國家自然基金申請書寫作：lncRNA 在腫瘤中的作用

lncRNA在腫瘤中的作用長鏈非編碼RNA(longnon-codingRNA,lncRNA)是一類轉(zhuǎn)錄本長度超過200nt、不編碼蛋白的RNA，這類RNA起初被認為是基因組轉(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通常位于細胞核和細胞質(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、空間結(jié)構(gòu)也較為復雜，參與表達調(diào)控的機制也更具有多樣性和復雜性。盡管目前只有一小部分lncRNA的功能有相關(guān)報道，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功能：包括表觀遺傳調(diào)控、DNA損傷和細胞周期調(diào)控、對microRNA的調(diào)控、參與信號轉(zhuǎn)導通路和介導激素導致的癌癥\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。比如過表達的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可以預防癌癥形成，通過甲基化抑癌基因的表達\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。近年來研究表明，lncRNAs通過表觀遺傳調(diào)控介導癌癥發(fā)生中起到至關(guān)重要的作用。lncRNAs能夠通過表觀遺傳調(diào)控、轉(zhuǎn)錄調(diào)控以及轉(zhuǎn)錄后調(diào)控等多個層面調(diào)節(jié)基因的表達，從而參與癌癥中細胞增殖、分化和凋亡等多種生物學過程\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)展過程中，lncRNAs參與了多種表觀遺傳復合物的調(diào)節(jié)過程，從而抑制或激活基因的表達。例如，lncRNAs可以與多梳蛋白復合體結(jié)合來調(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展和縮短病人的生存時間。FAL1與BMI1結(jié)合可阻止BMI1降解以穩(wěn)定PRC1復合物，這可使PRC1占據(jù)和抑制p21等目標基因的啟動子,導致細胞周期失調(diào)和增加腫瘤發(fā)生的機會\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復合物,lncRNAs還與SWI/SNF染色質(zhì)重塑復合物有關(guān)，SWI/SNF是一類重要的依賴ATP的染色質(zhì)重塑復合物,能夠改變核小體的高級折疊結(jié)構(gòu)，干擾組蛋白與DNA結(jié)合，暴露啟動子序列的結(jié)合位點，使轉(zhuǎn)錄因子能與特異性啟動子序列結(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)重塑復合物被廣泛認為是一種腫瘤抑制分子，因為有害突變出現(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在肝癌細胞(HCC)高表達，在肝癌干細胞的自我更新能力的維護中起重要作用\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信號通路，通過結(jié)合和募集SWI/SNF復合物來與TCF7基因的啟動子結(jié)合激活基因的表達，這導致了肝癌腫瘤的發(fā)生。除此以外，lncRNAs還可以參與由DNA甲基化、乙酰化等介導的基因轉(zhuǎn)錄過程來調(diào)控腫瘤發(fā)生過程。DNA損傷和細胞周期調(diào)控lncRNAs廣泛參與DNA損傷修復、細胞周期調(diào)控等生理或病理過程調(diào)控腫瘤的發(fā)生發(fā)展。對DNA損傷進行修復和細胞周期檢查點的適當調(diào)節(jié)對于維持細胞的完整性很重要\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。p53基因是研究最廣泛的抑癌基因之一,也是細胞內(nèi)的一個強大的轉(zhuǎn)錄因子,在正常狀態(tài)下呈低水平表達。在各種應激包括DNA損傷時,p53可以被不同的信號通路激活,通過增強其下游多種基因的轉(zhuǎn)錄而引起細胞周期阻滯、凋亡或衰老,保持細胞基因組的完整性并清除損傷細胞ADDINEN.CITE<EndNote><Cite><Author>Muller</Author><Year>2013</Year><RecNum>35</RecNum><DisplayText><styleface="superscript">16,17</style></DisplayText><record><rec-number>35</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">35</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Muller,PatriciaAJ</author><author>Vousden,KarenH</author></authors></contributors><titles><title>p53mutationsincancer</title><secondary-title>Naturecellbiology</secondary-title></titles><periodical><full-title>Naturecellbiology</full-title></periodical><pages>2-8</pages><volume>15</volume><number>1</number><dates><year>2013</year></dates><isbn>1465-7392</isbn><urls></urls></record></Cite><Cite><Author>Vazquez</Author><Year>2008</Year><RecNum>36</RecNum><record><rec-number>36</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">36</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vazquez,Alexei</author><author>Bond,ElisabethE</author><author>Levine,ArnoldJ</author><author>Bond,GarethL</author></authors></contributors><titles><title>Thegeneticsofthep53pathway,apoptosisandcancertherapy</title><secondary-title>NaturereviewsDrugdiscovery</secondary-title></titles><periodical><full-title>NaturereviewsDrugdiscovery</full-title></periodical><pages>979-987</pages><volume>7</volume><number>12</number><dates><year>2008</year></dates><isbn>1474-1776</isbn><urls></urls></record></Cite></EndNote>\o"Muller,2013#35"16,\o"Vazquez,2008#36"17。在癌癥中，lncRNAs作為調(diào)控分子調(diào)控P53基因和細胞周期\o"Vazquez,2008#36"ADDINEN.CITE<EndNote><Cite><Author>Vazquez</Author><Year>2008</Year><RecNum>36</RecNum><DisplayText><styleface="superscript">17</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">36</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Vazquez,Alexei</author><author>Bond,ElisabethE</author><author>Levine,ArnoldJ</author><author>Bond,GarethL</author></authors></contributors><titles><title>Thegeneticsofthep53pathway,apoptosisandcancertherapy</title><secondary-title>NaturereviewsDrugdiscovery</secondary-title></titles><periodical><full-title>NaturereviewsDrugdiscovery</full-title></periodical><pages>979-987</pages><volume>7</volume><number>12</number><dates><year>2008</year></dates><isbn>1474-1776</isbn><urls></urls></record></Cite></EndNote>17。