抑癌基因ARID1A在肿瘤中的研究进展

Tumor Suppressor Gene ARID1A in Cancers

染色质重塑复合物相关基因在癌症中频繁突变,这种现象逐渐引起研究者的重视。然而,染色质重塑活动如何引起癌症发生,对此机理研究甚少。ARID1A是SWI/SNF(BRG1相关因子)染色质重塑复合物中的一个亚基,具有DNA结合活性,可以与富含AT的DNA序列特异性结合。近来基因组测序发现,ARID1A在卵巢癌、肝癌、胃癌、乳腺癌等肿瘤中频繁发生突变,这些突变导致ARID1A在肿瘤中表达降低,表明ARID1A是个潜在的抑癌基因。该文将针对ARID1A在各种癌症中的缺失及失活机制、ARID1A的生物学功能和潜在抑癌机理以及与临床预后之间关系等方面做一综述,以期为肿瘤诊断、治疗提供新思路。

Chromatin remodeling complex genes are found to be frequently mutated in a variety of human cancers. However, the mechanisms by which chromatin remodeling complexes contribute to the cancer phenotype are poorly understood. ARID 1 A （AT-rich interactive domain-containing protein 1A） is a large subunit of SWI/SNF （BRGl-associated factors） chromatin remodeling complex. ARID1A has a DNA-binding domain that can specifi- cally bind an AT-rich DNA sequence. Recent exome sequencing studies reveal that ARID1A is frequently mutated in carcinomas, including ovarian, liver, gastric and breast cancers. These mutations cause the reduced expression of ARID1A in cancers, which indicates that ARID1A might be a tumor suppressor. Here, we review recent studies of ARID1A mutation and low expression in cancers. We summarize the novel findings on the biological functions and the regulatory tumor-suppressing mechanisms of ARID1A. We also review the discoveries of the relationship be- tween ARID 1 A mutations and clinic prognosis. Our review will provide beneficial information for the development of new antitumor diagnosis and therapy.