><dates><year>2009</year></dates><isbn>0950-9232</isbn><urls></urls></record></Cite></EndNote>15。LncTCF7在肝癌細(xì)胞(HCC)高表達(dá)，在肝癌干細(xì)胞的自我更新能力的維護(hù)中起重要作用\o"Wang,2015#34"ADDINEN.CITE<EndNote><Cite><Author>Wang</Author><Year>2015</Year><RecNum>34</RecNum><DisplayText><styleface="superscript">12</style></DisplayText><record><rec-number>34</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">34</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wang,Yanying</author><author>He,Lei</author><author>Du,Ying</author><author>Zhu,Pingping</author><author>Huang,Guanling</author><author>Luo,Jianjun</author><author>Yan,Xinlong</author><author>Ye,Buqing</author><author>Li,Chong</author><author>Xia,Pengyan</author></authors></contributors><titles><title>TheLongNoncodingRNAlncTCF7PromotesSelf-RenewalofHumanLiverCancerStemCellsthroughActivationofWntSignaling</title><secondary-title>Cellstemcell</secondary-title></titles><periodical><full-title>Cellstemcell</full-title></periodical><pages>413-425</pages><volume>16</volume><number>4</number><dates><year>2015</year></dates><isbn>1934-5909</isbn><urls></urls></record></Cite></EndNote>12。LncTCF7可以激活Wnt信號(hào)通路，通過(guò)結(jié)合和募集SWI/SNF復(fù)合物來(lái)與TCF7基因的啟動(dòng)子結(jié)合激活基因的表達(dá)，這導(dǎo)致了肝癌腫瘤的發(fā)生。除此以外，lncRNAs還可以參與由DNA甲基化、乙酰化等介導(dǎo)的基因轉(zhuǎn)錄過(guò)程來(lái)調(diào)控腫瘤發(fā)生過(guò)程。DNA損傷和細(xì)胞周期調(diào)控lncRNAs廣泛參與DNA損傷修復(fù)、細(xì)胞周期調(diào)控等生理或病理過(guò)程調(diào)控腫瘤的發(fā)生發(fā)展。對(duì)DNA損傷進(jìn)行修復(fù)和細(xì)胞周期檢查點(diǎn)的適當(dāng)調(diào)節(jié)對(duì)于維持細(xì)胞的完整性識(shí)有明顯的增長(zhǎng)，但這只是冰山一角，lncRNAs在癌癥中行使的復(fù)雜生物學(xué)功能，其詳細(xì)的調(diào)控機(jī)制仍有待深入研究。參考文獻(xiàn)ADDINEN.REFLIST1. PontingCP,OliverPL,ReikW.EvolutionandfunctionsoflongnoncodingRNAs.Cell.2009;136(4):629-41.2. SahuA,SinghalU,ChinnaiyanAM.LongnoncodingRNAsincancer:fromfunctiontotranslation.TrendsinCancer.2015;1(2):93-109.3. PrensnerJR,ChinnaiyanAM.TheemergenceoflncRNAsincancerbiology.Cancerdiscovery.2011;1(5):391-407.4. GuptaRA,ShahN,WangKC,KimJ,HorlingsHM,WongDJ,etal.Longnon-codingRNAHOTAIRreprogramschromatinstatetopromotecancermetastasis.Nature.2010;464(7291):1071-6.5. KogoR,ShimamuraT,MimoriK,KawaharaK,ImotoS,SudoT,etal.LongnoncodingRNAHOTAIRregulatespolycomb-dependentchromatinmodificationandisassociatedwithpoorprognosisincolorectalcancers.Cancerresearch.2011;71(20):6320-6.6. YangZ,ZhouL,WuL-M,LaiM-C,XieH-Y,ZhangF,etal.Overexpressionoflongnon-codingRNAHOTAIRpredictstumorrecurrenceinhepatocellularcarcinomapatientsfollowinglivertransplantation.Annalsofsurgicaloncology.2011;18(5):1243-50.7. NiinumaT,SuzukiH,NojimaM,NoshoK,YamamotoH,TakamaruH,etal.UpregulationofmiR-196