CN117402972A - m6A甲基转移酶IGF2BP2在制备用于诊断乳腺癌的新辅助放疗抵抗标记物中的应用 - Google Patents
m6A甲基转移酶IGF2BP2在制备用于诊断乳腺癌的新辅助放疗抵抗标记物中的应用 Download PDFInfo
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Abstract
本发明属于m6a甲基化转移酶科学技术领域,具体涉及m6A甲基转移酶IGF2BP2在制备用于诊断乳腺癌的新辅助放疗抵抗标记物中的应用,其中,所述诊断乳腺癌为采用RT‑qPCR技术检测乳腺癌组织样本中IGF2BP2基因的表达水平,所述IGF2BP2基因在乳腺癌组织样品中表达上调。本发明首次确认了IGF2BP2在乳腺癌新辅助放疗抵抗中的作用,IGF2BP2在乳腺癌放疗抵抗组织中表达量上调,并且促进了乳腺癌细胞放疗抵抗能力。本发明发现m6A甲基转移酶IGF2BP2可以用来预测乳腺癌放疗抵抗,帮助患者及时地调整治疗策略,可作为临床乳腺癌诊断和治疗的潜在靶点。
Description
技术领域
本发明属于m6a甲基化转移酶科学技术领域,具体涉及m6A甲基转移酶IGF2BP2在制备用于诊断乳腺癌的新辅助放疗抵抗标记物中的应用。
背景技术
乳腺癌已成为世界上最常见的恶性肿瘤之一,严重危害女性的健康和生命。在美国,每8位女性中将有一人会发生乳腺癌。虽然亚洲乳腺癌发病率较西方一直较低,但由于生活方式的西方化,不少大中城市乳腺癌发病率呈现比较明显的上升趋势,每年有高达3-4%的新增病例,已超过宫颈癌,发展为女性发病率最高的恶性肿瘤,且呈现年轻化趋势。近些年来,乳腺癌在治疗方法上的改进和发展使乳腺癌死亡率明显降低。临床治疗方案上,手术切除结合放化疗、内分泌治疗、靶向治疗等综合治疗是目前治疗乳腺癌的常规方法。放射治疗是乳腺癌综合治疗的一个重要手段,可以提高患者的生存质量及远期生存率,特别对于Ⅲ、Ⅳ期及保乳手术患者有重要价值。但由于个体之间或肿瘤细胞本身对射线的反应存在很大差异,即存在细胞内在放射敏感性(intrinsicradiosenstivity)差异,往往导致疗效不佳。此外,在放疗过程中发生的辐射耐受现象,已成为晚期乳腺癌患者放疗失败的一个重要原因。因此,降低肿瘤的辐射抗性,提高肿瘤的辐射敏感性,同时尽可能减轻或避免正常组织的辐射损伤,对于临床工作具有重要意义。
近年来,表观遗传修饰在恶性肿瘤发生发展中的调控作用备受关注。RNA表观遗传学是在RNA水平调控基因表达的重要途径。表观遗传学的可逆性为疾病的早期干预和治疗提供了科学依据。迄今为止,已鉴定出170多种RNA修饰,已知甲基化修饰是最常见的。研究发现,RNA甲基化修饰通常包括N1-甲基腺苷(m1A)、5-甲基胞嘧啶(m5C)、5-羟甲基胞嘧啶(5hmC)、N6-甲基腺苷(m6A)和7-甲基鸟嘌呤(m7G)。其中,m6A修饰是哺乳动物中最丰富和最重要的mRNA修饰,占甲基化核糖核苷酸总数的约50%。m6A甲基化几乎影响RNA代谢的每个方面,包括RNA表达,剪接,核输出,翻译,衰变和RNA-蛋白质相互作用。越来越多的研究表明,RNA中的m6A修饰在许多生理过程中起着至关重要的作用,包括昼夜节律,精子发生,胚胎发生,热休克反应,DNA损伤反应,多能性和重编程。新的证据表明m6ARNA甲基化在肿瘤的发生和发展中起重要作用,异常的m6A修饰与癌症密切相关。最新的研究显示m6A相关因子参与了肿瘤放疗过程。例如胶质母细胞瘤细胞中的辐射增强了METTL3表达,并通过募集hUR增加SOX2的稳定性诱导了放疗耐受。同样,METTL3的选择性敲低导致胰腺癌细胞系对放疗敏感。橡皮擦蛋白FTO通过β-catenin的去甲基化诱导宫颈鳞癌的化学放射抗性。综上所述,m6A可能参与了肿瘤的放射耐受,可能成为乳腺癌放疗增敏的潜在靶向策略,但具体的机制仍需要深入探索。
