ARHI在肿瘤发生和发展中的作用与机制研究进展

Progress in the role and mechanism of ARHI in tumorigenesis and development

ARHI是1999年发现的母源性印迹基因,属于小G蛋白Ras超家族,是该家族第1个被报道的抑癌基因。ARHI的功能包括抑制小鼠生长和生殖发育,抑制细胞增殖、迁移,参与周期调控和凋亡,近年来研究发现ARHI还具有调控肿瘤细胞自噬、抑制肿瘤转移的作用。ARHI蛋白在人体卵巢、乳腺等多种组织中表达,在卵巢癌、乳腺癌、甲状腺癌、胰腺癌、肝癌组织中表达下调,ARHI基因高表达可提示卵巢癌、胰腺癌的预后良好。ARHI表达调控机制包括杂合性丢失、DNA甲基化、组蛋白去乙酰化、转录因子调节、miRNA和突变,应用表观遗传学技术调节ARHI表达可能在一些肿瘤中具有抗肿瘤临床应用价值。ARHI基因参与调节肿瘤细胞休眠过程,有望成为诱导肿瘤细胞休眠、抗肿瘤转移复发的关键点。

ARHI is a maternally imprinted gene discovered in 1999,belongs to small G proteins Ras superfamily.ARHI is the first tumor suppressor gene to be reported in Ras superfamily.A family is the first to be reported in the tumor suppressor gene.The functions of ARHI include inhibition of the growth and reproductive development in mice,inhibition of proliferation and migration,and involvement in cell cycle regulation and apoptosis.Recent studies have also found that ARHI regulated autophagy in tumor cells and inhibited tumor metastasis.ARHI protein was expressed in human ovarian,breast and other tissues,and was downregulated in ovarian cancer,breast cancer,thyroid cancer,pancreatic cancer,hepatocellular carcinoma,and high expression of ARHI gene might suggest a good prognosis in ovarian cancer and pancreatic cancer.The regulation mechanisms of ARHI expression include loss of heterozygosity,DNA methylation,histone acetylation,transcriptional factor regulation,miRNA and mutation.The epigenetic regulation of ARHI expression might have anti-tumor clinical value for some tumors.ARHI gene involved in the regulation of ovarian cancer cell dormancy process is expected to become a key point of inducing tumor cell dormancy and anti-metastatic recurrence.