抑制肿瘤小G蛋白ARHI研究进展

Research Progress of ARHI,a Small GTP Binding Protein,Related to Tumor Repressing

小GTP结合蛋白在细胞的整个生命活动中起着重要的作用.人类ARHI基因是小GTP结合蛋白中Ras亚家族的一个成员,系母系印迹基因,定位于染色体1p3l.ARHI基因含有两个外显子和一个内含子,启动子区域有转录抑制因子E2F结合位点、3’末端有Au-rich区域.在ARHI基因中存在三个CpG岛,其中第一个CpG岛位于该基因的启动子区域,第二个CpG岛跨越了启动子和第一个外显子区,第三个CpG岛处于第二个外显子之内.与正常细胞相比,ARHI基因在肿瘤细胞中表达受到抑制,其原因为ARHI基因的杂合缺失,CpG岛的异常甲基化,转录抑制因子增多和多聚组蛋白脱乙酰化酶表达加强等.ARHI通过需钙蛋白酶途径诱导细胞凋亡;通过与STAT3(信号转导与转录激活因子3)的结合阻滞癌变.

Small GTP binding proteins play an important role in the life of cell. ARHI is a member of the Ras subfamily and an imprinting gene localized in chromosome 1 p31. There are two exons and one intron in the ARHI gene, including transcriptional repress factor E2F binding site and AU-rich elements in the 3＇ UTR. Three potential CpG islands are identified, two of them（CpG island Ⅰ and Ⅱ ）located within the promoter and adjacent exon 1 of the ARHI gene and the third one（CpG island Ⅲ） situated in the second exon. Compared with normal cells, ARHI is repressed in tumor cells resulting from loss of heterozygosity, aberrant methylation of CpG island, increasing of transcriptional repress factors and enhancing expression of multiple histone deacetylases. ARHI induces cell apoptosis by calpain-dependent pathway and prevents cells from canceration by binding with signal transducers and activators of transcription 3 （STAT3）.