CN106148348A - 一组胃癌rna分子标志物及其应用 - Google Patents
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Abstract
本发明属于生物医药领域，具体涉及多种RNA及其不同组合的肿瘤标志物及其在制备诊断胃癌试剂中的应用。本发明为胃癌的诊断提供了一组新RNA分子标志物。该组RNA在胃癌组织中的含量比癌旁组织高，而且在胃癌患者血浆中的含量比健康人血浆中的含量高。本发明还提供了该组RNA中的一个或不同组合用作胃癌标志物的方法与用途。使用该组RNA分子标志物及含有该组RNA标志物不同组合的诊断方法诊断胃癌，操作简单、取材方便，具有高特异性、高灵敏性和易于大量筛查的特点。该组RNA分子标志物适合应用于胃癌高危人群的筛查和胃癌的辅助诊断。
Description
技术领域
本发明属于生物医药领域，具体涉及多种RNA及其不同组合的肿瘤标志物及其在制备诊断胃癌试剂中的应用。
背景技术
胃癌是最常见的恶性肿瘤之一，因缺乏有效的早期诊断手段,早期筛查发现肿瘤较困难.目前胃癌的主要诊断方式有胃镜、CT或PET/CT等,这些检查手段成本高且有创,无法有效地筛查出早期的胃癌患者。而经典的肿瘤标志物如CEA、CA724、CA19-9等,由于缺乏较强的敏感性及特异性而局限。 越来越多的研究发现多种非编码RNA参与调控肿瘤细胞的增殖、凋亡等生物学过程，直接或间接发挥着癌基因或抑癌基因的功能，在肿瘤的发生、发展中起至关重要作用。长链非编码RNA（lncRNA）是一类长度大于200个核苷酸左右的非编码RNA分子,其主要通过直接或间接影响相关基因或蛋白质的表达水平或结构等来发挥其肿瘤基因的功能，lncRNA在肿瘤中的表达异常,与肿瘤形成、进展有密切联系,可以作为肿瘤诊断及治疗的靶分子。由于肿瘤标本来源的限制，使得临床上应用组织RNA存在一定局限性，而外周血标本获得方便，如果能在血液中检出癌症特异性的microRNA、lncRNA及mRNA并将其作为癌症的生物学标志，对于癌症的早期诊断具有重要意义。进一步的研究发现RNA分子在外周血中的表达同样具有肿瘤相关性和组织特异性，外周血RNA可能成为理想的肿瘤标志物，并且血浆可以作为一种有效、无创的筛查手段，因此血浆等体液中的RNA分子适合作为诊断早期胃癌的潜在肿瘤标志物。本发明提供一组RNA分子,用于胃癌患者的诊断及胃癌的早期诊断,具有高的敏感性及特异性。
发明内容
本发明的目的在于对现有胃癌检测标志物的补充，提供胃癌患者血浆中循环RNA标志物及检测分析方法，为临床上胃癌患者的早期发现及诊断治疗提供支持。
本发明公开了用于通过分析RNA分子标志物来表征表型的方法和组合物。本发明提供了一组胃癌RNA标志物，其特征在于，所述RNA分子选自:1)序列表中所示的RNA分子及其组合，AK001058序列如SEQ ID NO.1所示；INHBA-AS1(NR_027118)序列如SEQ ID NO.2所示，MIR4435-2HG(NR_015395)序列如SEQ ID NO.3所示，CEBPA-AS1(NR_026887)序列如SEQID NO.4所示。2)序列表中所示与SEQ ID NO.2核酸序列具有同源性的INHBA-AS1(NR_027119)序列 SEQ ID NO.5，与SEQ ID NO.3核酸序列具有同源性的MIR4435-2HG(NR_024373)序列SEQ ID NO.6、MIR4435-2HG(NR_136161)序列SEQ ID NO.7、MIR4435-2HG(NR_136162)序列SEQ ID NO.8、MIR4435-2HG(NR_136163)序列SEQ ID NO.9、MIR4435-2HG(NR_136164)序列SEQ ID NO.10、MIR4435-2HG(NR_136165)序列SEQ ID NO.11、MIR4435-2HG(NR_136166)序列SEQ ID NO.12所示。在染色体上的同一基因由于转录方式以及转录后剪切加工等方式的不同可以生成高度同源的不同长度的RNA分子。本发明的的RNA分子SEQ IDNO.5是SEQ ID NO.2的同原序列，SEQ ID NO.6、SEQ ID NO.7、SEQ ID NO.8、SEQ ID NO.9、SEQ ID NO.10、SEQ ID NO.11、SEQ ID NO.12是SEQ ID NO.3同源序列。
本发明所述的RNA分子作为肿瘤标志物的应用，其特征在于，所述肿瘤为胃癌。
在研究过程中发明人发现，序列表中四种RNA分子SEQ ID NO.1、SEQ ID NO.2、SEQID NO.3、SEQ ID NO.4在胃癌组织中的表达比癌旁组织的表达高，同时发现这四个基因表达的RNA在胃癌患者血浆中的含量比健康人血浆中的含量高。由此可见，患者在患病期间这四种RNA表达的增加与胃癌存在着密切的相关性。本发明首次发现血浆/血清及组织中4个RNA基因，在胃癌临床早期诊断、鉴别诊断的作用，具有重大的理论意义和实用价值。
在上述发现的基础上，本发明提供了一组胃癌的RNA分子标志物，以及该分子标志物在制备诊断胃癌试剂中的应用。使用该分子标志物及含有该分子标志物的诊断试剂盒诊断胃癌，具有操作简单、取材方便的优点，且具有高特异性、高灵敏性和易于大量筛查的特点。
本发明提供的RNA分子标志物检测的方法，其包括测定离体样品中一种或多种RNA标志物的含量，其中所述一种或多种RNA标志物包括一种或多种选自序列表中的RNA标志物。在实际检测过程中，可以检测其中任一种RNA分子，也可以检测不同RNA分子的组合，确定胃癌患者样本中RNA分子含量是否相对于对照健康人群有所改变，由此进行胃癌的筛查和诊断。
本发明RNA分子检测方法所使用的样本可以是组织标本，同样也适用于体液样本，包括血浆、血清和尿液等。针对体液样本的无创诊断方式更具有临床应用价值。
本发明采用反转录实时定量PCR方法检测样本中的RNA分子。不同样本中RNA的制备均采用常规的RNA制备方法。
诊断胃癌的检测RNA分子系统中包括了常规的RNA反转录试剂、实时定量PCR试剂。其中包括了扩增RNA分子标志物的上、下游寡核苷酸引物。PCR扩增引物本领域人员均可以依照引物设计原则进行设计。本发明在实施例中优选了表1所示引物用于样本的检测分析，其中18s rRNA是作为内参分子。
表1. 实时定量PCR所用的引物序列
| RNA序列 | 上游引物（5′-3′） | 下游引物（5′-3′） |
| SEQ ID NO.1 | CTGCTTTGCCATTTCCCCTT | GTTGATGCCACACAGAGGGA |
| SEQ ID NO.2 | CCTACTACACACAGGGGCTC | TTCCAGAAGCTCCTCATGGG |
| SEQ ID NO.3 | AATTTGCCACCACCCTGTGA | ATGCCGTTTTAGGGGGACAG |
| SEQ ID NO.4 | TGCGTCCCTCGCATTCTTTA | GACAGGAGACACTTGAGGGC |
| 18S rRNA | GTAACCCGTTGAACCCCATT | CCATCCAATCGGTAGTAGCG |
为使本发明更易理解，下面结合具体实施例进一步阐述本发明，但下述实施例仅用于说明本发明而不用于限制本发明的范围，下列实施例中未提及的具体实验方法，通常按照常规实验方法进行。
结合附图说明本发明的具体实施方法。
附图说明
图1. NR_027119(A), NR_015395(B), NR_026887(C)和AK001058(D)在胃癌组织中的相对表达量。纵坐标是lncRNA的相对表达量（-△△Ct值）,横坐标是样本例数。
图2.胃癌患者及健康人群血浆中NR_027119(A), NR_015395(B), NR_026887(C)和AK001058(D)的相对表达量。纵坐标是lncRNA的相对表达量（△Ct值）,横坐标是不同类型样本。
图3. 4条lncRNA检测数据结果的ROC曲线分析及曲线下面积（AUC）（A），4条lncRNA联合ROC曲线分析及去除任何一条lncRNA后剩余3条lncRNA联合ROC曲线分析及曲线下面积（B）。横坐标是1-特异性（specificity），纵坐标是敏感度（sensitivity）。
实施例
实施例一
胃癌组织RNA检测
1. 组织样本RNA提取
49例配对的胃癌及癌旁组织手术切除标本用TRI试剂提取总RNA，用琼脂糖凝胶电泳检验组织中RNA的完整性。
2. RNA反转录
用ImProm II Reverse Transcriptase反应试剂盒进行逆转录反应。取1μg组织总RNA，作为反转录模板，加入1μL 随机引物、1μL dNTP（10mM）、5×RT buffer 4μL、 0.5μL RNase抑制剂、1μL ImProm II反转录酶，用无RNase水补齐至20μL。反应条件为：42℃ 60min，72℃15min，20℃ 5min。选择18S rRNA作为内参基因，组织反转录得到的cDNA，取1μL加9μL无RNase水稀释10倍，混匀后，取1μL稀释物加9μL无RNase水稀释10倍，第二次的稀释物作为胃癌及癌旁组织检测18S rRNA的模板。未稀释的cDNA作为检测AK001058、INHBA-AS1、MIR4435-2HG及CEBPA-AS1的模板。
3. 组织样本RNA分子检测
用SYBR Premix ExTaq试剂进行实时定量PCR，检测目的RNA分子在胃癌组织和癌旁组织中的相对表达量。以上述cDNA作为模板，分别使用表1中优选的PCR引物，用SYBR PremixExTaq试剂在MX3000P实时定量PCR仪上进行实时定量PCR，检测AK001058、INHBA-AS1、MIR4435-2HG及CEBPA-AS1等4个基因的相对表达量。实时定量PCR反应体系组分及用量：0.5μL cDNA模板、2×SYBR 10μL、PCR上游引物（20mM） 0.4μL、PCR下游引物（20mM）0.4μL、ROX0.4μL，加水补至20μL。反应条件为:先95℃ 30s预变性， 95℃ 10s变性，60℃延伸20s，45个循环。
检测结果见图1， INHBA-AS1（A）、MIR4435-2HG（B）、CEBPA-AS1（C）及AK001058（D）等4个基因在胃癌组织中的表达水平与配对胃癌旁组织中表达水平相比,显著上调,且p〈0.0001，有显著性差异。
实施例二
胃癌患者血浆RNA检测
1. 血浆RNA提取
51例胃癌患者血浆及53例性别、年龄匹配的正常人血浆用Qiagen血浆提取试剂盒提取200μL血浆中的总RNA，并溶于40μL无RNase水中。
2. RNA反转录
用ImProm II Reverse Transcriptase反应试剂盒进行逆转录反应。取10μL血浆总RNA分别作为反转录模板，加入1μL 随机引物、1μL dNTP（10mM）、5×RT buffer 4μL 、0.5μLRNase抑制剂、1μL ImProm II反转录酶，用无RNase水补齐至20μL。反应条件为：42℃60min，72℃ 15min，20℃ 5min。选择18S rRNA作为内参基因。血浆提取的RNA反转录得到的cDNA作为检测AK001058、INHBA-AS1、MIR4435-2HG、CEBPA-AS1及18S rRNA内参基因的模板。
3. 血浆样本RNA分子检测
用SYBR Premix ExTaq试剂进行实时定量PCR，检测目的RNA分子在胃癌组织和癌旁组织中的相对表达量。以上述cDNA作为模板，分别使用表1中优选的PCR引物，用SYBR PremixExTaq试剂在MX3000P实时定量PCR仪上进行实时定量PCR，检测AK001058、INHBA-AS1、MIR4435-2HG及CEBPA-AS1等4个基因的相对表达量。实时定量PCR反应体系组分及用量：0.8μL cDNA模板、2×SYBR 10μL、PCR上游引物（20mM） 0.4μL、PCR下游引物（20mM）0.4μL、ROX0.4μL、加水补至20μL。反应条件为:先95℃ 30s预变性， 95℃ 10s变性，60℃延伸20s，45个循环。
检测结果见图2， INHBA-AS1（A）、MIR4435-2HG（B）、CEBPA-AS1（C）及AK001058（D）等4个基因在胃癌患者血浆中的表达水平与在正常血浆中表达水平相比,显著上调,且p〈0.0001，有显著性差异。
4. ROC曲线分析