aandHOTAIRdrivemalignantcharacteringastrointestinalstromaltumors.Cancerresearch.2012;72(5):1126-36.8. ArabK,ParkYJ,LindrothAM,Sch?ferA,OakesC,WeichenhanD,etal.LongnoncodingRNATARIDdirectsdemethylationandactivationofthetumorsuppressorTCF21viaGADD45A.Molecularcell.2014;55(4):604-14.9. SharmaS,KellyTK,JonesPA.Epigeneticsincancer.Carcinogenesis.2010;31(1):27-36.10. PuvvulaPK,DesettyRD,PineauP,MarchioA,MoonA,DejeanA,etal.LongnoncodingRNAPANDAandscaffold-attachment-factorSAFAcontrolsenescenceentryandexit.Naturecommunications.2014;5.11. PrensnerJR,IyerMK,SahuA,AsanganiIA,CaoQ,PatelL,etal.ThelongnoncodingRNASChLAP1promotesaggressiveprostatecancerandantagonizestheSWI/SNFcomplex.Naturegenetics.2013;45(11):1392-8.12. WangY,HeL,DuY,ZhuP,HuangG,LuoJ,etal.TheLongNoncodingRNAlncTCF7PromotesSelf-RenewalofHumanLiverCancerStemCellsthroughActivationofWntSignaling.Cellstemcell.2015;16(4):413-25.13. ZhuY,RowleyMJ,B?hmdorferG,WierzbickiAT.ASWI/SNFchromatin-remodelingcomplexactsinnoncodingRNA-mediatedtranscriptionalsilencing.Molecularcell.2013;49(2):298-309.14. HanP,LiW,LinC-H,YangJ,ShangC,NuernbergST,etal.AlongnoncodingRNAprotectstheheartfrompathologicalhypertrophy.Nature.2014.15. ReismanD,GlarosS,ThompsonE.TheSWI/SNFcomplexandcancer.Oncogene.2009;28(14):1653-68.16. MullerPA,VousdenKH.p53mutationsincancer.Naturecellbiology.2013;15(1):2-8.17. VazquezA,BondEE,LevineAJ,BondGL.Thegeneticsofthep53pathway,apoptosisandcancertherapy.NaturereviewsDrugdiscovery.2008;7(12):979-87.18. DimitrovaN,ZamudioJR,JongRM,SoukupD,ResnickR,SarmaK,etal.LincRNA-p21activatesp21incistopromotePolycombtargetgeneexpressionandtoenforcetheG1/Scheckpoint.Molecularcell.2014;54(5):777-90.19. LiuX,LiD,ZhangW,GuoM,ZhanQ.Longnon‐codingRNAgadd7interactswithTDP‐43andregulatesCdk6mRNAdecay.TheEMBOjournal.2012;31(23):4415-27.20. IorioMV,CroceCM.MicroRNAdysregulationincancer:diagnostics,monitoringandtherapeutics.Acomprehensivereview.EMBOmolecularmedicine.2012;4(3):143-59.21. SalmenaL,PolisenoL,TayY,KatsL,PandolfiPP.AceRNAhypothesis:theRosettaStoneofahiddenRNAlanguage?Cell.2011;146(3):353-8.22. DenzlerR,AgarwalV,StefanoJ,BartelDP,StoffelM.AssessingtheceRNAhypothesiswithquantitativemeasurementsofmiRNAandtargetabundance.Molecularcell.2014;54(5):766-76.23. CuiH,OnyangoP,BrandenburgS,WuY,HsiehC-L,FeinbergAP.LossofimprintingincolorectalcancerlinkedtohypomethylationofH19andIGF2.Cancerresearch.2002;62(22):6442-6.24. ZhuangM,GaoW,XuJ,WangP,ShuY.Thelongnon-codingRNAH19-derivedmiR-675modulateshumangastriccancercellproliferationbytargetingtumorsuppressorRUNX1.Biochemicalandbiophysicalresearchcommunications.2014;448(3):315-22.25. Tsang