胰岛素样生长因子2-mRNA结合蛋白2(Insulin-likegrowthfactor2mRNA-bindingprotein2,IGF2BP2)是m6A甲基化修饰的重要甲基转移酶结合蛋白,且作为剪接调节因子发挥重要作用。IGF2BP2可以与IGF2mRNA及其他多个靶mRNA结合,稳定并介导其翻译IGF2BP2可以通过参与mRNA的m6A甲基化修饰、激活MAPK、PI3K/Akt信号通路等多种方式参与细胞分化、增殖及能量代谢。目前关于IGF2BP2是否参与乳腺癌新辅助放疗抵抗还未见报道。探寻IGF2BP2在乳腺癌新辅助放疗抵抗的作用具有重要意义,对乳腺癌新辅助放疗抵抗的改善起着重要作用,并且为乳腺癌的基因靶向治疗提供可能。
发明内容
本发明的目的在于提供m6A甲基转移酶IGF2BP2在制备用于诊断乳腺癌的新辅助放疗抵抗标记物中的应用,所述的这种应用能够解决现有技术无法预测乳腺癌放疗敏感性的技术问题。
本发明的目的是通过如下技术方案实现的:
本发明提供了一种m6A甲基转移酶IGF2BP2在制备用于诊断乳腺癌的新辅助放疗抵抗标记物中的应用。
进一步的,所述诊断乳腺癌为采用RT-qPCR技术检测乳腺癌组织样本中IGF2BP2基因的表达水平。
进一步的,所述IGF2BP2基因在乳腺癌组织样品中表达上调。
本发明还提供了一种用于诊断乳腺癌的新辅助放疗抵抗标记物在制备检测乳腺癌新辅助放疗抵抗的试剂盒、试纸或芯片中的应用,所述用于诊断乳腺癌的新辅助放疗抵抗标记物包括m6A甲基转移酶IGF2BP2。
所述试剂盒、试纸或芯片中,用于扩增m6A甲基转移酶IGF2BP2的基因的正向引物序列如SEQ ID NO.1所示;反向引物序列如SEQ ID NO.2所示。
本发明还提供了一种用于诊断乳腺癌的新辅助放疗抵抗标记物在制备治疗乳腺癌的药物和/或制备调控乳腺癌新辅助放疗抵抗的药物中的应用,所述用于诊断乳腺癌的新辅助放疗抵抗标记物包括m6A甲基转移酶IGF2BP2。
进一步的,所述的调控为通过如下任一种方式实现:
M1:促进m6A甲基转移酶IGF2BP2表达,以增加乳腺癌放疗抵抗;
M2:抑制m6A甲基转移酶IGF2BP2表达,以降低乳腺癌放疗抵抗。
进一步的,M1中所述的促进m6A甲基转移酶IGF2BP2表达为通过在细胞内过表达m6A甲基转移酶IGF2BP2的方法实现;方式M2中所述的抑制m6A甲基转移酶IGF2BP2表达为通过试剂或药物抑制m6A甲基转移酶IGF2BP2的方法实现。
进一步的,所述试剂或药物为核酸抑制剂、蛋白抑制剂或蛋白结合分子。
申请人利用前期收集的33例乳腺癌患者放疗前活检组织样本,参照术后病理AJCC版肿瘤退缩分级(TumorRegression Grade,TRG)将其分成两组,TRG=(0+1)为放疗敏感组,TRG=(2+3)为放疗抵抗组,分别检测IGF2BP2含量,结果显示:放疗抵抗组m6A甲基化修饰水平IGF2BP2显著高于放疗敏感组。
申请人进一步选取33例乳腺癌患者活检样本石蜡白片,分别检测IGF2BP2蛋白表达水平。结果显示:IGF2BP2在癌组织中高表达,且与乳腺癌放疗抵抗呈正相关,患者总生存时间缩短,提示预后不良。
申请人利用乳腺癌放疗抵抗细胞模型(MCF7-R),分别检测IGF2BP2的mRNA及蛋白表达水平。结果显示:IGF2BP2在放疗抵抗细胞中表达水平升高。