用SPSS17.0作ROC曲线并计算其AUC值、诊断指标的敏感度值及特异性值。将检测结果分成正常组及患病组，并将每组对应的数据录入SPSS17.0中。作ROC曲线，求对应的AUC值。根据计算出的每组敏感度值及（1-特异性）值求出cutoff值，cutoff值=敏感度+特异性-1，根据最大cutoff值即可计算出该诊断指标的敏感度值及特异性值。联合ROC分析：用二元logistic回归分析求出联合诊断指标的预测p值，然后根据预测p值作ROC曲线，并求出其AUC值及联合诊断指标的敏感度值及特异性值。
分析结果见图3，INHBA-AS1、MIR4435-2HG、CEBPA-AS1及AK001058等4个基因在胃癌患者血浆及正常人血浆中的相对表达量作ROC曲线，其曲线底下面积（AUC）分别0.855，0.882，0.785，0.852；上述4条基因联合ROC曲线分析得到的曲线底下面积（AUC）为0.921，分别剔除其中任意一条lncRNA，如INHBA-AS1、MIR4435-2HG、CEBPA-AS1或AK001058后，剩下3条lncRNA联合ROC曲线得到的曲线底下面积（AUC）分别为0.910、0.880、0.917及0.908。上述结果表明单一RNA分子和组合使用RNA分子均能作为胃癌诊断的RNA分子标志物。
序列表
<110> 中国人民解放军军事医学科学院放射与辐射医学研究所
<120> 一组胃癌RNA分子标志物及其应用
<160> 12
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uccauccaga aagacagaaa gccagaacau cuugaacagc ucuggugacu aucauauccu 840
uuucuucuaa gccaaauaug agauucuuuu auagcagcua ugacauucaa ggagcucuua 900
cagauguccc caauacuguc acaguggagu uuaucuuaca gaauugggcc acucuaagug 960
acuaccuguu gccucaaagg guaacagguc uaacagaaag aacuguacuc cagaauugua 1020
agucuucuag auucugcaac uggaagagua aguggauaag aauagccaag aacaugugaa 1080
agaagaauuu guggaaguua auuuguaaug aggacaauca uaaauucuuc cugaguuagg 1140
ucuccuuauc ugcaaaguuc ccaucugcca aggggacaag auacaacaug ggaaucccaa 1200
uggaugcaga agggaaguag agguaaauuu gccucuucua gccacacaau aucugguaga 1260
agaaacggag aaaaaggcag gggcagacaa ccagagggag ggguagugau ucuggggaaa 1320
acagaaggca gaguauauuc auuacaauuu aauaaaacua uaggagguga cccucuugaa 1380
ggcugccucc acacccacca gucaaggcuc caucaaugua aacuagcaau ccaacauggu 1440
agugcccaga gagccaagau uauuuaucau guuauggaca gauuggcaua ggcccugagg 1500
gguacucaaa ggccaguggg acugcuucaa ggcccuugug uugggguggu auccagcaua 1560
gcagacuccu cuagguugau auccugggcc agaggggaca gcuggacagu gucacauugg 1620
uucugacagg ugcauggcac uugcaugagc cagacugggg cuaagucagc caggcaggcu 1680
gucaggcccu aaucacauca aggauggcca aaucauguuc cacuagggac cagcuugagc 1740
ugcaaaugac caauaggaca aaugauguca uccagaggac ccaaccaccc ggaucugaga 1800
cacaguaagc cuccaucauc cacccagaca uacguuagga aacugaaaga ggaagacagg 1860
agccuccaaa gauuggguuu uuguguagaa ggaacugaau aauuuaaaga auguucaguu 1920
uaugagguca gacugagaug aaugaaugga gauaaggugu cacgaggaag aucagcucac 1980
ugagagcagu aguucucaac ccuggcugua cauugcccaa ugcccagagc uuucagaaaa 2040
uacucccccc caccccaaac cacaacuauu auguugcaau ugcugguggu gggcuuagau 2100
cugggcguag gugcauaugu augcaaggac acauauguac guaauuucuc caauguuuau 2160
aauguacaaa uaugaauuau cuaauagaaa uaaacagugu cacuaaaggg caugcccugg 2220
cagauccuca gggcuggugg aauuggcucc agaacuuuug cucuuggcuc ccauucccca 2280
cugggagaag ccugauaccu gacucccuga accuggccuu uggcuucaga cucugaaguc 2340
aaaucccuuc cuucucccuc uggcucaguc uccaucgacu caacuagucc ugccaccucu 2400
uuucugcuug gcccagcccu agcacccuac ucacuggugu agccauuaua ggcagcucaa 2460
uguagaccag ucagcguuuu ggcuggaaaa uagacagaug uagcugaaag aagcugaugg 2520
aucuuucuca ggacuggcag uuacccgcca ugaggaugaa ggccacaugg gguauaguca 2580
aggggugagc acacguccag ugaacuggcu gauuccugcu guggcaggug caaccugcag 2640
gcccacggau gucagaucuu cuacagaagg gaagccagaa uucuagauuu uuaucugaaa 2700
uuuaccaaua uuuaaauacc aguaaggaau ucauuuuuua uuacauugua ugugccaaau 2760
gaaaaauaaa ccuauuuaug aguuaguccc agccccaggc uccggccuug gccucuggaa 2820
agccucugaa acaguaggga uugcgggaag aagggugugu ggaggccaag gaucugcugc 2880
gccuuuccag ucaggugggu cacaaugaga ugguuaagug uuugagcaga cugugaccac 2940
acuaaaagug augcuucccc uggggcaguu uuacaauaaa gauaauaaaa accaa 2995
<210> SEQ ID NO.3
<211> 6137
<212> RNA
<213> 人
<400> SEQ ID NO.3
gccuccuucu ccuggugucc auuucuggaa cugcuauuug uauauugcau gauauuuuau 60
caggaaaaaa uauaaaacag aucuaauuuc augaaaaugc uguugccaua augcucagga 120
gaacaggggg aagagagaga uucaagucuu ccuaaugucu accuuauaug cagagccuug 180
gaaagauggg caaaugcucu gugacaagcc accaggguag acugguacug aaaagacccu 240
acuacacaca ggggcucugu cccuggcugg aaaguuacaa gucagccuac cucucuguga 300
ucugguuucc acaccuacua cucuuuaucc caugaggagc uucuggaaac uaaaauaggu 360
acuucgaauu ucauuguugc aucgagccag cugauuuggg aguugaguuc cuggauaggc 420
auacuaucca caguguuuua ccagagugaa aucacaggau aggcucagcu guaacaaacu 480
auaucaaauc ucagaagcuu caaaagacua agguuuauuu cucacucaug ccacccgucu 540
acugaggguc augcggaguu cugcugagug auguucucca uccaggaucc cagccaggau 600
cccagcuggu agagcagccu ccaccuggaa cauugccuaa gauauuggaa ggguacacca 660
aggcaauggu gaagcucaaa guggcuccua auggcuggcc agaaucagcc uuuguaucuc 720
cuuggccaaa gcaagucuca ugaccacagc uaauucccag caggugaaga ugugauuucu 780
uccauccaga aagacagaaa gccagaacau cuugaacagc ucuggugacu aucauauccu 840
uuucuucuaa gccaaauaug agauucuuuu auagcagcua ugacauucaa ggagcucuua 900
cagauguccc caauacuguc acaguggagu uuaucuuaca gaauugggcc acucuaagug 960
acuaccuguu gccucaaagg guaacagguc uaacagaaag aacuguacuc cagaauugua 1020
agucuucuag auucugcaac uggaagagua aguggauaag aauagccaag aacaugugaa 1080
agaagaauuu guggaaguua auuuguaaug aggacaauca uaaauucuuc cugaguuagg 1140
ucuccuuauc ugcaaaguuc ccaucugcca aggggacaag auacaacaug ggaaucccaa 1200
uggaugcaga agggaaguag agguaaauuu gccucuucua gccacacaau aucugguaga 1260
agaaacggag aaaaaggcag gggcagacaa ccagagggag ggguagugau ucuggggaaa 1320
acagaaggca gaguauauuc auuacaauuu aauaaaacua uaggagguga cccucuugaa 1380
ggcugccucc acacccacca gucaaggcuc caucaaugua aacuagcaau ccaacauggu 1440
agugcccaga gagccaagau uauuuaucau guuauggaca gauuggcaua ggcccugagg 1500
gguacucaaa ggccaguggg acugcuucaa ggcccuugug uugggguggu auccagcaua 1560
gcagacuccu cuagguugau auccugggcc agaggggaca gcuggacagu gucacauugg 1620
uucugacagg ugcauggcac uugcaugagc cagacugggg cuaagucagc caggcaggcu 1680
gucaggcccu aaucacauca aggauggcca aaucauguuc cacuagggac cagcuugagc 1740
ugcaaaugac caauaggaca aaugauguca uccagaggac ccaaccaccc ggaucugaga 1800
