CN114561470B - 三阴性乳腺癌分子标志物及其应用 - Google Patents
三阴性乳腺癌分子标志物及其应用 Download PDFInfo
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Abstract
本发明涉及生物技术领域，具体涉及三阴性乳腺癌分子标志物及其应用。所述分子标志物包括以下任一种或其组合：1)RBCK1基因，其具有SEQ ID NO.1所示的DNA序列；2)RBCK1基因的表达产物。本发明的数据揭示了在体外和体内，RBCK1基因过度表达抑制TNBC细胞的进展，而RBCK1基因缺失促进TNBC细胞的进展，为TNBC治疗提供了一个有希望的治疗靶点。
Description
技术领域
本发明涉及生物技术领域，具体涉及三阴性乳腺癌分子标志物及其应用。
背景技术
乳腺癌是女性恶性肿瘤的主要病因，在女性癌症死亡率中排名第二。在所有乳腺恶性肿瘤亚型中，三阴性乳腺癌(TNBC)是最具侵袭性的亚型，预后最差。由于缺乏有效的靶点，如雌激素受体和人表皮生长因子受体2(可被三苯氧胺和赫赛汀阻断)，TNBC的治疗依赖于化疗。此外，TNBC的定义是一个专有概念，包括非ER和非HER2表达类型。因此，它包括这些类型的未分类乳腺癌，这使得识别某些分子标记物用于TBNC的靶向治疗成为一大挑战。最近的基因组研究表明，TNBC包括更高的基因组异常，如基因突变和基因扩增。一些癌基因，如YAP，在TNBC中被扩增。鉴于TNBC的高度异质性，寻找新的乳腺癌治疗靶点是迫切而必要的。
发明内容
针对现有技术存在的问题，本发明提供了三阴性乳腺癌分子标志物及其应用。
本发明的第一个方面，提供三阴性乳腺癌分子标志物，所述分子标志物包括以下任一种或其组合：
1)RBCK1基因，其具有SEQ ID NO.1所示的DNA序列；
2)RBCK1基因的表达产物。
进一步的，所述RBCK1基因的表达产物包括RBCK1 mRNA和/或RBCK1蛋白。
更进一步的，所述RBCK1蛋白具有SEQ ID NO.2所示的氨基酸序列。
本发明的第二个方面，提供所述三阴性乳腺癌分子标志物的检测试剂在制备三阴性乳腺癌诊断和/或预后的工具中应用。
进一步的，所述检测试剂包括特异扩增RBCK1基因的引物，所述特异扩增RBCK1基因的引物序列如SEQ ID NO.3和SEQ ID NO.4所示。
进一步的，所述检测试剂包括RBCK1蛋白的免疫检测产品，所述特异扩增RBCK1基因的引物序列如SEQ ID NO.9和SEQ ID NO.10所示。
本发明的第三个方面，提供一种筛选治疗三阴性乳腺癌的候选药物的方法，所述方法包括：
用待测物质处理表达或含有所述三阴性乳腺癌分子标志物的体系；和
检测体系中所述三阴性乳腺癌分子标志物的表达水平；
其中，若所述待筛选物质可以升高所述三阴性乳腺癌分子标志物的表达水平，则表明该待筛选物质是治疗三阴性乳腺癌的候选药物。
本发明的第四个方面，提供所述三阴性乳腺癌分子标志物的表达促进剂在制备治疗三阴性乳腺癌的药物中的应用。
进一步的，所述表达促进剂包括含有RBCK1基因的过表达载体。
本发明具有如下有益效果：
RBCK1首次被鉴定为线性泛素组装复合物(LUBAC)的重要组成部分，在免疫应答中促进NFKB信号传导。进一步的研究表明，RBCK1还通过反式激活雌激素受体α促进了管腔型乳腺癌的生长和内分泌抵抗。但是本发明的数据揭示了RBCK1基因在TNBC进展中的相反作用。在体外和体内，RBCK1基因过度表达抑制TNBC细胞的进展，而RBCK1基因缺失促进TNBC细胞的进展。本发明揭示了RBCK1基因在不同亚型乳腺癌患者中的多面功能，为TNBC治疗提供了一个有希望的治疗靶点。
附图说明
图1为RBCK1 siRNA或siControl转染MDA-MB-231细胞48小时后，通过QPCR和Westernblot测RBCK1 mRNA水平(A)和RBCK1蛋白(B)。
图2为CCK-8分析测定转染RBCK1 siRNA或siControl后特定时间点MDA-MB-231(A)和BT549细胞(B)的代谢活性。
图3为Transwell小室模型实验检测转染RBCK1 siRNA或siControl后TNBC细胞的迁移和侵袭能力，图A为MDA-MB-231的迁移细胞数，图B为BT549的迁移细胞数，图C为MDA-MB-231的侵袭细胞数，图D为BT549的侵袭细胞数。
图4为伤口愈合实验检测转染RBCK1 siRNA或siControl后TNBC细胞的伤口闭合度，图A为MDA-MB-231细胞，图B为BT549细胞。
图5为FACS分析转染RBCK1 siRNA或siControl后TNBC细胞的凋亡比例，图A为MDA-MB-231细胞，图B为BT549细胞。