为进一步验证干预m6A甲基转移酶IGF2BP2的表达水平,可相应逆转乳腺癌细胞的放疗敏感性。申请人利用慢病毒感染筛选构建IGF2BP2干扰及过表达稳转株,给予4Gy辐照剂量处理后,结果显示:干扰IGF2BP2表达水平的放疗抵抗细胞株,增殖能力减弱、细胞凋亡增多、克隆形成减少;再将稳定干扰IGF2BP2表达水平的放疗抵抗细胞株接种至裸鼠皮下,构建辐照动物模型,结果显示:干扰表达IGF2BP2辐照组瘤体体积明显缩小,放疗敏感性增强。
可见,能够利用m6A甲基转移酶IGF2BP2制备用于诊断乳腺癌的新辅助放疗抵抗标记物,进一步的,申请人构建了一对可特异性扩增IGF2BP2基因的引物,所述引物序列如下:
IGF2BP2正向引物(SEQ ID NO.1):5’-AGCCCCACTTCCTACCAGATG-3’;
IGF2BP2反向引物(SEQ ID NO.2):5’-TGAGAACTGTTATTTCCCCATGC-3’。
通过上述引物能够实现制备一种诊断乳腺癌的产品,采用RT-qPCR技术检测乳腺癌组织样本中IGF2BP2基因的表达水平进而诊断乳腺癌;同时,利用上述机制还可制备一种治疗乳腺癌的药物和/或制备调控乳腺癌新辅助放疗抵抗的药物,其中调控是指促进或抑制IGF2BP2表达,以增加或降低乳腺癌放疗抵抗;IGF2BP2基因表达的抑制剂为核酸抑制剂、蛋白抑制剂或蛋白结合分子。
本发明和已有技术相比,其技术进步是显著的,本发明具有的有益效果:本发明首次确认了IGF2BP2在乳腺癌新辅助放疗抵抗中的作用,IGF2BP2在乳腺癌放疗抵抗组织中表达量上调,并且促进了乳腺癌细胞放疗抵抗能力。本发明发现m6A甲基转移酶IGF2BP2可以用来预测乳腺癌放疗抵抗,帮助患者及时地调整治疗策略,可作为临床乳腺癌诊断和治疗的潜在靶点。
附图说明
图1为本发明乳腺癌放疗抵抗组(TRG=2+3)IGF2BP2与放疗敏感组在mRNA水平上的比较图;
图2为本发明完全敏感组、部分敏感组、部分抵抗组以及完全抵抗组IGF2BP2在mRNA水平上的比较图;
图3为本发明甲基转移酶IGF2BP2在细胞中表达图,其中图3A为不同表达水平的染色对比图,图3B为不同表达水平的生存概率图;
图4为本发明放疗抵抗细胞模型与亲代细胞的差异图;
图5为本发明放疗抵抗细胞模型与亲代细胞的IGF2BP2表达水平图,其中图5A为mRNA表达水平,图5B为蛋白表达水平,图5C为灰度分析表达水平;
图6为本发明干扰表达IGF2BP2空白载体、干扰表达IGF2BP2、干扰表达IGF2BP2空白载体+6Gy辐照组、干扰表达IGF2BP2+6Gy辐照组对比图,其中图6A为增殖能力,图6B为细胞凋亡水平,图6C为克隆形成水平;
图7为本发明干扰表达IGF2BP2空白载体、干扰表达IGF2BP2、干扰表达IGF2BP2空白载体+6Gy辐照组、干扰表达IGF2BP2+6Gy辐照组肿瘤体积及敏感性对比图,其中图7A为瘤体体积图,图7B为敏感性对比图。
具体实施方式
为了使本发明的上述目的、特征和优点能够更加明显易懂,下面对本发明的具体实施方式做详细的说明,但不能理解为对本发明的可实施范围的限定。
实施例1检测m6A甲基化修饰水平与乳腺癌放疗抵抗的关系
收集云南省肿瘤医院放射治疗科33例局部进展期乳腺癌患者放疗前后配对新鲜组织样本,参照术后病理AJCC版肿瘤退缩分级(TumorRegressionGrade,TRG),将样本分成两组,(TRG=0+1)为放疗敏感组共18例,TRG=(2+3)为放疗抵抗组共15例。用EpiquikTMm6ARNAMethylationQuantificationKit(Colorimetric)试剂盒,检测从33例局部进展期乳腺癌患者放疗前活检组织样本中提取的总RNA。在甲基化测定过程中,总RNA被结合到RNA溶液孔底,使用捕获和检测抗体技术测定m6A甲基化水平。然后通过读取微孔板分光光度计中的吸光度进行比色定量,m6A定量与测得的OD强度成正比。要准确计算m6A绝对量,首先以OD值与每个浓度点的PC量绘制标准曲线。再使用线性回归确定标准曲线斜率(OD/ng),使用标准曲线的最线性部分(包括至少4个浓度点)进行最佳斜率计算。最后使用以下公式计算总RNA中m6A的量和百分比:m6A(ng)=(SampleOD-NCOD)/Slope;m6A%=m6AAmount(ng)/S×100%(S是样品RNA的ng数)。