cacaguaagc cuccaucauc cacccagaca uacguuagga aacugaaaga ggaagacagg 1860
agccuccaaa gauuggguuu uuguguagaa ggaacugaau aauuuaaaga auguucaguu 1920
uaugagguca gacugagaug aaugaaugga gauaaggugu cacgaggaag aucagcucac 1980
ugagagcagu aguucucaac ccuggcugua cauugcccaa ugcccagagc uuucagaaaa 2040
uacucccccc caccccaaac cacaacuauu auguugcaau ugcugguggu gggcuuagau 2100
cugggcguag gugcauaugu augcaaggac acauauguac guaauuucuc caauguuuau 2160
aauguacaaa uaugaauuau cuaauagaaa uaaacagugu cacuaaaggg caugcccugg 2220
cagauccuca gggcuggugg aauuggcucc acaaguauga agagaauguc gggagaggaa 2280
gugguggcua ugagucagca ugagucaucu cguuccaaug agaaugaagg cugaggugug 2340
cgccuuuuuu uuuuuuccuu cuuagucgug uguacaucau ugggaaugga gggaaauaaa 2400
ugacuggaug gucgcugcuu uuuaaguuuc aaauugacau uccagacaag cggugccuga 2460
gcccgugccu gucuucagau cuucacagca caguuccugg gaagguggag ccaccagccu 2520
cucccugaca agcaaagugg aucagcaaag gcugcaguca ccagcaucuu uuccaaccuu 2580
aaugaacugu auccucaaaa gaacacuauc agacugguaa gacaagcauu auugucccac 2640
uucacagaug aagagcuugg gggcccugug gauguguagg agagucggcc uuccuuuuua 2700
uaggccuuuu gcugagcuca gaggacagag cagaagacaa agccgaaugc agcccuaagc 2760
agacacuauc ccagcccaag gagcuaugca gacagcuccu gccuagagga gaaacaauuc 2820
ucuccuucag ccaggcaugu ggcacagagg ugaacaggaa augcuuaggg agacaguuca 2880
cagauauaua uguacuucac agggcacaau uuaauccaua aaucaaucau ggaucaccgc 2940
uaaagaaaac aaaauaugcu gccacuaauu ugccaccacc cugugagcau gauuggauga 3000
uguuuauuuu gauuaggaga uugcuccauu uauaaaucuu caauacaucc ugucccccua 3060
aaacggcauc ugggucuuuu gaggguuaaa aaaaaaaaaa agugaaauug gaugagggau 3120
gagagcugga cuucugugug ucccgggguc ccuggaucca cagccuggug ccuagcauca 3180
guuaagccca cgcugggguc gcaucacauc ccgcaaagcc acgugcucug ugaggccaac 3240
aggagccccg ccggguggac cagcuggaau cucagagagc gccgacucug aaacuacccg 3300
gcucugcaga agcacgcugg gcccaggggc uucuagacug acagcuccau uuaucaacua 3360
ccuauugguu uuaaaaauug gagugucuuu uccgcguuga cugauuuugg cucuaagaga 3420
ugucgcuggu cauuucagag ugacugaacc uccccucuaa cagaucccgg gaauuguuuu 3480
caggaaaggu aaaaggcagc cuuuucuguc acaacacaac gcugagccgg cagccuggcu 3540
cugucaggau cuggggcucc cgcgcccgag aagcccagcc ucgccggcgg ccaaguucac 3600
cgcgaggccc cgcgcugccu gcgcugcgcu cccggacccg caccgaccgc agcgcgcgcc 3660
gccggugcuu cucccacccc agccuggaag cugccucccu ccgccuaugc cugcaggaua 3720
agaagcccga ggaggcggag cauggaacuc gacaguuaaa acauuuaaga gagaaaaccu 3780
agugucuugc uggccugaaa ucgaguacgc agcccggggu gaucaggguc ucccggcccg 3840
gaugugugag acuugcuucc ccugggcaau aggcgauacg augcuuuagg aggaaggugu 3900
cucucccucc uaagccccgg aggggagaac uuccaaagac agaaaaccac aggcuuccug 3960
gcacagagcu uucccuuuau cagcuaaagc agaaucuuuu cuggccuuaa ccuggccccu 4020
uccucuaacu gcaggcagag aggcagacag aaaagcacuu gcugaaacac aaaguuuugu 4080
ucuguccuca acgaacuguc uagagcugau ugcugauagu cguggugcau uaugccuucc 4140
ugguuuucau uuaauugggc accacgcugc cuuucaagac gccuuaaagg aaccaacaac 4200
caaauccaag agagcuggac agaccauuga acacacagua ggcugugucu cguggcuuuc 4260
guugucuggu gccucaaaga aaacaccaga aagauuguuu cuaagcuaga gccaccccag 4320
auugcuuaaa gugcaaagcu cacugcuguu ggggguaccc uugugagaca cuggaaagcu 4380
gguuuuaccg uggcccuaug aagaggaaga cugaaauuua gacaguaaua ccuuuacuag 4440
gauuggaaaa gauuugguua augacagccc ugucauuucu aaaacccauu aucacuguau 4500
gagagauucc uuugcgcugc auccucgaca gugcuuccua aggcucugcc gacuuccagu 4560
ucuggaacaa gaugguuaaa cucauuuuuc ccugcucugc uccucuaaau acaacuaagu 4620
accuuggaaa cuauucagca gacaaugaua aagggcucug aaagcuagaa gaaaaggugu 4680
acuugcaaga aaccucagga cuugaguaac agcaacauga acaauccauu ucacagauga 4740
agaaacagac ucagugagca cgugaucacu ucucacaacu aauggagcca agauucuguc 4800
cuuauggcuc cagagaccuc uuuuuuuucc cacuguacca caacacucac caggacugga 4860
gugccaccua ugaccucauu gcauaaugga uggcuugucc ucaaaugggc ccggucuugg 4920
acgagccuga ggaugucuac aaguggaaga aaagaagcca cuggagcaga agguggggag 4980
gauaaaauuu ggagcaagau ucucaaggaa gcaacaagau ccuaagaucu uguucucacu 5040
agagaauaau uucuacauua ugcccagguu cuucugagcu augaaggggc ccagauuuaa 5100
gggcuauuuu ugacacccua aaugugcuga gacaagucau uaaggugguc cugccaggac 5160
acagccaucu aaagcagcaa ucugcuucuu gccagaaaau cucgugccuc ugcagagccu 5220
uuuccagaau gaaccacacc augcugagga aaggagaaag agacuaccua cugcauuucu 5280
gucacucgcu gaaaaggaca cucugucaga aaaucuucua gcaaacuuca aagggcaaaa 5340
ucaccccuug uuacugauaa agcccagaga gcuucagcag cuaacauucc cuggacaggg 5400
cacagcaagg auuugaaccu aggucagucu ggccagaaca cccacaagcu uuccuuaacu 5460
cagugugcua ucuccccacg acuaggucac uacugcuuua uaaucaccuu uguagccacc 5520
aguggauuuu gcucaucagu auuuuucagg caauugauac uuuagauauu cagcugcaag 5580
acguaugcag uuuucauuga caucuuuugg agaaacugac aaaccuggac uugacuuaau 5640
gccuuuggaa ccuuccaaga uguuauauaa cucuagauag aaggcugggc cuccaugaug 5700
ucaggaaugu ugcauucuua uuuccccaua gauaaaccca uuuguccaca aagucaagga 5760
gucaggcaga ggcccuugcc auggggcuuu uuaggauaaa gcaacaagcc uggacuuugc 5820
ucuacaacag gguuuugcau agggaguggu augaccagau cccucaagaa agaaagcuua 5880
gagaccaggc cagaguccac ugcaguagcc cagucaagag aggaugguga cuuggacuug 5940
uaguagagcc aguuagaaug aaagaaauug acacauucag aaaugguuuu agagauagag 6000
ucaaacugga ccugauaaag aacuagagaa gcggagugag gauaaagaga agagccauga 6060
cugacucgga agauuuuguc uugaaaaacu ugagaacuca agacagagug aaauaaaauc 6120
acauguggga aaaaucu 6137
<210> SEQ ID NO.4
<211> 2281
<212> RNA
<213> 人
<400> SEQ ID NO.4
cacggccggg agcccaggag uaucccgagg cugcacgggg uagggguggg gggcggaggg 60
cgagucuugg ucuugagcug cuggggcgcg gauucucuuu caaagccaga accaggccug 120
ucccggaccc gcgucccggg gaggcugcag cgcagagcag cggggcuggg gccggugggg 180