图6为FACS分析转染RBCK1 siRNA或siControl后TNBC细胞CD24-CD44+的比例，图A为MDA-MB-231细胞，图B为BT549细胞。
图7为Western blot检测Flag-RBCK1在HEK-293细胞中的蛋白水平，β-肌动蛋白被用作内参照物。
图8为过表达RBCK1的MDA-MB-231(A)和BT549细胞(B)的代谢活性。
图9为Transwell小室模型实验检测过表达RBCK1的TNBC细胞的迁移和侵袭能力，图A为MDA-MB-231的迁移细胞数，图B为BT549的迁移细胞数，图C为MDA-MB-231的侵袭细胞数，图D为BT549的侵袭细胞数。
图10为伤口愈合实验检测过表达RBCK1的TNBC细胞的伤口闭合度，图A为MDA-MB-231细胞，图B为BT549细胞。
图11为FACS分析过表达RBCK1的TNBC细胞的凋亡比例，图A为MDA-MB-231细胞，图B为BT549细胞。
图12为FACS分析过表达RBCK1的TNBC细胞中CD24-CD44+的比例，图A为MDA-MB-231细胞，图B为BT549细胞。
图13为异种移植模型中，不同处理小鼠的肿瘤生长照片(A)、曲线(B)和重量(C)。
具体实施方式
下面结合附图和具体实施例对本发明进行详细说明，但不应理解为本发明的限制。如未特殊说明，下述实施例中所用的技术手段为本领域技术人员所熟知的常规手段，下述实施例中所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
本发明中所涉及的RBCK1基因的编码序列具有SEQ ID NO.1所示的DNA序列，其中，该序列后三个碱基不翻译氨基酸；RBCK1蛋白的氨基酸序列为SEQ ID NO.2所示的序列。
MDA-MB-231、BT549和HEK293细胞来自美国类型培养收集中心(ATCC)。MDA-MB-231和HEK293细胞在Dulbecco改良的Eagle培养基中培养，该培养基含有4.5g/L葡萄糖和4mML-谷氨酰胺(DMEM，41965，Life Technologies)，并补充10％胎牛血清(FBS，10270，LifeTechnologies)。BT549细胞在RPMI-1640培养基(42401，Life Technologies)中培养，并添加2mM L-谷氨酰胺(25030，Life Technologies)和10％FBS。所有细胞系均经细胞系鉴定。在PowerPlex 21系统中，通过短串联重复序列(STR)分析进行细胞系验证。我们发现MDA-MB-231、BT549和HEK293细胞系的STR数据与ATCC中的STR数据一致。
实施例1：RBCK1缺失促进TNBCA-B中的癌细胞进展
1、细胞转染
将105个MDA-MB-231和BT549细胞接种到24孔板中，并用50μM RBCK1siRNA或siControl转染进行转染，siRNA序列信息见表1：
表1siRNA序列信息
注：siRNA#1的正义链和反义链，si RBCK1#2的正义链和反义链的3'端均修饰有dTdT悬垂。
2、RNA分离和定量实时PCR(qRT-PCR)
使用RNeasy plus微型试剂盒(天根)根据说明书提取总RNA。使用RevertAidFirst Strand cDNA Synthesis Kit(Thermo，立陶宛)进行反转录。qRT-PCR是在7500FastReal-Time PCR System(Applied Biosystems,Singapore)中使用qPCR MasterMix(Promega,USA)。36B4基因被用作内部对照。引物序列为见表2：
表2qRT-PCR引物序列信息
所有引物对的特异性均通过熔融曲线分析进行检查。
3、Westernblot分析
标准Westernblot程序用于检测细胞在Westernblot分析中，使用以下抗体分析蛋白质表达：抗肌动蛋白(3700，Cell Signaling Technology，1:1000)，抗RBCK1(26367-1-AP，Proteintech，1:1000)。蛋白质信号通过ECL试剂盒(美国马萨诸塞州比利卡Millipore公司)检测。
4、细胞活力的量化
siRBCK1或siControl在24孔板中转染MDA-MB-231和BT549细胞。转染24小时后，对细胞进行计数，并将4000个细胞接种到96孔板中。我们测量特定时间点的相对细胞活力。通过测量450nm处的吸光度，使用CCK8细胞增殖试剂测定细胞数量。
5、Trans-well分析
我们使用了一种新的二室板来检查细胞迁移和侵袭的能力。为了进行迁移试验，将无血清培养基中的细胞接种到上腔。对于侵入试验，12小时后，在上腔涂上Matrigel膜(BD Biocat，USA)，我们小心地取出细胞，固定侵入细胞膜的细胞，并填充结晶紫染色溶液。然后在显微镜下观察细胞并拍照，并用ImageJ计数。
