VHL基底转录因子ZHX2作为清细胞癌的致癌因子
Jing Zhang1,2, Tao Wu3, Jeremy Simon1,4
1Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Science (New York, N.Y.)
|July 21, 2018
概括
希佩尔- 林道 (VHL) 蛋白质的损失导致清细胞癌 (ccRCC). 研究人员确定ZHX2为VHL标,揭示ZHX2是ccRCC的潜在治疗标.
科学领域:
- 癌症学
- 分子生物学
- 生物化学
背景情况:
- 希佩尔- 林道 (VHL) E3 泛素结合酶的失活是清细胞细胞癌 (ccRCC) 发病的一个关键事件.
- 了解受VHL损失影响的下游途径对于开发有效的ccRCC疗法至关重要.
研究的目的:
- 在化过程中与VHL相互作用的蛋白质.
- 调查已确定的VHL目标在ccRCC发展和进展中的作用.
- 探索ZHX2作为ccRCC的潜在治疗点.
主要方法:
- 基因组范围内的体外表达查以确定VHL结合蛋白.
- 通过VHL对ZHX2蛋白稳定性调节的评估
- 在ccRCC患者的瘤中分析ZHX2的丰度和定位.
- 在体外和体内功能测定涉及ZHX2耗尽.
- 综合色素免疫沉测序和微阵列分析以阐明分子机制.
主要成果:
- 指和2 (ZHX2) 被确定为一个VHL目标,其化使VHL介导的蛋白质稳定性调节.
- 在具有VHL突变的ccRCC瘤细胞中观察到增加的ZHX2丰度和核定位.
- 在体外和体内,ZHX2的耗尽显著抑制了缺乏VHL的ccRCC细胞的生长.
- 发现ZHX2可以促进核因子 κB (NF-κB) 的激活.
结论:
- ZHX2 是一种涉及ccRCC的新型VHL标蛋白.
- 在促进ccRCC细胞生长和NF-κB激活方面,ZHX2发挥着关键作用.
- 在ccRCC治疗中,ZHX2是一个有前途的治疗点.
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