ggccguuugg gacgcgcgga gagguccuga gcgcgguggc ucugcgucuc cuagcucuga 240
ucuccaggcu accccuguga uuccgcgcag agguaccucu cggaggacgc cgggguccca 300
ugggcggcgc cgcgcagggc gcuaggaccc cgcggggagc ggaggcggcc ucggcccggg 360
agccuggagg accuggccgg ucgauccgcc cgggcuggaa aacuuucuuu auaauuacuu 420
cuccaggucg gagcgcgcgg cuugcuaggc gcgcggggcc ggcgcuguua cccggcgugg 480
agucgccgau uuuuuuuccu gcgggaccgc ggggcccccc agacuagcgg agcuggacgc 540
cggggcgagc acggggaggg gcgcaccgag ggaggagaca aacuuaacuc uggggccggg 600
auuccgaggc gggggccgca gcccucgagg cccgaagcca ccgcuuccuc ccccgccucc 660
ccauucaggu gggcgccaac ggcgggagcg agggugucca ggccgccggg cugccagguc 720
cgagcacgca cagggagaac ucugcccagu gguucgccgg gcgcuguagu ccccgggauc 780
cuagggaccg aggcggccag gcccuggggc cccuugagug cggcagcuaa ugcucucacc 840
gcggcggggg aaggagcuug ccaccgagac ccccagccac gugcgucccu cgcauucuuu 900
accggggccg ggguggcggc uacggaccgu cagcugggcc cagauggagu cuugggagcc 960
cucaaguguc uccuguccuu gcccgcgccg ccccucgcca cuggcgcuga ggccugacgc 1020
cgccugcguc ccggcuagag gcgcgcuugc cuacagguga gggaagaccc ccuucaccga 1080
caguggccuu aggccuggca aggcgccacg acccgcccag gagccccgga gggggcacag 1140
cuaaaaacac cgcuggagag ccccgagcuu ccacgacgau cgcaguaaag aagcaguuuc 1200
aucugggcaa cgcacacugc gcuuuaauca aguuccuauu caacauaguc ccagugauua 1260
auagcccaac ugcuucguuu ucgguccaga gcucauaaac aagauauuuu uagcuugacg 1320
cuuuuggacg ggagggagua aaaaccagau acguuaaaua aauaucccga ugugagccgg 1380
agagcugcuu gcugagccaa augcaggacc cauucauaua gcauucaccu guggagggag 1440
accuggacgg aaaucaaaaa gcaccaagag cgauuugcgu uuuuuucugc ggugcuaaaa 1500
cuaauggcuu uuccuaccua ggaacaaaga aacgccacug uacaugcacg guucccggcc 1560
uguggaguug ugggaggaag gcgaugucug gccuuuuuug cacagcugcu guugccugcc 1620
cagagaucgg gaacucugcc ccguaggacu ggaagaaacc ucaguaaugg gaauaagacu 1680
uuguccaaua gggggcugau gaaugugugg gggcgacaau ggcaaggagu gggacucccg 1740
gcccgggguu cgccaacccc aggggccaca gguccuccua caauugaacc agaauucacc 1800
cacccgggcc ugcccugugc agggugccga gagcccaggg augcaugaga ggguggcucc 1860
ugccucuggg aacugggaca gugggagaga cggauaaguu gucacacaga ggcugcuggg 1920
aggaaggagg agacagaagg aguaggggau gggacuucau ucauucauca aaugcacacg 1980
aggcacaaau gggaaucaag gguggaugug cugugaugaa gagaaguccu gcccugaaca 2040
agguggcgcu guggaggagg cagagaucag auuugucugc ggagguguua uggacugaac 2100
ugugucccug ccccaaauuc cuauguugaa ggccuaaccc ccaugugacu guauuuggag 2160
auaaggcuuu uaggaaguca uuaaagugag augaugucau aaaaaaaaaa aaaaaaaaaa 2220
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2280
a 2281
<210> SEQ ID NO.5
<211> 1858
<212> RNA
<213> 人
<400> SEQ ID NO.5
gcuauuugua uauugcauga uauuuuauca ggaaaaaaua uaaaacagau cuaauuucau 60
gaaaaugcug uugccauaau gcucaggaga acagggggaa gagagagauu caagucuucc 120
uaaugucuac cuuauaugca gagccuugga aagaugggca aaugcucugu gacaagccac 180
caggguagac ugguacugaa aagacccuac uacacacagg ggcucugucc cuggcuggaa 240
aguuacaagu cagccuaccu cucugugauc ugguuuccac accuacuacu cuuuauccca 300
ugaggagcuu cuggaaacua aaauagcagc ugcccaggua gaagaguguu gaccaaagga 360
cacaucacca gcacagacug uuaaucaugu gacuagagaa aacucucaug guggcauuca 420
aauuuccaua uccuucuucu auggaaauuu cugagagacc cagaaaagaa gcguaacgac 480
gagggaaagu gauuccugca gaccugaaca uuccagacuu accaggugau ccagcugucu 540
gucagcggga agaggcugag gcgcccccuu cuggugcauc ugaauaguaa gaaacccugu 600
guagaaagaa acccuguagc aauugggcac cuucuccgug aucugucugc uuccaauacc 660
aaaaauuguu gcuuuuuaaa ugacauccau ccuaagcuua aaaaagacgc auauuauuug 720
uauaaaaugu ugaagacgca gaacaaaaaa uguaaaucac auguaaucau cccuuccaga 780
aauaaucguu auuaaaauuu cuguguaugu guaaaaaaaa aaauugcaau ccuacuguaa 840
uauaauccug uauacugaua uuuuucaccu aucacuguau guugagcauu uucaauaguc 900
aaauuauuuc uugaaaauau uaaugacugg ggaguaaccu uucaaauagg ugugucuuua 960
uuuuuaaacc aguccacaau uauuguauau ugaagucauu ucccaaauuu uguaaguaua 1020
aguauugcau ccauccuuau auguauuuaa augcaucucu uauuauuucc uugagauaag 1080
uuccuagaag uggaaucacu ggauuuaaaa auguggacau auuuaugcca gacgcggugg 1140
gucaugccug uaaucccagc acuuugggag acugaagcag guggaucacu ugaggucagg 1200
aguucaagac cagccuggcc aacauaguga aaccccaucu cuacuaaaau uacaaaaauu 1260
agccgggugu gguagugcac gccuguaauc ccagcuacuc aggaggcuga ggcauaagaa 1320
ucacuugaac ucaggaggcg gagguugcag ugagccaaga uggcaccacu gcgcuccagu 1380
cugggcgaca gaguaagacu ucaucucaaa aauaaauaaa uaaaauuaaa auuaaauaag 1440
auaaauaaaa aauaaaaaug uggacauauu uaaaucuuca uauauauuac caaaugcccu 1500
ccugaaaguu uuuaccuguu acauuccaac caauagugua agggcaugac ucuuucccug 1560
uguuuuggga uggauguuau caaaguucuc ucccacccag gccaaguaug guauaugcuu 1620
ugauuuaauu ugaauuuuua aauuauuauu uaaaauggac auuuuguugu ccauuugaac 1680
aacuuucuuu ugagucacug uucauguucu uugcccauug uuucucuuuu auuaguaaga 1740
acccuauugu cauuuuuaua uuuuaaauaa aauuucauug uauauacauu uauauuaucu 1800
auaguaaagu auauuuuauu auuaaugaga acuuuuuaua uuaaagaucc uaaccuac 1858
<210> SEQ ID NO.6
<211> 603
<212> RNA
<213> 人
<400> SEQ ID NO.6
acaaguauga agagaauguc gggagaggaa gugguggcua ugagucagca ugagucaucu 60
cguuccaaug agaaugaagg cugaggugug cgccuuuuuu uuuuuuccuu cuuagucgug 120
uguacaucau ugggaaugga gggaaauaaa ugacuggaug gucgcugcuu uuuaaguuuc 180
aaauugacau uccagacaag cggugccuga gcccgugccu gucuucagau cuucacagca 240
caguuccugg gaagguggag ccaccagccu cucccugaau aacugggaga ugaaacagga 300
agcucuauga cacacuugau cgaauaugac agacacugaa aaucacgacu caucccccuc 360
cagcaccucu accuguugcc cgccgaucac agccggaaug cagcugaaag auucccuggg 420
gccugguucc aacugcccac uguggacucu gaggccucug cauuugcggg uggucugccu 480