例如，lincRNA-p21召集核糖核蛋白hnRNP-k來促進P21的轉(zhuǎn)錄，P21是一種調(diào)控p53信號通路的關(guān)鍵分子。lincRNA-p21的缺失使得G1/S檢查點失控導致細胞的增殖增加\o"Dimitrova,2014#37"ADDINEN.CITE<EndNote><Cite><Author>Dimitrova</Author><Year>2014</Year><RecNum>37</RecNum><DisplayText><styleface="superscript">18</style></DisplayText><record><rec-number>37</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">37</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Dimitrova,Nadya</author><author>Zamudio,JesseR</author><author>Jong,RobynM</author><author>Soukup,Dylan</author><author>Resnick,Rebecca</author><author>Sarma,Kavitha</author><author>Ward,AmandaJ</author><author>Raj,Arjun</author><author>Lee,JeannieT</author><author>Sharp,PhillipA</author></authors></contributors><titles><title>LincRNA-p21activatesp21incistopromotePolycombtargetgeneexpressionandtoenforcetheG1/Scheckpoint</title><secondary-title>Molecularcell</secondary-title></titles><periodical><full-title>Molecularcell</full-title></periodical><pages>777-790</pages><volume>54</volume><number>5</number><dates><year>2014</year></dates><isbn>1097-2765</isbn><urls></urls></record></Cite></EndNote>18。還有，lncRNAgadd7可抑制細胞周期G1/S期轉(zhuǎn)換，在DNA受到紫外線、鉑順化合物和生長抑制等損傷時會誘導lncRNAgadd7的表達\o"Liu,2012#38"ADDINEN.CITE<EndNote><Cite><Author>Liu</Author><Year>2012</Year><RecNum>38</RecNum><DisplayText><styleface="superscript">19</style></DisplayText><record><rec-number>38</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">38</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Liu,Xuefeng</author><author>Li,Dan</author><author>Zhang,Weimin</author><author>Guo,Mingzhou</author><author>Zhan,Qimin</author></authors></contributors><titles><title>Longnon‐codingRNAgadd7interactswithTDP‐43andregulatesCdk6mRNAdecay</title><secondary-title>TheEMBOjournal</secondary-title></titles><periodical><full-title>TheEMBOjournal</full-title></periodical><pages>4415-4427</pages><volume>31</volume><number>23</number><dates><year>2012</year></dates><isbn>0261-4189</isbn><urls></urls></record></Cite></EndNote>19。總的來說，這些機制表明lncRNAs在DNA損傷修復、細胞周期過程、細胞凋亡調(diào)控中是至關(guān)重要的把關(guān)分子，在這些過程中，lncRNA的失調(diào)會讓癌細胞獲得永生性。與miRNA的作用microRNA與很多疾病的發(fā)生發(fā)展有關(guān)，包括癌癥\o"Iorio,2012#39"ADDINEN.CITE<EndNote><Cite><Author>Iorio</Author><Year>2012</Year><RecNum>39</RecNum><DisplayText><styleface="superscript">20</style></DisplayText><record><rec-number>39</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">39</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Iorio,MarilenaV</author><author>Croce,CarloM</author></authors></contributors><titles><title>MicroRNAdysregulationincancer:diagnostics,monitoringandtherapeutics.Acomprehensivereview</title><secondary-title>EMBOmolecularmedicine</secondary-title></titles><periodical><full-title>EMBOmolecularmedicine</full-title></periodical><pages>143-159</pages><volume>4</volume><number>3</number><dates><year>2012</year></dates><isbn>1757-4676</isbn><urls></urls></record></Cite></EndNote>20。miRNA可與靶RNA互補配對，導致基因的表達受制和蛋白合成受阻\o"Salmena,2011#40"ADDINEN.CITE<EndNote><Cite><Author>Salmena</Author><Year>2011</Year><RecNum>40</RecNum><DisplayText><styleface="superscript">21</style></DisplayText><record><rec-number>40</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">40</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Salmena,Leonardo</author><author>Poliseno,Laura</author><author>Tay,Yvonne</author><author>Kats,Lev</author><author>Pandolfi,PierPaolo</author></authors></contributors><titles><title>AceRNAhypothesis:theRosettaStoneofahiddenRNAlanguage?</title><secondary-title>Cell</secondary-title></titles><periodical><full-title>Cell</full-title></periodical><pages>353-358</pages><volume>146</volume><number>3</number><dates><year>2011</year></dates><isbn>0092-8674</isbn><urls></urls></record></Cite></EndNote>21。