标题：Evironmental pollutant perfluorodecanoic acid upregulates cIAP2 to suppress gastric cell senescence
作者：Zhang, Zhun; Song, Ning; Peng, Yanping; Fan, Ziyan; Han, Mingyong; Zhao, Min; Dong, Tianyi; Liu, Shili
作者机构：[Zhang, Zhun; Song, Ning; Peng, Yanping; Dong, Tianyi; Liu, Shili] Shandong Univ, Sch Basic Med Sci, Dept Med Microbiol, 44 Wenhuaxi Rd, Jinan 250012, 更多
通讯作者地址：[Liu, SL]Shandong Univ, Sch Basic Med Sci, Dept Med Microbiol, 44 Wenhuaxi Rd, Jinan 250012, Shandong, Peoples R China.
关键词：perfluorodecanoic acid; cIAP2; cell senescence; gastric cancer
摘要：The role of perfluorodecanoic acid (PFDA) in gastric carcinogenesis and its mechanism remains unknown. Our previous research revealed that PFDA regulated the growth of human gastric cells. However, its core molecules and basic mechanisms are still not clear. In the present study, cDNA microarrays were used to determine mRNA changes in AGS cells after treatment with PFDA. DAVID analysis of the genes with >2-fold increased expression in microarray data revealed five genes which were involved in cancer pathways. The most upregulated gene was cIAP2, whose upregulation in AGS was confirmed by western blot analysis and quantitative PCR (qPCR) analyses. In order to investigate the role of cIAP2 in cell proliferation, cIAP2 siRNA was employed to regulate cIAP2 expression following PFDA treatment. The results revealed that the growth rate of cIAP2-knockdown cells was reduced by about 50% compared to the control. Given that our previous flow cytometric assays revealed no significant change (3.7 vs. 6.4%) in the percentage of apoptotic cells when PFDA was added to the medium and cIAP2 expression was upregulated, we next applied flow cytometry to assess whether cIAP2 would lead to cell cycle variations. The research data revealed that the proportion of cells in the G1, S and G2 phases was not significantly altered with the decrease of cIAP2 expression. Finally, the role of cIAP2 in AGS cell senescence was investigated, and the results indicated that cell senescence was significantly increased in the cIAP2 siRNA group in comparison to the control siRNA group. Since p53 has been identified as a tumor suppressor and its molecular alterations are common in different human tumors, we investigated the relationship of p53 with cIAP2. The experimental results demonstrated that cIAP2 regulated the expression of p53 and thus was likely to be a potential mechanism for PFDA-induced growth promotion. Overall, the results revealed that PFDA may suppress cellular senescence induced by p53 through the regulation of cIAP2 protein expression.