gugauauuuu ggucaugggc uggucugguc gguuucccau uugucuggcc agucucugug 540
ugucuuaauc ccuuguccuu cauuaaaagc aaaacuaaag aaaacagaaa aaaaaaaaaa 600
aaa 603
<210> SEQ ID NO.7
<211> 1655
<212> RNA
<213> 人
<400> SEQ ID NO.7
acaaguauga agagaauguc gggagaggaa gugguggcua ugagucagca ugagucaucu 60
cguuccaaug agaaugaagg cugaggugug cgccuuuuuu uuuuuuccuu cuuagucgug 120
uguacaucau ugggaaugga gggaaauaaa ugacuggaug gucgcugcuu uuuaaguuuc 180
aaauugacau uccagacaag cggugccuga gcccgugccu gucuucagau cuucacagca 240
caguuccugg gaagguggag ccaccagccu cucccugaca agcaaagugg aucagcaaag 300
gcugcaguca ccagcaucuu uuccaaccuu aaugaacugu auccucaaaa gaacacuauc 360
agacuggcuc ugccgacuuc caguucugga acaagauggu uaaacucauu uuucccugcu 420
cugcuccucu aaauacaacu aaguaccuug gaaacuauuc agcagacaau gauaaagggc 480
ucugaaagcu agaagaaaag guguacuugc aagaaaccuc aggacuugag uaacagcaac 540
auggcaggcc agaaagcaga cccagggagg auagcacaug ucuucggcua cacuggugaa 600
ggcaucgugc cugcuccaca gcacauuuuu auucaagucu uggacgagcc ugaggauguc 660
uacaagugga agaaaagaag ccacuggagc agaagguggg gaggauaaaa uuuggagcaa 720
gauucucaag gaagcaacaa gauccuaagg aaaggagaaa gagacuaccu acugcauuuc 780
ugucacucgc ugaaaaggac acucugucag aaaaucuucu agcaaacuuc aaagggcaaa 840
aucaccccuu guuacugaua aagcccagag agcuucagca gcuaacauuc ccuggacagg 900
gcacagcaag gauuugaacc uaggucaguc uggccagaac acccacaagc uuuccuuaac 960
ucagugugcu aucuccccac gacuagguca cuacugcuuu auaaucaccu uuguagccac 1020
caguggauuu ugcucaucag uauuuuucag gcaauugaua cuuuagauau ucagcugcaa 1080
gacguaugca guuuucauug acaucuuuug gagaaacuga caaaccugga cuugacuuaa 1140
ugccuuugga accuuccaag auguuauaua acucuagaua gaaggcuggg ccuccaugau 1200
gucaggaaug uugcauucuu auuuccccau agauaaaccc auuuguccac aaagucaagg 1260
agucaggcag aggcccuugc cauggggcuu uuuaggauaa agcaacaagc cuggacuuug 1320
cucuacaaca ggguuuugca uagggagugg uaugaccaga ucccucaaga aagaaagcuu 1380
agagaccagg ccagagucca cugcaguagc ccagucaaga gaggauggug acuuggacuu 1440
guaguagagc caguuagaau gaaagaaauu gacacauuca gaaaugguuu uagagauaga 1500
gucaaacugg accugauaaa gaacuagaga agcggaguga ggauaaagag aagagccaug 1560
acugacucgg aagauuuugu cuugaaaaac uugagaacuc aagacagagu gaaauaaaau 1620
cacauguggg aaaaaucuaa aaaaaaaaaa aaaaa 1655
<210> SEQ ID NO.8
<211> 3910
<212> RNA
<213> 人
<400> SEQ ID NO.8
acaaguauga agagaauguc gggagaggaa gugguggcua ugagucagca ugagucaucu 60
cguuccaaug agaaugaagg cugaggugug cgccuuuuuu uuuuuuccuu cuuagucgug 120
uguacaucau ugggaaugga gggaaauaaa ugacuggaug gucgcugcuu uuuaaguuuc 180
aaauugacau uccagacaag cggugccuga gcccgugccu gucuucagau cuucacagca 240
caguuccugg gaagguggag ccaccagccu cucccugaca agcaaagugg aucagcaaag 300
gcugcaguca ccagcaucuu uuccaaccuu aaugaacugu auccucaaaa gaacacuauc 360
agacugguaa gacaagcauu auugucccac uucacagaug aagagcuugg gggcccugug 420
gauguguagg agagucggcc uuccuuuuua uaggccuuuu gcugagcuca gaggacagag 480
cagaagacaa agccgaaugc agcccuaagc agacacuauc ccagcccaag gagcuaugca 540
gacagcuccu gccuagagga gaaacaauuc ucuccuucag ccaggcaugu ggcacagagg 600
ugaacaggaa augcuuaggg agacaguuca cagauauaua uguacuucac agggcacaau 660
uuaauccaua aaucaaucau ggaucaccgc uaaagaaaac aaaauaugcu gccacuaauu 720
ugccaccacc cugugagcau gauuggauga uguuuauuuu gauuaggaga uugcuccauu 780
uauaaaucuu caauacaucc ugucccccua aaacggcauc ugggucuuuu gaggguuaaa 840
aaaaaaaaaa agugaaauug gaugagggau gagagcugga cuucugugug ucccgggguc 900
ccuggaucca cagccuggug ccuagcauca guuaagccca cgcugggguc gcaucacauc 960
ccgcaaagcc acgugcucug ugaggccaac aggagccccg ccggguggac cagcuggaau 1020
cucagagagc gccgacucug aaacuacccg gcucugcaga agcacgcugg gcccaggggc 1080
uucuagacug acagcuccau uuaucaacua ccuauugguu uuaaaaauug gagugucuuu 1140
uccgcguuga cugauuuugg cucuaagaga ugucgcuggu cauuucagag ugacugaacc 1200
uccccucuaa cagaucccgg gaauuguuuu caggaaaggu aaaaggcagc cuuuucuguc 1260
acaacacaac gcugagccgg cagccuggcu cugucaggau cuggggcucc cgcgcccgag 1320
aagcccagcc ucgccggcgg ccaaguucac cgcgaggccc cgcgcugccu gcgcugcgcu 1380
cccggacccg caccgaccgc agcgcgcgcc gccggugcuu cucccacccc agccuggaag 1440
cugccucccu ccgccuaugc cugcaggaua agaagcccga ggaggcggag cauggaacuc 1500
gacaguuaaa acauuuaaga gagaaaaccu agugucuugc uggccugaaa ucgaguacgc 1560
agcccggggu gaucaggguc ucccggcccg gaugugugag acuugcuucc ccugggcaau 1620
aggcgauacg augcuuuagg aggaaggugu cucucccucc uaagccccgg aggggagaac 1680
uuccaaagac agaaaaccac aggcuuccug gcacagagcu uucccuuuau cagcuaaagc 1740
agaaucuuuu cuggccuuaa ccuggccccu uccucuaacu gcaggcagag aggcagacag 1800
aaaagcacuu gcugaaacac aaaguuuugu ucuguccuca acgaacuguc uagagcugau 1860
ugcugauagu cguggugcau uaugccuucc ugguuuucau uuaauugggc accacgcugc 1920
cuuucaagac gccuuaaagg aaccaacaac caaauccaag agagcuggac agaccauuga 1980
acacacagua ggcugugucu cguggcuuuc guugucuggu gccucaaaga aaacaccaga 2040
aagauuguuu cuaagcuaga gccaccccag auugcuuaaa gugcaaagcu cacugcuguu 2100
ggggguaccc uugugagaca cuggaaagcu gguuuuaccg uggcccuaug aagaggaaga 2160
cugaaauuua gacaguaaua ccuuuacuag gauuggaaaa gauuugguua augacagccc 2220
ugucauuucu aaaacccauu aucacuguau gagagauucc uuugcgcugc auccucgaca 2280
gugcuuccua aggcucugcc gacuuccagu ucuggaacaa gaugguuaaa cucauuuuuc 2340
ccugcucugc uccucuaaau acaacuaagu accuuggaaa cuauucagca gacaaugaua 2400
aagggcucug aaagcuagaa gaaaaggugu acuugcaaga aaccucagga cuugaguaac 2460
agcaacaugu cuuggacgag ccugaggaug ucuacaagug gaagaaaaga agccacugga 2520
gcagaaggug gggaggauaa aauuuggagc aagauucuca aggaagcaac aagauccuaa 2580
gcucaccaag cuccuguauc uacuggaaaa uggaagucca gccuuaccaa cuugugaacc 2640
uugucugaag ggagccaggg ccugccaaug gaaccaccuc caggagcugc aacugcuguu 2700
