Gene C9orf100 And Stc2 In Its Role In The Development Of Cancer Of The Liver And Its Mechanism Is Discussed

The research content includes two aspects:The first part:To explore the role and mechanism of C9orf100, a new member of Dbl-family guanine nucleotide exchange factors, in hepatocellular carcinoma carcinogenesis. Using high-throughput genomics technologies for gene expression profiling analysis on liver cancer samples, we found that the gene C9orfl00expression is upregulated in all22cases of HCC samples. The PCR experimental date of C9orf100gene expression in HCC samples verify the results of the above gene cliip. Among the44pairs of clinical samples,42/44displayed at least a two-fold increase. Analysing the correlation between the gene mRNA expression levels and clinicopathological characteristics in patients, we found C9orfl00mRNA levels were higher in samples with multiple tumors than those with single tumor, with serum a-fetoprotein level (AFP)≥10ng/ml than those<10ng/ml, with cirrhosis than non-cirrhosis. In addition, immunofluorescence assay confirmed C9orfl00protein localized to cell membrane or near the membrane. Futher experiments proved C9orf100overexpression could promote cell proliferation of HCC cells. In contrast, silencing of C9orf100by siRNA resulted in a suppression of cell growth. Meantime, flow cytometry analysis confirmed decreased C9orfl00expression resulted in cell cycle arrested in G2/M phase and cell apoptosis. Finally, we found the activity of AKT increased after overexpression of C9orfl00in Huh7cells. On the contrary, silencing of C9orfl00expression in MHCC-97H cells, AKT activity was significantly decreased. Our latest research results show C9orfl00affects HCC cell proliferation by regulating cell cycle distribution and apoptosis, and plays an import(?)nt role in cell migration.The second part:Stanniocalcin2as a member of the Stanniocalcin protein family members, has been reported to participate in the formation of some tumors. Among the44pairs of clinical samples,35/44(79.5%) showed STC2upregulation in HCC cancer tissues compared with the matched adjacent tissues. Silencing of endogenous STC2expression resulted in a reduced cell growth, colony formation and mirgration ability. While ectopic expression of STC2markedly promoted HCC cell proliferation and migr ation. Futher, flow cytometry analysis confirmed silencing of C9orf100expression resulted in cell cycle arrested in Go/G1phase. Western blot analysis demon strated that protein cyclin D1and activate extracellular signal-regulated kinase/2(ERK1/2) play an important role in cell cycle regulation. The results indicate that gene STC2plays an oncegenic role in the process of HCC carcinogenesis.