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Activation-Induced Cytidine Deaminase Expression Facilitates the Malignant Phenotype and Epithelial-to-Mesenchymal Transition in Clear Cell Renal Cell Carcinoma.
DNA and Cell Biology ( IF 3.1 ) Pub Date : 2020-07-02 , DOI: 10.1089/dna.2019.5119
Zhifei Che 1 , Jinfeng Fan 1 , Zhiyan Zhou 1 , Qi Li 2 , Zhe Ma 1 , Zhanhao Hu 1 , Yaoxi Wu 1 , Yingxia Jin 2 , Yang Su 2 , Peiyu Liang 1 , Haoyong Li 2
Affiliation  

Although advances have been made in the development of antiangiogenesis targeted therapy and surgery, metastatic clear cell renal cell carcinoma (ccRCC) is still incurable. Activation-induced cytidine deaminase (AID) is mainly expressed in a variety of germ and somatic cells, and induces somatic hypermutation and class-switch recombination, playing a vital role in antibody diversification. We confirmed that AID was expressed at a higher level in ccRCC tissues than in the corresponding nontumor renal tissues. We explored the impact of AID on ccRCC proliferation, invasion, and migration. In 769-p and 786-0 cells, expression of an AID-specific short hairpin RNA significantly reduced AID expression, which markedly inhibited tumor cell invasion, proliferation, and migration. Previous studies showed that AID is associated with Wnt ligand secretion mediator (WLS/GPR177), cyclin-dependent kinase 4 (CDK4), and stromal cell-derived factor-1 (SDF-1/CXCL12) regulation, which was further confirmed in human ccRCC tissues. Therefore, we studied the relationship between AID and these three molecules, and the impact of AID on epithelial-to-mesenchymal transition in ccRCC. WLS/GPR177, SDF-1/CXCL12, and CDK4 were sensitive to 5-azacytidine (a DNA demethylation agent), which reverted the inhibition of carcinogenesis caused by AID repression. In summary, AID is an oncogene that might induce tumorigenesis through DNA demethylation. Targeting AID may represent a novel therapeutic approach to treat metastatic ccRCC.

中文翻译:

激活诱导的胞苷脱氨酶表达促进透明细胞肾细胞癌的恶性表型和上皮向间充质转化。

尽管在抗血管生成靶向治疗和手术的开发方面已取得进展,但转移性透明细胞肾细胞癌(ccRCC)仍无法治愈。激活诱导的胞苷脱氨酶(AID)主要在多种生殖细胞和体细胞中表达,并诱导体细胞超突变和类别转换重组,在抗体多样化中起着至关重要的作用。我们证实,ccIDC组织中AID的表达水平高于相应的非肿瘤肾组织。我们探讨了AID对ccRCC增殖,入侵和迁移的影响。在769-p和786-0细胞中,AID特异性短发夹RNA的表达显着降低了AID表达,从而显着抑制了肿瘤细胞的侵袭,增殖和迁移。先前的研究表明AID与Wnt配体分泌介体(WLS / GPR177),细胞周期蛋白依赖性激酶4(CDK4)和基质细胞衍生因子1(SDF-1 / CXCL12)调节有关,这一点在人类中得到了进一步证实ccRCC组织。因此,我们研究了AID与这三个分子之间的关系,以及AID对ccRCC中上皮到间充质转化的影响。WLS / GPR177,SDF-1 / CXCL12和CDK4对5-氮杂胞苷(一种DNA去甲基化剂)敏感,从而恢复了对AID抑制所致癌变的抑制作用。总之,AID是一种癌基因,可能通过DNA脱甲基作用诱导肿瘤发生。靶向AID可能代表一种治疗转移性ccRCC的新颖治疗方法。在人ccRCC组织中进一步证实了这一点。因此,我们研究了AID与这三个分子之间的关系,以及AID对ccRCC中上皮到间充质转化的影响。WLS / GPR177,SDF-1 / CXCL12和CDK4对5-氮杂胞苷(一种DNA去甲基化剂)敏感,从而恢复了对AID抑制所致癌变的抑制作用。总之,AID是一种癌基因,可能通过DNA脱甲基作用诱导肿瘤发生。靶向AID可能代表一种治疗转移性ccRCC的新颖治疗方法。在人ccRCC组织中进一步证实了这一点。因此,我们研究了AID与这三个分子之间的关系,以及AID对ccRCC中上皮到间充质转化的影响。WLS / GPR177,SDF-1 / CXCL12和CDK4对5-氮杂胞苷(一种DNA去甲基化剂)敏感,从而恢复了对AID抑制所致癌变的抑制作用。总之,AID是一种癌基因,可能通过DNA脱甲基作用诱导肿瘤发生。靶向AID可能代表一种治疗转移性ccRCC的新颖治疗方法。从而逆转了由AID抑制所致癌变的抑制作用。总之,AID是一种癌基因,可能通过DNA脱甲基作用诱导肿瘤发生。靶向AID可能代表一种治疗转移性ccRCC的新颖治疗方法。从而逆转了由AID抑制所致癌变的抑制作用。总之,AID是一种癌基因,可能通过DNA脱甲基作用诱导肿瘤发生。靶向AID可能代表一种治疗转移性ccRCC的新颖治疗方法。
更新日期:2020-07-10
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