6、创伤愈合试验。
将细胞接种到含有1％FBS的12孔培养皿中。当细胞100％融合时，我们用黄色移液管的尖端划伤它。在指定时间点检测伤口间隙，并用最早时间点进行标准化。伤口愈合率计算公式：[1-(给定时间的伤口宽度/t＝0时的伤口宽度)]×100％。
7、流式细胞术分析
用siRBCK1或siControl转染MDA-MB-231和BT549细胞。转染24小时后，用碘化丙啶和膜联蛋白V(PI/Annexin V)对细胞进行染色。用BD-LSR流式细胞仪测定荧光强度。对于(CD44/CD24)细胞比率分析，用siRBCK1或siControl转染MDA-MB-231和BT549细胞。转染24小时后，对数生长期的乳腺癌细胞用0.25％胰蛋白酶消化，PBS洗涤3次，然后在100ul PBS中再悬浮，然后用抗CD44-PE和抗CD24-FITC染色。然后用PBS洗涤样品3次，最后在200μL的条件下重新在PBS中停留。在BDAccuriTM C6流式细胞仪(BD Bioscience)上进行流式细胞术分析。根据流式细胞术中CD44和CD24阳性亚群的百分比，计算CD44和CD24(CD44/CD24)在不同亚型乳腺癌细胞系中的表达率。
结果：我们首先检测了RBCK1在TNBC细胞中的沉默效率，其中QPCR和Westernblot数据显示，RBCK1在MDA-MB-231细胞中可以显著缺失(图1)。CCK8分析表明，RBCK1缺失对MDA-MB-231细胞和BT549细胞的增殖速度没有影响(图2)。在渗透滤膜和基底膜的跨孔检测中，RBCK1缺失可促进TNBC细胞的侵袭和迁移(图3)。伤口愈合实验证实了类似的结果，即在MDA-MB-231和BT549细胞模型中，RBCK1缺陷细胞比野生型细胞具有更快的伤口愈合速度(图4)。此外，通过PI/AnnexinV双重染色结合FACS分析，由于RBCK1缺乏，MDA-MB-231和BT549细胞中凋亡细胞的比例可能会降低(图5)。因为一些研究表明TNBC(CD44+/CD24-)的干性也是癌症进展的一个重要属性。我们研究了RBCK1缺失对TNBC干细胞的影响，其中数据显示RBCK1缺失可进一步增强MDA-MB-231和BT549细胞的干细胞特性(图6)。
实施例2：RBCK1过表达在体外和体内抑制TNBC细胞的进展
1、细胞转染
从Origene(RC229128)获得Flag-RBCK1质粒。质粒用Lipofectamine 2000(1662298，Invitrogen)转染。将105个HEK-293、MDA-MB-231和BT549细胞分别接种到24孔板中，并用0.5μg Flag-RBCK1或Flag载体转染，培养特定的时间后，进行转染后的其它检测步骤。
2、Westernblot分析
标准Westernblot程序用于检测细胞在Westernblot分析中，使用以下抗体分析蛋白质表达：抗Flag(Ab49763，Abcam，1:1000)，抗肌动蛋白(3700，Cell SignalingTechnology，1:1000)，蛋白质信号通过ECL试剂盒(美国马萨诸塞州比利卡Millipore公司)检测。
3、细胞活力的量化
Flag-RBCK1或Flag载体在24孔板中转染MDA-MB-231和BT549细胞，转染后的不同时间对细胞进行计数，并将4000个细胞接种到96孔板中。我们测量特定时间点的相对细胞活力。通过测量450nm处的吸光度，使用CCK8细胞增殖试剂测定细胞数量。
4、Trans-well分析
我们使用了一种新的二室板来检查转染Flag-RBCK1或Flag载体的MDA-MB-231和BT549细胞迁移和侵袭的能力。为了进行迁移试验，将无血清培养基中的细胞接种到上腔。对于侵入试验，12小时后，在上腔涂上Matrigel膜(BD Biocat，USA)，我们小心地取出细胞，固定侵入细胞膜的细胞，并填充结晶紫染色溶液。然后在显微镜下观察细胞并拍照，并用ImageJ计数。
5、创伤愈合试验
将细胞接种到含有1％FBS的12孔培养皿中。当细胞100％融合时，我们用黄色移液管的尖端划伤它。在指定时间点检测伤口间隙，并用最早时间点进行标准化。伤口愈合率计算公式：[1-(给定时间的伤口宽度/t＝0时的伤口宽度)]×100％。
6、流式细胞术分析
MDA-MB-231细胞转染Flag-RBCK1或Flag载体24小时后，用碘化丙啶和膜联蛋白V(PI/AnnexinV)对细胞进行染色。用BD-LSR流式细胞仪测定荧光强度。对于(CD44/CD24)细胞比率分析，用siRBCK1或siControl转染MDA-MB-231和BT549细胞。转染24小时后，对数生长期的乳腺癌细胞用0.25％胰蛋白酶消化，PBS洗涤3次，然后在100ul PBS中再悬浮，然后用抗CD44-PE和抗CD24-FITC染色。然后用PBS洗涤样品3次，最后在200μL的条件下重新在PBS中停留。在BDAccuriTM C6流式细胞仪(BD Bioscience)上进行流式细胞术分析。根据流式细胞术中CD44和CD24阳性亚群的百分比，计算CD44和CD24(CD44/CD24)在不同亚型乳腺癌细胞系中的表达率。
