RGD Reference Report - Evironmental pollutant perfluorodecanoic acid upregulates cIAP2 to suppress gastric cell senescence. - Rat Genome Database

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Evironmental pollutant perfluorodecanoic acid upregulates cIAP2 to suppress gastric cell senescence.

Authors: Zhang, Zhun  Song, Ning  Peng, Yanping  Fan, Ziyan  Han, Mingyong  Zhao, Min  Dong, Tianyi  Liu, Shili 
Citation: Zhang Z, etal., Oncol Rep. 2019 Feb;41(2):981-988. doi: 10.3892/or.2018.6856. Epub 2018 Nov 9.
RGD ID: 152998989
Pubmed: PMID:30431128   (View Abstract at PubMed)
DOI: DOI:10.3892/or.2018.6856   (Journal Full-text)

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.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
perfluorodecanoic acid increases expression EXP 152998989Perfluorodecanoic acid increases expression of BIRC3 mRNA and protein in gastric adenocarcinoma cellsRGD 
perfluorodecanoic acid increases expression ISOBIRC3 (Homo sapiens)152998989; 152998989Perfluorodecanoic acid increases expression of BIRC3 mRNA and protein in gastric adenocarcinoma cellsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Birc3  (baculoviral IAP repeat-containing 3)

Genes (Mus musculus)
Birc3  (baculoviral IAP repeat-containing 3)

Genes (Homo sapiens)
BIRC3  (baculoviral IAP repeat containing 3)


Additional Information