gucauuaaua ccauuguguc uauuuuuuga gagagauaaa cuuuucaugg uguuacauuu 2760
uggaaaaaaa aaaaaaagac uaggugaaca gucagguagg aaagcagcau aacagucccu 2820
uaaauucuga ucauguagga cauucuucuu ugcccugggc cugggaaaau gcagcauguu 2880
ccagagcaaa aguccuaaug aggggaacua aaccaguggg acccaaacca auguccuggc 2940
ucacugagga cccguuagaa ccaaaucucu ggguguggac aggcucccau acuuuucaaa 3000
aauuccccug augacuaaug aacaaccaga gguaagaacc aguggcccag aggaauaacc 3060
agcccagcug uuguacgagc ucgcuaagcu ggcucagguc aauguugaau ucucugcuag 3120
gcagcuccuc auaagaacug gcagagaugg uucuuacaca acaacaggug acaacuccag 3180
acucugccgg aaguuccagg aucuggguuc ccggacaaug caugacacuc aguccagcau 3240
ugcaggugga agagcgacgg ugaaaagacc aaagucaauu aaaauguguu aaccaaaaca 3300
ggaaacauga gugaggugau ugagagugug uuuaacuuag augugugauu uuaucaauac 3360
uuucauuguu caaaaacucu uauuuuuuaa agauauuuuc aaaacaaauc caaacuuuac 3420
uuuucauucc aaauucgugu uccgucuaua cuugcauuug gggaaagauu gaaacaaaac 3480
acaaauacuu uguagcaaug uuggaguguc auguucuuug cagagggaca ggaaaaaaaa 3540
aggauuuuuu uuucuuauca agagauacug uuuccucaag gagaaagggc aucaguccaa 3600
ggcacugguu ugcucaaaaa gauuaguaaa gaacaagcau auuuugucug uggugacaac 3660
augaucuccc cccccccacu aguaaacuca cagcaucagu acgcaggcag ugugaugcau 3720
uuucaaaguu ccucacuuuu ccagauccaa caggacucuu gugcacauac ucgguguuuc 3780
cauggcaaau ccacugugua ugaaaauuag acccuuccaa aaaacaaauu uacuagucag 3840
uaaccaucau cagcacuuuu uuucuguacc augaaauuug ggaacaaaau uaaagggcuc 3900
uugauugaaa 3910
<210> SEQ ID NO.9
<211> 2273
<212> RNA
<213> 人
<400> SEQ ID NO.9
acaaguauga agagaauguc gggagaggaa gugguggcua ugagucagca ugagucaucu 60
cguuccaaug agaaugaagg cugaggugug cgccuuuuuu uuuuuuccuu cuuagucgug 120
uguacaucau ugggaaugga gggaaauaaa ugacuggaug gucgcugcuu uuuaaguuuc 180
aaauugacau uccagacaag cggugccuga gcccgugccu gucuucagau cuucacagca 240
caguuccugg gaagguggag ccaccagccu cucccugaca agcaaagugg aucagcaaag 300
gcugcaguca ccagcaucuu uuccaaccuu aaugaacugu auccucaaaa gaacacuauc 360
agacuggcuc ugccgacuuc caguucugga acaagauggu uaaacucauu uuucccugcu 420
cugcuccucu aaauacaacu aaguaccuug gaaacuauuc agcagacaau gauaaagggc 480
ucugaaagcu agaagaaaag guguacuugc aagaaaccuc aggacuugag uaacagcaac 540
auggcaggcc agaaagcaga cccagggagg auagcacaug ucuucggcua cacuggugaa 600
ggcaucgugc cugcuccaca gcacauuuuu auucaagaac aauccauuuc acagaugaag 660
aaacagacuc agugagcacg ugaucacuuc ucacaacuaa uggagccaag auucuguccu 720
uauggcucca gagaccucuu uuuuuuccca cuguaccaca acacucacca ggacuggagu 780
gccaccuaug accucauugc auaauggaug gcuuguccuc aaaugggccc ggucuuggac 840
gagccugagg augucuacaa guggaagaaa agaagccacu ggagcagaag guggggagga 900
uaaaauuugg agcaagauuc ucaaggaagc aacaagaucc uaagcucacc aagcuccugu 960
aucuacugga aaauggaagu ccagccuuac caacuuguga accuugucug aagggagcca 1020
gggccugcca auggaaccac cuccaggagc ugcaacugcu guugucauua auaccauugu 1080
gucuauuuuu ugagagagau aaacuuuuca ugguguuaca uuuuggaaaa aaaaaaaaaa 1140
gacuagguga acagucaggu aggaaagcag cauaacaguc ccuuaaauuc ugaucaugua 1200
ggacauucuu cuuugcccug ggccugggaa aaugcagcau guuccagagc aaaaguccua 1260
augaggggaa cuaaaccagu gggacccaaa ccaauguccu ggcucacuga ggacccguua 1320
gaaccaaauc ucugggugug gacaggcucc cauacuuuuc aaaaauuccc cugaugacua 1380
augaacaacc agagguaaga accaguggcc cagaggaaua accagcccag cuguuguacg 1440
agcucgcuaa gcuggcucag gucaauguug aauucucugc uaggcagcuc cucauaagaa 1500
cuggcagaga ugguucuuac acaacaacag gugacaacuc cagacucugc cggaaguucc 1560
aggaucuggg uucccggaca augcaugaca cucaguccag cauugcaggu ggaagagcga 1620
cggugaaaag accaaaguca auuaaaaugu guuaaccaaa acaggaaaca ugagugaggu 1680
gauugagagu guguuuaacu uagaugugug auuuuaucaa uacuuucauu guucaaaaac 1740
ucuuauuuuu uaaagauauu uucaaaacaa auccaaacuu uacuuuucau uccaaauucg 1800
uguuccgucu auacuugcau uuggggaaag auugaaacaa aacacaaaua cuuuguagca 1860
auguuggagu gucauguucu uugcagaggg acaggaaaaa aaaaggauuu uuuuuucuua 1920
ucaagagaua cuguuuccuc aaggagaaag ggcaucaguc caaggcacug guuugcucaa 1980
aaagauuagu aaagaacaag cauauuuugu cuguggugac aacaugaucu cccccccccc 2040
acuaguaaac ucacagcauc aguacgcagg cagugugaug cauuuucaaa guuccucacu 2100
uuuccagauc caacaggacu cuugugcaca uacucggugu uuccauggca aauccacugu 2160
guaugaaaau uagacccuuc caaaaaacaa auuuacuagu caguaaccau caucagcacu 2220
uuuuuucugu accaugaaau uugggaacaa aauuaaaggg cucuugauug aaa 2273
<210> SEQ ID NO.10
<211> 2046
<212> RNA
<213> 人
<400> SEQ ID NO.10
acaaguauga agagaauguc gggagaggaa gugguggcua ugagucagca ugagucaucu 60
cguuccaaug agaaugaagg cugaggugug cgccuuuuuu uuuuuuccuu cuuagucgug 120
uguacaucau ugggaaugga gggaaauaaa ugacuggaug gucgcugcuu uuuaaguuuc 180
aaauugacau uccagacaag cggugccuga gcccgugccu gucuucagau cuucacagca 240
caguuccugg gaagguggag ccaccagccu cucccugaca agcaaagugg aucagcaaag 300
gcugcaguca ccagcaucuu uuccaaccuu aaugaacugu auccucaaaa gaacacuauc 360
agacuggcuc ugccgacuuc caguucugga acaagauggu uaaacucauu uuucccugcu 420
cugcuccucu aaauacaacu aaguaccuug gaaacuauuc agcagacaau gauaaagggc 480
ucugaaagcu agaagaaaag guguacuugc aagaaaccuc aggacuugag uaacagcaac 540
auggaaagga gaaagagacu accuacugca uuucugucac ucgcugaaaa ggacacucug 600
ucagaaaauc uucuagcaaa cuucaaaggg caaaaucacc ccuuguuacu gauaaagccc 660
agagagcuuc agcagcuaac auucccugga cagggcacag caaggauuug aaccuagcuc 720
accaagcucc uguaucuacu ggaaaaugga aguccagccu uaccaacuug ugaaccuugu 780
cugaagggag ccagggccug ccaauggaac caccuccagg agcugcaacu gcuguuguca 840
uuaauaccau ugugucuauu uuuugagaga gauaaacuuu ucaugguguu acauuuugga 900
aaaaaaaaaa aaagacuagg ugaacaguca gguaggaaag cagcauaaca gucccuuaaa 960
uucugaucau guaggacauu cuucuuugcc cugggccugg gaaaaugcag cauguuccag 1020