7、体内致瘤实验
在体内致瘤实验中，每组均使用5周龄的雌性BALB/c裸鼠。实验组每只小鼠皮下注射3×106个转染Flag-RBCK1的MDA-MB-231细胞，对照组每只小鼠皮下注射3×106个转染Flag载体的MDA-MB-231细胞。每隔3-4天测量一次MDA-MB-231肿瘤异种移植物，肿瘤体积按长×宽2/2计算。肿瘤细胞注射后6周处死小鼠。
结果：为了证实表型，我们通过慢病毒感染系统在TNBC细胞中过表达RBCK1。图7证实了RBCK1的外源性表达。CCK8分析表明，RBCK1表达增加可导致MDA-MB-231和BT549细胞增殖受到抑制(图8)。在Transwell小室模型实验中，RBCK1的过度表达可降低TNBC细胞的侵袭和迁移(图9)。伤口愈合实验证实了类似的结果，即在MDA-MB-231和BT549细胞模型中，RBCK1过表达细胞降低了伤口闭合速度(图10)。PI/AnnexinV双重染色结合FACS分析表明，RBCK1过度表达可促进MDA-MB-231和BT549细胞的凋亡(图11)。我们还通过CD44和CD24标记物测量了细胞的干细胞特性，其中RBCK1过度表达可降低CD44+/CD24-细胞的比例(图12)。然后，我们在MDA-MB-231细胞中建立了稳定的RBCK1过度表达模型，并进一步建立了异种移植小鼠模型来研究RBCK1在体内的作用。数据证实，RBCK1的过度表达可降低体内肿瘤的生长速率(图13)。
尽管已描述了本发明的优选实施例，但本领域内的技术人员一旦得知了基本创造性概念，则可对这些实施例作出另外的变更和修改。所以，所附权利要求意欲解释为包括优选实施例以及落入本发明范围的所有变更和修改。
显然，本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样，倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内，则本发明也意图包含这些改动和变型在内。
序列表
<110> 新乡医学院
<120> 三阴性乳腺癌分子标志物及其应用
<141> 2022-03-19
<160> 16
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1023
<212> DNA
<213> 人源
<400> 1
atggggtgcg gcagaatggg gacagtgcct acctctatct gctgtcagcc cgcaacacct 60
ccctcaaccc tcaggagctg cagcgggagc ggcagctgcg gatgctggaa gatctgggct 120
tcaaggacct cacgctgcag ccgcggggcc ctctggagcc aggcccccca aagcccgggg 180
tcccccagga acccggacgg gggcagccag atgcagtgcc tgagccccca ccggtgggct 240
ggcagtgccc cgggtgcacc ttcatcaaca agcccacgcg gcctggctgt gagatgtgct 300
gccgggcgcg ccccgaggcc taccaggtcc ccgcctcata ccagcccgac gaggaggagc 360
gagcgcgcct ggcgggcgag gaggaggcgc tgcgtcagta ccagcaggga gtgcctgcag 420
ggcaccatcc gcaacagcca ggaggcggag gtctcctgcc ccttcattga caacacctac 480
tcgtgctcgg gcaagctgct ggagagggag atcaaggcgc tcctgacccc tgaggattac 540
cagcgatttc tagacctggg catctccatt gctgaaaacc gcagtgcctt cagctaccat 600
tgcaagaccc cagattgcaa gggatggtgc ttctttgagg atgatgtcaa tgagttcacc 660
tgccctgtgt gtttccacgt caactgcctg ctctgcaagg ccatccatga gcagatgaac 720
tgcaaggagt atcaggagga cctggccctg cgggctcaga acgatgtggc tgcccggcag 780
