TARDBP通过结合MDM2mRNA,涉及β-catenin通路,驱动T细胞急性淋巴细胞白血病的进展
Yumiao Mai1, Zhaohe Jing1, Pan Sun1
1Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
概括
转激活反应DNA结合蛋白 (TARDBP) 在T细胞急性淋巴细胞白血病 (T-ALL) 中高度表达. 沉默TARDBP会抑制T-ALL的生长,而其过度表达会促进它,这表明TARDBP是潜在的T-ALL生物标志物.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- T细胞急性淋巴细胞白血病 (T-ALL) 是一种严重的血液性恶性瘤.
- 转激活反应DNA结合蛋白 (TARDBP) 与各种癌症有关,但其在T-ALL中的作用以前没有报告.
- 微阵列分析 (GSE26713) 在儿科T-ALL样本中显示出高TARDBP表达.
研究的目的:
- 调查T-ALL中TARDBP的作用和机制.
- 探索TARDBP作为T-ALL的潜在治疗生物标志物.
- 阐明T-ALL中β-catenin通路TARDBP与MDM2之间的关系.
主要方法:
- 在T-ALL细胞系 (Jurkat,Molt4) 中,TARDBP被静止和过度表达,使用了lentivirus转导.
- 在体外测试中评估了细胞增殖,循环进展和细胞亡.
- 在体内研究涉及向小鼠注射改性T-ALL细胞.
- 使用RIP-PCR和mRNA-seq来研究分子相互作用和途径.
主要成果:
- 沉默TARDBP抑制T-ALL细胞增殖和诱导亡;过度表达具有相反的效果.
- TARDBP促进了小鼠脏和骨髓中的T-ALL生长.
- 发现TARDBP与MDM2相关,并在T-ALL细胞中与MDM2mRNA结合.
- 涉及β-catenin通路,由XAV-939抑制抑制恶性表型.
结论:
- 在T-ALL进展和恶性瘤中,TARDBP起着至关重要的作用.
- 在T-ALL中,TARDBP/MDM2轴和β-catenin通路调节是T-ALL的关键机制.
- TARDBP是一个有前途的生物标志物和T-ALL治疗的潜在治疗标.
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