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在乳腺上皮细胞中由APOBEC3酶诱导的类似的除活动,但具有不同的表型结果

Milaid Granadillo Rodríguez¹, Lai Wong¹, Linda Chelico¹

¹Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.

Frontiers in genome editing

|June 16, 2023

概括

APOBEC3 (A3) 酶会在乳腺细胞中引起DNA损伤,但它们在癌症中的具体作用尚不清楚. 这项研究揭示了A3A,A3B和A3H的独特细胞效应,突出了对癌症表型的不同影响.

科学领域:

遗传学遗传学是一个
分子生物学分子生物学
癌症研究癌症研究

背景情况:

APOBEC3 (A3) 酶对抗病毒的天生的免疫力至关重要,因为它通过在病毒DNA中去胺化细胞素.
在人类基因组中,A3诱导的突变也存在内源性,有助于各种癌症的体质突变.
单个A3酶在癌症发展中的特定作用和突变性潜力在很大程度上仍未被描述.

研究的目的:

研究和比较乳腺上皮细胞中A3A,A3B和A3H Hap I的突变性潜力和与癌症相关的表型.
为了确定体外除活动是否与细胞DNA损伤和功能结果相关.
阐明每个A3酶在非瘤原生和瘤原生乳腺细胞环境中的独特细胞影响.

主要方法:

在MCF10A和MCF7细胞中开发出表达A3A,A3B或A3H Hap I的稳定细胞系.
通过γH2AX焦点形成和体外除氨测试来评估DNA损伤.
使用细胞迁移和软菌殖民地形成试验评估细胞转化.

主要成果:

这三种A3酶都诱导了类似的DNA损伤水平 (γH2AX焦点),尽管体外除活性有所不同.
在核溶解酸中A3A,A3B和A3H的体外除氨酶活性不需要RNA消化,与全细胞溶解酸不同.
观察到不同的细胞表型:A3A抑制了软菌殖民地形成,A3B在基尿素治疗后这样做,A3H促进了细胞迁移.

结论:

在体外除毒数据并不总是准确地预测细胞DNA损伤或功能结果.
所有三个研究的APOBEC3酶都会诱导乳腺细胞中的DNA损伤.
每个A3酶对细胞表型产生独特的影响,这表明它们在乳腺癌的发展和进展中扮演着不同的角色.

关键词:

在 APOBEC3 中,APOBEC3 是造成的DNA损伤是DNA损伤.癌症癌症癌症癌症癌症缺乏氨基酸酶的方法酶活性的酶活动.

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