acgacagaga tgctgaaggt gatgctgcag cagggcgagg ccatgcgctg cccccagtgc 840
cagatcgtgg tacagaagaa ggacggctgc gactggatcc gctgcaccgt ctgccacacc 900
gagatctgct gggtcaccaa gggcccacgc tggggccctg ggggcccagg agacaccagc 960
gggggctgcc gctgcagggt aaatgggatt ccttgccacc caagctgtca gaactgccac 1020
tga 1023
<210> 2
<211> 340
<212> PRT
<213> 人源
<400> 2
Met Gly Cys Gly Arg Met Gly Thr Val Pro Thr Ser Ile Cys Cys Gln
1 5 10 15
Pro Ala Thr Pro Pro Ser Thr Leu Arg Ser Cys Ser Gly Ser Gly Ser
20 25 30
Cys Gly Cys Trp Lys Ile Trp Ala Ser Arg Thr Ser Arg Cys Ser Arg
35 40 45
Gly Ala Leu Trp Ser Gln Ala Pro Gln Ser Pro Gly Ser Pro Arg Asn
50 55 60
Pro Asp Gly Gly Ser Gln Met Gln Cys Leu Ser Pro His Arg Trp Ala
65 70 75 80
Gly Ser Ala Pro Gly Ala Pro Ser Ser Thr Ser Pro Arg Gly Leu Ala
85 90 95
Val Arg Cys Ala Ala Gly Arg Ala Pro Arg Pro Thr Arg Ser Pro Pro
100 105 110
His Thr Ser Pro Thr Arg Arg Ser Glu Arg Ala Trp Arg Ala Arg Arg
115 120 125
Arg Arg Cys Val Ser Thr Ser Arg Glu Cys Leu Gln Gly Thr Ile Arg
130 135 140
Asn Ser Gln Glu Ala Glu Val Ser Cys Pro Phe Ile Asp Asn Thr Tyr
145 150 155 160
Ser Cys Ser Gly Lys Leu Leu Glu Arg Glu Ile Lys Ala Leu Leu Thr
165 170 175
Pro Glu Asp Tyr Gln Arg Phe Leu Asp Leu Gly Ile Ser Ile Ala Glu
180 185 190
Asn Arg Ser Ala Phe Ser Tyr His Cys Lys Thr Pro Asp Cys Lys Gly
195 200 205
Trp Cys Phe Phe Glu Asp Asp Val Asn Glu Phe Thr Cys Pro Val Cys
210 215 220
Phe His Val Asn Cys Leu Leu Cys Lys Ala Ile His Glu Gln Met Asn
225 230 235 240
Cys Lys Glu Tyr Gln Glu Asp Leu Ala Leu Arg Ala Gln Asn Asp Val
245 250 255
Ala Ala Arg Gln Thr Thr Glu Met Leu Lys Val Met Leu Gln Gln Gly
260 265 270
Glu Ala Met Arg Cys Pro Gln Cys Gln Ile Val Val Gln Lys Lys Asp
275 280 285
Gly Cys Asp Trp Ile Arg Cys Thr Val Cys His Thr Glu Ile Cys Trp
290 295 300
Val Thr Lys Gly Pro Arg Trp Gly Pro Gly Gly Pro Gly Asp Thr Ser
305 310 315 320
Gly Gly Cys Arg Cys Arg Val Asn Gly Ile Pro Cys His Pro Ser Cys
325 330 335
Gln Asn Cys His
340
<210> 3
<211> 19
<212> DNA/RNA
<213> 人工序列
<400> 3
gugccuaccu cuaucugcu 19
<210> 4
<211> 19