实验结果如图1显示:放疗抵抗组m6A甲基化修饰水平高于放疗敏感组。
实施例2m6A甲基转移酶IGF2BP2在蛋白水平表达上调且与乳腺癌放疗抵抗呈正相关
选取33例局部进展期乳腺癌患者放疗前活检组织样本,参照术后病理AJCC版肿瘤退缩分级(TumorRegressionGrade,TRG)依次分成四组,(TRG=0)为完全敏感组,(TRG=1)为部分敏感组,(TRG=2)为部分抵抗组,(TRG=3)为完全抵抗组,Real-timePCR定量检测筛选目标m6A甲基化修饰调控因子,将组织样本离心去上清,每孔加入1000μLTrizol。每个样品中加入200μL氯仿,加入等体积异丙醇,混匀后去上清加入至少1mL4℃预冷的75%乙醇,洗涤沉淀及离心管壁。加入30-40μLRNase-free水至完全溶解,紫外分析测定RNA的浓度与吸光值。冰上配制mRNA反转录混合液。(mRNA反转录及检测试剂盒购自天根公司)将上述混合液混匀后离心获得反转录产物(cDNA)可立即用于qPCR检测。
实验结果如图2显示:m6A甲基转移酶IGF2BP2在mRNA水平表达上调,且与乳腺癌放疗抵抗呈显著正相关。
实施例3m6A甲基转移酶IGF2BP2在癌组织中高表达总生存时间缩短提示预后不良
选取33例局部进展期乳腺癌患者活检组织石蜡白片,参照术后病理AJCC版肿瘤退缩分级(TumorRegressionGrade,TRG)依次分成四组,(TRG=0)为完全敏感组,(TRG=1)为部分敏感组,(TRG=2)为部分抵抗组,(TRG=3)为完全抵抗组,用免疫组化方法通过脱蜡与水化,细胞通透与封闭抗原修复,血清封闭孵育一抗、二抗,切片显色复染及封片过程,检测m6A甲基转移酶IGF2BP2蛋白表达水平。
石蜡切片免疫组化实验操作过程如下:
1、石蜡切片脱蜡至水:依次将切片放入二甲苯Ⅰ15min、二甲苯Ⅱ15min、二甲苯III15min、无水乙醇Ⅰ5min、无水乙醇Ⅱ5min、85%酒精5min、75%酒精5min、蒸馏水洗。
2、抗原修复:组织切片置于盛满柠檬酸抗原修复缓冲液(pH6.0)的修复盒中于微波炉内进行抗原修复,中火8min至沸,停火8min保温再转中低火7min,此过程中应防止缓冲液过度蒸发,切勿干片。自然冷却后将玻片置于PBS(pH7.4)中在脱色摇床上晃动洗涤3次,每次5min。
3、阻断内源性过氧化物酶:切片放入(质量百分比浓度)3%双氧水溶液,室温避光孵育25min,将玻片置于PBS(pH7.4)中在脱色摇床上晃动洗涤3次,每次5min。
4、血清封闭:在组化圈内滴加(质量百分比浓度)3%BSA均匀覆盖组织,室温封闭30min。(一抗山羊来源用兔血清封闭,其他来源用BSA封闭)。
5、加一抗:轻轻甩掉封闭液,在切片上滴加按1:2000比例配好的一抗(IGF2BP260188-1-ig);切片平放于湿盒内,4℃孵育过夜。(湿盒内加少量水防止抗体蒸发)。
6、加二抗:玻片置于PBS(pH7.4)中在脱色摇床上晃动洗涤3次,每次5min。切片稍甩干后在圈内滴加与一抗相应种属的二抗(1:200HRP标记山羊抗小鼠二抗GB23301)覆盖组织,室温孵育50min。
7、DAB显色:玻片置于PBS(pH7.4)中在脱色摇床上晃动洗涤3次,每次5min。切片稍甩干后在圈内滴加新鲜配制的DAB显色液,显微镜下控制显色时间,阳性为棕黄色,自来水冲洗切片终止显色。