LncRNAs可與microRNA直接或間接作用，導致其失去調(diào)節(jié)功能。競爭性內(nèi)源RNA(ceRNA)假說是一種全新的基因表達調(diào)控模式，長鏈非編碼RNA轉(zhuǎn)錄物通過microRNA應答元件競爭結(jié)合相同的microRNA來調(diào)控各自的表達水平，從而影響細胞的功能\o"Denzler,2014#41"ADDINEN.CITE<EndNote><Cite><Author>Denzler</Author><Year>2014</Year><RecNum>41</RecNum><DisplayText><styleface="superscript">22</style></DisplayText><record><rec-number>41</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">41</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Denzler,Rémy</author><author>Agarwal,Vikram</author><author>Stefano,Joanna</author><author>Bartel,DavidP</author><author>Stoffel,Markus</author></authors></contributors><titles><title>AssessingtheceRNAhypothesiswithquantitativemeasurementsofmiRNAandtargetabundance</title><secondary-title>Molecularcell</secondary-title></titles><periodical><full-title>Molecularcell</full-title></periodical><pages>766-776</pages><volume>54</volume><number>5</number><dates><year>2014</year></dates><isbn>1097-2765</isbn><urls></urls></record></Cite></EndNote>22。例如，H19lncRNA，是一個被研究了數(shù)十年的重要的癌癥發(fā)生遺傳因素\o"Cui,2002#42"ADDINEN.CITE<EndNote><Cite><Author>Cui</Author><Year>2002</Year><RecNum>42</RecNum><DisplayText><styleface="superscript">23</style></DisplayText><record><rec-number>42</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">42</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cui,Hengmi</author><author>Onyango,Patrick</author><author>Brandenburg,Sheri</author><author>Wu,Yiqian</author><author>Hsieh,Chih-Lin</author><author>Feinberg,AndrewP</author></authors></contributors><titles><title>LossofimprintingincolorectalcancerlinkedtohypomethylationofH19andIGF2</title><secondary-title>Cancerresearch</secondary-title></titles><periodical><full-title>Cancerresearch</full-title></periodical><pages>6442-6446</pages><volume>62</volume><number>22</number><dates><year>2002</year></dates><isbn>0008-5472</isbn><urls></urls></record></Cite></EndNote>23。H19lncRNA編碼和產(chǎn)生mir-675促進胃癌\o"Zhuang,2014#43"ADDINEN.CITE<EndNote><Cite><Author>Zhuang</Author><Year>2014</Year><RecNum>43</RecNum><DisplayText><styleface="superscript">24</style></DisplayText><record><rec-number>43</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">43</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhuang,Ming</author><author>Gao,Wen</author><author>Xu,Jing</author><author>Wang,Ping</author><author>Shu,Yongqian</author></authors></contributors><titles><title>Thelongnon-codingRNAH19-derivedmiR-675modulateshumangastriccancercellproliferationbytargetingtumorsuppressorRUNX1</title><secondary-title>Biochemicalandbiophysicalresearchcommunications</secondary-title></titles><periodical><full-title>Biochemicalandbiophysicalresearchcommunications</full-title></periodical><pages>315-322</pages><volume>448</volume><number>3</number><dates><year>2014</year></dates><isbn>0006-291X</isbn><urls></urls></record></Cite></EndNote>24、結(jié)直腸癌\o"Tsang,2010#44"ADDINEN.CITE<EndNote><Cite><Author>Tsang</Author><Year>2010</Year><RecNum>44</RecNum><DisplayText><styleface="superscript">25</style></DisplayText><record><rec-number>44</rec-number><foreign-keys><keyapp="EN"db-id="9sf2daeww0wedaevdp85dftp0zss5p2xdxs0">44</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Tsang,WingPui</author><author>Ng,EndersKO</author><author>Ng,SimonSM</author><author>Jin,Hongchuan</author><author>Yu,Jun</author><author>Sung,JosephJY</author><author>Kwok,TimTak</author></authors></contributors><titles><title>OncofetalH19-derivedmiR-675regulatestumorsuppressorRBinhumancolorectalcancer</title><secondary-title>Carcinogenesis</secondary-title></titles><periodical><full-title>Carcinogenesis</full-title></periodical><pages>350-358</pages><volume>31</volume><number>3</number><dates><year>2010</year></dates><isbn>0143-3334</isbn><urls></urls></record></Cite></EndNote>25、神經(jīng)膠質(zhì)瘤\o"S