<212> DNA/RNA
<213> 人工序列
<400> 4
agcagauaga gguaggcac 19
<210> 5
<211> 19
<212> DNA/RNA
<213> 人工序列
<400> 5
gccuucagcu accauugca 19
<210> 6
<211> 19
<212> DNA/RNA
<213> 人工序列
<400> 6
ugcaauggua gcugaaggc 19
<210> 7
<211> 21
<212> DNA/RNA
<213> 人工序列
<400> 7
uucuccgaac gugucacgut t 21
<210> 8
<211> 21
<212> DNA/RNA
<213> 人工序列
<400> 8
acgugacacg uucggagaat t 21
<210> 9
<211> 19
<212> DNA
<213> 人工序列
<400> 9
tgctcagatg cacaccgtc 19
<210> 10
<211> 21
<212> DNA
<213> 人工序列
<400> 10
caagactggt gggaagccat a 21
<210> 11
<211> 20
<212> DNA
<213> 人工序列
<400> 11
ggcgacctgg aagtccaact 20
<210> 12
<211> 19
<212> DNA
<213> 人工序列
<400> 12
ccatcagcac cacagcctc 19
<210> 13
<211> 18
<212> DNA
<213> 人工序列
<400> 13
ctcgcggctt accgactg 18
<210> 14
<211> 20
<212> DNA
<213> 人工序列
<400> 14
ggctctgctt ctctagcctg 20
<210> 15
<211> 20
<212> DNA
<213> 人工序列
<400> 15
agcagcctga aaaagggcaa 20
<210> 16
<211> 20
<212> DNA
<213> 人工序列
<400> 16
agcctgtaga agggaaacgc 20
Claims (1)
1.RBCK1基因的过表达载体在制备治疗三阴性乳腺癌的药物中的应用，其特征在于，所述RBCK1基因的核苷酸序列如SEQ ID NO.1所示。
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1890381A (zh) * | 2003-09-24 | 2007-01-03 | 肿瘤疗法科学股份有限公司 | 诊断乳腺癌的方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1890381A (zh) * | 2003-09-24 | 2007-01-03 | 肿瘤疗法科学股份有限公司 | 诊断乳腺癌的方法 |
Non-Patent Citations (5)
| Title |
|---|
| Expression of the three components of linear ubiquitin assembly complex in breast cancer;Amirhossein Kharman-Biz 等;《PLoS ONE》;第13卷(第5期);第1 页摘 要、第3-4、 6-8 页 * |
| NM_001323958.2 Homo sapiens RANBP2-type and C3HC4-type zinc finger containing 1 (RBCK1), transcript variant 4, mRNA;Phadke R 等;《GenBank》;第4-5页 * |
| Phadke R 等.NM_001323958.2 Homo sapiens RANBP2-type and C3HC4-type zinc finger containing 1 (RBCK1), transcript variant 4, mRNA.《GenBank》.2022,第4-5页. * |
| RBCK1 Drives Breast Cancer Cell Proliferation by Promoting Transcription of Estrogen Receptor α and Cyclin B1;Nina Gustafsson 等;《Cancer Res》;第70卷(第3期);第1265 -1274页 * |
| 乳腺癌转移相关蛋白蛋白质组学初步研究;高永生 等;《山东大学学报(医学版)》;第47卷(第7期);第61-64、69页 * |
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