8、复染细胞核:苏木素复染3min左右自来水洗,苏木素分化液分化数秒,自来水冲洗,苏木素返蓝液返蓝,流水冲洗。
9、脱水封片:将切片依次放入75%酒精5min、85%酒精5min、无水乙醇Ⅰ5min、无水乙醇Ⅱ5min、正丁醇5min、二甲苯Ⅰ5min中脱水透明,将切片从二甲苯拿出来稍晾干,中性树胶封片。
10、显微镜镜检,图像采集分析。石蜡切片免疫组化结果判读:苏木素染细胞核为蓝色,DAB显出的阳性表达为棕黄色。
实验结果显示:甲基转移酶IGF2BP2在癌组织中高表达,癌旁组织中低表达(如图3A)。其表达水平升高,患者总生存时间缩短,提示预后不良(如图3B)。
实施例4放疗抵抗细胞模型(MCF7-R)SF2值升高获得辐照抗性
将购自ATCC乳腺癌细胞株MCF7进行小剂量(4Gy/f)梯度辐照,直至总剂量达到40Gy,获得放疗抵抗细胞模型(MCF7-R)。利用放射生物学参数(SF2值、D0、Dq)检测其与亲代细胞(MCF7)之间的差异,明确已获得辐照抗性。
实验结果如图4显示:放疗抵抗细胞模型(MCF7-R)已获得辐照抗性。
实施例5IGF2BP2在放疗抵抗细胞(MCF7-R)mRNA、蛋白表达水平升高
利用qPCR方法,检测放疗抵抗细胞(MCF7-R)及亲代细胞(MCF7),甲基转移酶IGF2BP2的mRNA表达水平。将细胞样本离心去上清,每孔加入1000μLTrizol。每个样品中加入200μL氯仿,加入等体积异丙醇,混匀后去上清加入至少1mL4℃预冷的75%乙醇,洗涤沉淀及离心管壁。加入30-40μLRNase-free水至完全溶解,紫外分析测定RNA的浓度与吸光值。冰上配制mRNA反转录混合液。(mRNA反转录及检测试剂盒购自天根生化公司)将上述混合液混匀后离心获得反转录产物(cDNA)可用于qPCR检测。
实验结果显示:IGF2BP2在MCF7-R细胞中mRNA表达水平升高(如图5A);IGF2BP2在MCF7-R细胞中WB检测蛋白表达水平升高(如图5B);IGF2BP2在MCF7-R细胞中灰度分析表达水平升高(如图5C)。
实施例6IGF2BP2干扰表达放疗抵抗MCF7-R稳转株细胞增殖能力减弱,细胞凋亡增多,克隆形成减少
选择m6A甲基转移酶IGF2BP2干扰表达放疗抵抗MCF7-R稳转细胞株,分别给予单次剂量0Gy或6Gy辐照处理。具体分组如下:干扰表达IGF2BP2空白载体(anti-NC),0Gy对照组、干扰表达IGF2BP2(anti-IGF2BP2)、干扰表达IGF2BP2空白载体+6Gy辐照组(anti-NC+IR)、干扰表达IGF2BP2+6Gy辐照组(anti-IGF2BP2+IR)。利用CCK-8、细胞凋亡、克隆形成实验,检测其放疗敏感性变化。将各组细胞消化后制成单细胞悬液计数,每组细胞配成一定浓度的单细胞悬液。每个样品设6个复孔,边缘孔加100μL无菌水。在每个检测时间点加入10μL的CCK-8于孔中无需换液,两小时后酶标仪检测450nmOD值;将细胞消化后制成单细胞悬液,每个样品准备1.0-5.0×106cells,实验组加入195μL1xbuffer然后加10μL的PI和5μLAnnexin-V-FITC染色15min结合液重悬细胞;加入400μL1xbuffer稀释,用1000μL枪轻轻混匀。将细胞移到流式上机管中,做好上机检测准备;各组细胞按6孔板每孔1000个细胞进行铺板,每组细胞铺3个复孔。每隔3天换3新鲜培养基一周后随时检查,到细胞形成克隆时终止培养。两周后染色液染色,数码相机拍照或者扫描仪扫描,计算克隆形成率。