agcaaaaguc cuaaugaggg gaacuaaacc agugggaccc aaaccaaugu ccuggcucac 1080
ugaggacccg uuagaaccaa aucucugggu guggacaggc ucccauacuu uucaaaaauu 1140
ccccugauga cuaaugaaca accagaggua agaaccagug gcccagagga auaaccagcc 1200
cagcuguugu acgagcucgc uaagcuggcu caggucaaug uugaauucuc ugcuaggcag 1260
cuccucauaa gaacuggcag agaugguucu uacacaacaa caggugacaa cuccagacuc 1320
ugccggaagu uccaggaucu ggguucccgg acaaugcaug acacucaguc cagcauugca 1380
gguggaagag cgacggugaa aagaccaaag ucaauuaaaa uguguuaacc aaaacaggaa 1440
acaugaguga ggugauugag aguguguuua acuuagaugu gugauuuuau caauacuuuc 1500
auuguucaaa aacucuuauu uuuuaaagau auuuucaaaa caaauccaaa cuuuacuuuu 1560
cauuccaaau ucguguuccg ucuauacuug cauuugggga aagauugaaa caaaacacaa 1620
auacuuugua gcaauguugg agugucaugu ucuuugcaga gggacaggaa aaaaaaagga 1680
uuuuuuuuuc uuaucaagag auacuguuuc cucaaggaga aagggcauca guccaaggca 1740
cugguuugcu caaaaagauu aguaaagaac aagcauauuu ugucuguggu gacaacauga 1800
ucuccccccc cccacuagua aacucacagc aucaguacgc aggcagugug augcauuuuc 1860
aaaguuccuc acuuuuccag auccaacagg acucuugugc acauacucgg uguuuccaug 1920
gcaaauccac uguguaugaa aauuagaccc uuccaaaaaa caaauuuacu agucaguaac 1980
caucaucagc acuuuuuuuc uguaccauga aauuugggaa caaaauuaaa gggcucuuga 2040
uugaaa 2046
<210> SEQ ID NO.11
<211> 1437
<212> RNA
<213> 人
<400> SEQ ID NO.11
acaaguauga agagaauguc gggagaggaa gugguggcua ugagucagca ugagucaucu 60
cguuccaaug agaaugaagg cugaggugug cgccuuuuuu uuuuuuccuu cuuagucgug 120
uguacaucau ugggaaugga gggaaauaaa ugacuggaug gucgcugcuu uuuaaguuuc 180
aaauugacau uccagacaag cggugccuga gcccgugccu gucuucagau cuucacagca 240
caguuccugg gaagguggag ccaccagccu cucccuggcu cugccgacuu ccaguucugg 300
aacaagaugg uuaaacucau uuuucccugc ucugcuccuc uaaauacaac uaaguaccuu 360
ggaaacuauu cagcagacaa ugauaaaggg cucugaaagc uagaagaaaa gguguacuug 420
caagaaaccu caggacuuga guaacagcaa cauggcaggc cagaaagcag acccagggag 480
gauagcacau gucuucggcu acacugguga aggcaucgug ccugcuccac agcacauuuu 540
uauucaagga aaggagaaag agacuaccua cugcauuucu gucacucgcu gaaaaggaca 600
cucugucaga aaaucuucua gcaaacuuca aagggcaaaa ucaccccuug uuacugauaa 660
agcccagaga gcuucagcag cuaacauucc cuggacaggg cacagcaagg auuugaaccu 720
aggucagucu ggccagaaca cccacaagcu uuccuuaacu cagugugcua ucuccccacg 780
acuaggucac uacugcuuua uaaucaccuu uguagccacc aguggauuuu gcucaucagu 840
auuuuucagg caauugauac uuuagauauu cagcugcaag acguaugcag uuuucauuga 900
caucuuuugg agaaacugac aaaccuggac uugacuuaau gccuuuggaa ccuuccaaga 960
uguuauauaa cucuagauag aaggcugggc cuccaugaug ucaggaaugu ugcauucuua 1020
uuuccccaua gauaaaccca uuuguccaca aagucaagga gucaggcaga ggcccuugcc 1080
auggggcuuu uuaggauaaa gcaacaagcc uggacuuugc ucuacaacag gguuuugcau 1140
agggaguggu augaccagau cccucaagaa agaaagcuua gagaccaggc cagaguccac 1200
ugcaguagcc cagucaagag aggaugguga cuuggacuug uaguagagcc aguuagaaug 1260
aaagaaauug acacauucag aaaugguuuu agagauagag ucaaacugga ccugauaaag 1320
aacuagagaa gcggagugag gauaaagaga agagccauga cugacucgga agauuuuguc 1380
uugaaaaacu ugagaacuca agacagagug aaauaaaauc acauguggga aaaaucu 1437
<210> SEQ ID NO.12
<211> 3470
<212> RNA
<213> 人
<400> SEQ ID NO.12
acaaguauga agagaauguc gggagaggaa gugguggcua ugagucagca ugagucaucu 60
cguuccaaug agaaugaagg cugaggugug cgccuuuuuu uuuuuuccuu cuuagucgug 120
uguacaucau ugggaaugga gggaaauaaa ugacuggaug gucgcugcuu uuuaaguuuc 180
aaauugacau uccagacaag cggugccuga gcccgugccu gucuucagau cuucacagca 240
caguuccugg gaagguggag ccaccagccu cucccugaca agcaaagugg aucagcaaag 300
gcugcaguca ccagcaucuu uuccaaccuu aaugaacugu auccucaaaa gaacacuauc 360
agacugguaa gacaagcauu auugucccac uucacagaug aagagcuugg gggcccugug 420
gauguguagg agagucggcc uuccuuuuua uaggccuuuu gcugagcuca gaggacagag 480
cagaagacaa agccgaaugc agcccuaagc agacacuauc ccagcccaag gagcuaugca 540
gacagcuccu gccuagagga gaaacaauuc ucuccuucag ccaggcaugu ggcacagagg 600
ugaacaggaa augcuuaggg agacaguuca cagauauaua uguacuucac agggcacaau 660
uuaauccaua aaucaaucau ggaucaccgc uaaagaaaac aaaauaugcu gccacuaauu 720
ugccaccacc cugugagcau gauuggauga uguuuauuuu gauuaggaga uugcuccauu 780
uauaaaucuu caauacaucc ugucccccua aaacggcauc ugggucuuuu gaggguuaaa 840
aaaaaaaaaa agugaaauug gaugagggau gagagcugga cuucugugug ucccgggguc 900
ccuggaucca cagccuggug ccuagcauca guuaagccca cgcugggguc gcaucacauc 960
ccgcaaagcc acgugcucug ugaggccaac aggagccccg ccggguggac cagcuggaau 1020
cucagagagc gccgacucug aaacuacccg gcucugcaga agcacgcugg gcccaggggc 1080
uucuagacug acagcuccau uuaucaacua ccuauugguu uuaaaaauug gagugucuuu 1140
uccgcguuga cugauuuugg cucuaagaga ugucgcuggu cauuucagag ugacugaacc 1200
uccccucuaa cagaucccgg gaauuguuuu caggaaaggu aaaaggcagc cuuuucuguc 1260
acaacacaac gcugagccgg cagccuggcu cugucaggau cuggggcucc cgcgcccgag 1320
aagcccagcc ucgccggcgg ccaaguucac cgcgaggccc cgcgcugccu gcgcugcgcu 1380
cccggacccg caccgaccgc agcgcgcgcc gccggugcuu cucccacccc agccuggaag 1440
cugccucccu ccgccuaugc cugcaggaua agaagcccga ggaggcggag cauggaacuc 1500
gacaguuaaa acauuuaaga gagaaaaccu agugucuugc uggccugaaa ucgaguacgc 1560
agcccggggu gaucaggguc ucccggcccg gaugugugag acuugcuucc ccugggcaau 1620
aggcgauacg augcuuuagg aggaaggugu cucucccucc uaagccccgg aggggagaac 1680
uuccaaagac agaaaaccac aggcuuccug gcacagagcu uucccuuuau cagcuaaagc 1740
agaaucuuuu cuggccuuaa ccuggccccu uccucuaacu gcaggcagag aggcagacag 1800
aaaagcacuu gcugaaacac aaaguuuugu ucuguccuca acgaacuguc uagagcugau 1860
ugcugauagu cguggugcau uaugccuucc ugguuuucau uuaauugggc accacgcugc 1920
cuuucaagac gccuuaaagg aaccaacaac caaauccaag agagcuggac agaccauuga 1980
