J Cell Bio：一个基因能遏制乳腺癌

近日，日本一个研究小组日前发布研究成果说，具有肿瘤抑制作用的乳腺癌易感基因BRCA1除可通过修复染色体异常来遏制乳腺癌和卵巢癌外，还能通过生成小核糖核酸来遏制癌症。这一成果可协助研究人员开发出新治疗药物。
 
乳腺癌易感基因BRCA1是近年来发现的一个肿瘤抑制基因，它的结构和功能变化与家族型乳腺癌和卵巢癌的发生有关。研究证实，BRCA1基因发生突变的人在40岁以前得乳腺癌的概率高达19%。
 
日本大阪大学特聘副教授河合伸治率领的研究小组在美国《细胞生物学期刊》The Journal of Cell Biology发表报告说，他们调查人类细胞中与抑制癌症有关的4种小核糖核酸的量时发现，如果加强细胞中BRCA1基因的作用，这些小核糖核酸的量会增加，而如果抑制这一基因的作用，这些小核糖核酸的量则减少。显示两者具密切关系。
 
河合伸治说：“很多癌症中都发现了小核糖核酸的异常。这些异常有可能与BRCA1基因有关，这一发现有可能协助研究人员开发出新的治疗药物。”

doi:10.1083/jcb.201110008
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BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex

Shinji Kawai1 and Atsuo Amano2

MicroRNAs (miRNAs) are noncoding RNAs that function as key posttranscriptional regulators of gene expression. miRNA maturation is controlled by the DROSHA microprocessor complex. However, the detailed mechanism of miRNA biogenesis remains unclear. We show that the tumor suppressor breast cancer 1 (BRCA1) accelerates the processing of miRNA primary transcripts. BRCA1 increased the expressions of both precursor and mature forms of let-7a-1, miR-16-1, miR-145, and miR-34a. In addition, this tumor suppressor was shown to be directly associated with DROSHA and DDX5 of the DROSHA microprocessor complex, and it interacted with Smad3, p53, and DHX9 RNA helicase. We also found that BRCA1 recognizes the RNA secondary structure and directly binds with primary transcripts of miRNAs via a DNA-binding domain. Together, these results suggest that BRCA1 regulates miRNA biogenesis via the DROSHA microprocessor complex and Smad3/p53/DHX9. Our findings also indicate novel functions of BRCA1 in miRNA biogenesis, which may be linked to its tumor suppressor mechanism and maintenance of genomic stability.