结果显示:IGF2BP2干扰表达放疗抵抗MCF7-R稳转细胞株(anti-IGF2BP2+IR)在6Gy辐照条件下,较空白载体对照细胞株(anti-NC+IR)细胞增殖能力减弱(如图6A);IGF2BP2干扰表达放疗抵抗MCF7-R稳转细胞株(anti-IGF2BP2+IR)在6Gy辐照条件下,较空白载体对照细胞株(anti-NC+IR)细胞凋亡增多(如图6B);IGF2BP2干扰表达放疗抵抗MCF7-R稳转细胞株(anti-IGF2BP2+IR)在6Gy辐照条件下,较空白载体对照细胞株(anti-NC+IR)克隆形成减少(如图6C);提示anti-IGF2BP2能够增强乳腺癌放疗敏感性。
实施例7干扰表达IGF2BP2(MCF7-R)辐照组放疗敏感性增强
选择m6A甲基转移酶IGF2BP2干扰表达放疗抵抗(MCF7-R)稳转细胞株(anti-IGF2BP2);空白载体对照细胞株(anti-NC),挑选6只BALB/c-nu雄鼠(5-6周龄,体重>20g)皮下接种成瘤后辐照处理。具体分组如下(3只/组):干扰表达IGF2BP2空白载体(anti-NC)组、干扰表达IGF2BP2(anti-IGF2BP2)组、干扰表达IGF2BP2空白载体(anti-NC)+2Gy*3d对照组(anti-NC+IR)、干扰表达IGF2BP2(anti-IGF2BP2)+2Gy*3d实验组(anti-IGF2BP+IR)。观测瘤体体积及裸鼠体重,记录存活状态,三周后评估实验结果显示:与anti-NC+IR及anti-IGF2BP2组比较,anti-IGF2BP+IR组,瘤体体积明显缩小,放疗敏感性增强(如图7)。
最后说明的是,以上实施例仅用以说明本发明的技术方案而非限制,尽管参照较佳实施例对本发明进行了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本发明技术方案的宗旨和范围,其均应涵盖在本发明的权利要求范围。
Claims (9)
1.m6A甲基转移酶IGF2BP2在制备用于诊断乳腺癌的新辅助放疗抵抗标记物中的应用。
2.如权利要求1所述的应用,其特征在于,所述诊断乳腺癌为采用RT-qPCR技术检测乳腺癌组织样本中IGF2BP2基因的表达水平。
3.如权利要求2所述的应用,其特征在于,所述IGF2BP2基因在乳腺癌组织样品中表达上调。
4.用于诊断乳腺癌的新辅助放疗抵抗标记物在制备检测乳腺癌新辅助放疗抵抗的试剂盒、试纸或芯片中的应用,其特征在于,所述用于诊断乳腺癌的新辅助放疗抵抗标记物包括m6A甲基转移酶IGF2BP2。
5.如权利要求4所述的应用,其特征在于,所述试剂盒、试纸或芯片中,用于扩增m6A甲基转移酶IGF2BP2的基因的正向引物序列如SEQ ID NO.1所示;反向引物序列如SEQ IDNO.2所示。
6.用于诊断乳腺癌的新辅助放疗抵抗标记物在制备治疗乳腺癌的药物和/或制备调控乳腺癌新辅助放疗抵抗的药物中的应用,其特征在于,所述用于诊断乳腺癌的新辅助放疗抵抗标记物包括m6A甲基转移酶IGF2BP2。
7.根据权利要求6所述的应用,其特征在于,所述的调控为通过如下任一种方式实现:
M1:促进m6A甲基转移酶IGF2BP2表达,以增加乳腺癌放疗抵抗;
M2:抑制m6A甲基转移酶IGF2BP2表达,以降低乳腺癌放疗抵抗。
8.根据权利要求7所述的应用,其特征在于,M1中所述的促进m6A甲基转移酶IGF2BP2表达为通过在细胞内过表达m6A甲基转移酶IGF2BP2的方法实现;方式M2中所述的抑制m6A甲基转移酶IGF2BP2表达为通过试剂或药物抑制m6A甲基转移酶IGF2BP2的方法实现。
9.根据权利要求8所述的应用,其特征在于,所述试剂或药物为核酸抑制剂、蛋白抑制剂或蛋白结合分子。
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