acacacagua ggcugugucu cguggcuuuc guugucuggu gccucaaaga aaacaccaga 2040
aagauuguuu cuaagcuaga gccaccccag auugcuuaaa gugcaaagcu cacugcuguu 2100
ggggguaccc uugugagaca cuggaaagcu gguuuuaccg uggcccuaug aagaggaaga 2160
cugaaauuua gacaguaaua ccuuuacuag gauuggaaaa gauuugguua augacagccc 2220
ugucauuucu aaaacccauu aucacuguau gagagauucc uuugcgcugc auccucgaca 2280
gugcuuccua aggcucugcc gacuuccagu ucuggaacaa gaugguuaaa cucauuuuuc 2340
ccugcucugc uccucuaaau acaacuaagu accuuggaaa cuauucagca gacaaugaua 2400
aagggcucug aaagcuagaa gaaaaggugu acuugcaaga aaccucagga cuugaguaac 2460
agcaacaugu cuuggacgag ccugaggaug ucuacaagug gaagaaaaga agccacugga 2520
gcagaaggug gggaggauaa aauuuggagc aagauucuca aggaagcaac aagauccuaa 2580
ggaaaggaga aagagacuac cuacugcauu ucugucacuc gcugaaaagg acacucuguc 2640
agaaaaucuu cuagcaaacu ucaaagggca aaaucacccc uuguuacuga uaaagcccag 2700
agagcuucag cagcuaacau ucccuggaca gggcacagca aggauuugaa ccuaggucag 2760
ucuggccaga acacccacaa gcuuuccuua acucagugug cuaucucccc acgacuaggu 2820
cacuacugcu uuauaaucac cuuuguagcc accaguggau uuugcucauc aguauuuuuc 2880
aggcaauuga uacuuuagau auucagcugc aagacguaug caguuuucau ugacaucuuu 2940
uggagaaacu gacaaaccug gacuugacuu aaugccuuug gaaccuucca agauguuaua 3000
uaacucuaga uagaaggcug ggccuccaug augucaggaa uguugcauuc uuauuucccc 3060
auagauaaac ccauuugucc acaaagucaa ggagucaggc agaggcccuu gccauggggc 3120
uuuuuaggau aaagcaacaa gccuggacuu ugcucuacaa caggguuuug cauagggagu 3180
gguaugacca gaucccucaa gaaagaaagc uuagagacca ggccagaguc cacugcagua 3240
gcccagucaa gagaggaugg ugacuuggac uuguaguaga gccaguuaga augaaagaaa 3300
uugacacauu cagaaauggu uuuagagaua gagucaaacu ggaccugaua aagaacuaga 3360
gaagcggagu gaggauaaag agaagagcca ugacugacuc ggaagauuuu gucuugaaaa 3420
acuugagaac ucaagacaga gugaaauaaa aucacaugug ggaaaaaucu 3470
Claims (8)
1.一组胃癌RNA标志物，其特征在于，所述RNA分子选自:1)序列表中所示的RNA分子及其组合，AK001058序列如SEQ ID NO.1所示；INHBA-AS1(NR_027118)序列如SEQ ID NO.2所示，MIR4435-2HG(NR_015395)序列如SEQ ID NO.3所示，CEBPA-AS1(NR_026887)序列如SEQID NO.4所示；2)序列表中所示与SEQ ID NO.2核酸序列具有同源性的INHBA-AS1(NR_027119)序列 SEQ ID NO.5，与SEQ ID NO.3核酸序列具有同源性的MIR4435-2HG(NR_024373)序列SEQ ID NO.6、MIR4435-2HG(NR_136161)序列SEQ ID NO.7、MIR4435-2HG(NR_136162)序列SEQ ID NO.8、MIR4435-2HG(NR_136163)序列SEQ ID NO.9、MIR4435-2HG(NR_136164)序列SEQ ID NO.10、MIR4435-2HG(NR_136165)序列SEQ ID NO.11、MIR4435-2HG(NR_136166)序列SEQ ID NO.12所示。
2.根据权利要求1所述的RNA分子作为肿瘤标志物的应用，其特征在于，所述肿瘤为胃癌。
3.一种在分离的样本中检测权利要求1所述的RNA分子的方法，其包括测定离体样品中一种或多种RNA标志物的含量，其中所述一种或多种RNA标志物包括一种或多种选自序列表中的RNA标志物。
4.根据权利要求3所述的检测RNA分子的方法，其特征在于，所述方法为反转录实时定量PCR法。
5.一组寡核苷酸引物，其特征在于，该引物能够用来扩增权利要求1所述的RNA分子。
6.一种诊断胃癌的检测RNA分子的反转录PCR系统，其特征在于，该检测RNA分子系统包含权利要求5所述的寡核苷酸引物。
7.根据权利要求6的检测RNA分子的反转录PCR系统，其特征在于，该方法测定离体样本中权利1所述的RNA分子的水平；并比较被测定样本中权利要求1所述的RNA分子的水平与对照样本中的权利要求1所述的RNA分子的水平，与对照样本相比，被测定样本中该RNA分子的水平有显著改变，显示肿瘤的存在。
8.根据权利要求3-7任一项所述的检测RNA分子的方法，其特征在于，所述样本包括尿液、血液、血液衍生物或组织样本。
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106987651A (zh) * | 2017-06-07 | 2017-07-28 | 中南大学湘雅二医院 | 青光眼诊断分子标记物lncRNAsNR_026887、试剂盒及应用 |
| CN107177669A (zh) * | 2017-05-27 | 2017-09-19 | 叶国良 | 一种胃癌分子标志物hsa_circ_0006633及其应用 |
| EP3636771A4 (en) * | 2017-06-07 | 2021-05-19 | The Second Xiangya Hospital Of Central South University | THREE MOLECULAR MARKERS FOR DIAGNOSING A GLUCOMA, KIT AND APPLICATION |
| CN113262304A (zh) * | 2021-04-26 | 2021-08-17 | 暨南大学 | miR-4435-2HG和/或GDAP1基因抑制剂在制备治疗AML药物中的应用 |
| CN114292920A (zh) * | 2021-12-10 | 2022-04-08 | 中国人民解放军军事科学院军事医学研究院 | 一组胃癌前病变及胃癌早期诊断血浆rna标志物组合及应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105018638A (zh) * | 2015-08-25 | 2015-11-04 | 王振宁 | 胃癌发生相关分子标志物lncRNA HOTTIP的检测及应用 |
-
2016
- 2016-09-23 CN CN201610844907.5A patent/CN106148348B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105018638A (zh) * | 2015-08-25 | 2015-11-04 | 王振宁 | 胃癌发生相关分子标志物lncRNA HOTTIP的检测及应用 |
Non-Patent Citations (14)
| Title |
|---|
| HIROTA T等: "Accession: NR_136162.1", 《GENBANK》 * |
| HIROTA T等: "Accession: NR_136163.1", 《GENBANK》 * |
| HIROTA T等: "Accession: NR_136164.1", 《GENBANK》 * |
| HIROTA T等: "Accession: NR_136165.1", 《GENBANK》 * |
| HIROTA T等: "Accession: NR_136166.1", 《GENBANK》 * |
| HIROTA T等: "Accession:NR_136161.1", 《GENBANK》 * |
| OTA T等: "Accession: AK001058.1", 《GENBANK》 * |
| OTA T等: "Accession: NR_026887.1", 《GENBANK》 * |
| QUAN WANG等: "Upregulated INHBA expression is associated with poor survival in gastric cancer", 《MED ONCOL》 * |
| YANG Q等: "Accession:NR_015395.1", 《GENBANK》 * |
| YANG Q等: "Accession:NR_024373.1", 《GENBANK》 * |
| ZENG Z等: "Accession: NR_027119.1", 《GENBANK》 * |
| ZENG Z等: "Accession:NR_027118.1", 《GENBANK》 * |
| 石远凯等: "《国肿瘤内科进展 中国肿瘤医师教育》", 30 June 2015 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107177669A (zh) * | 2017-05-27 | 2017-09-19 | 叶国良 | 一种胃癌分子标志物hsa_circ_0006633及其应用 |
| CN107177669B (zh) * | 2017-05-27 | 2020-11-06 | 叶国良 | 一种胃癌分子标志物hsa_circ_0006633及其应用 |
| CN106987651A (zh) * | 2017-06-07 | 2017-07-28 | 中南大学湘雅二医院 | 青光眼诊断分子标记物lncRNAsNR_026887、试剂盒及应用 |
| EP3636771A4 (en) * | 2017-06-07 | 2021-05-19 | The Second Xiangya Hospital Of Central South University | THREE MOLECULAR MARKERS FOR DIAGNOSING A GLUCOMA, KIT AND APPLICATION |
| CN113262304A (zh) * | 2021-04-26 | 2021-08-17 | 暨南大学 | miR-4435-2HG和/或GDAP1基因抑制剂在制备治疗AML药物中的应用 |
| CN113262304B (zh) * | 2021-04-26 | 2022-12-06 | 暨南大学 | miR-4435-2HG和/或GDAP1基因抑制剂在制备治疗AML药物中的应用 |
| CN114292920A (zh) * | 2021-12-10 | 2022-04-08 | 中国人民解放军军事科学院军事医学研究院 | 一组胃癌前病变及胃癌早期诊断血浆rna标志物组合及应用 |
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