Abstract:
ARHI (aplasia ras homologue member I)/NOEY2 is a novel maternally imprinted tumor suppressor gene discovered in 1999. It is located in human chromosome 1p31. The ARHI gene encodes a 26 kDa small GTP-binding protein. It is a member of ras/rap superfamily, which has 50%-60% homology and share similar GTP/GDP-binding domains with the ras/rap superfamily. Unlike other members, however, it acts as a tumor suppressor gene and is the first reported tumor suppressor gene in the ras/rap family. The ARHI gene encodes protein that is widely expressed in most types of human tissues, but it often reduced or absent in human ovarian, breast, pancreas, and liver cancer, and other tumors, which suggests that it is closely related to the occurrence and development of tumors. Affecting cyclin D1, ARHI is a negative regulator of the cell cycle and blocks the cell growth at the G1 phase. ARHI induces cell apoptosis through the caspase and calpain cell signal transduction pathway. In addition, the ARHI gene functions as a tumor suppressor gene by inhibiting the activation of STAT3. It also regulates autophagy and tumor dormancy. Studies have shown that the loss of ARHI expression can occur through genetic events and epigenetic mechanisms, including DNA aberrant methylation, loss of heterozygosity, low-level expression of acetylation histone, and gene mutation. This issue needs further research. Further studies on the ARHI gene will provide new ideas and theories for the early diagnosis and treatment of tumors.