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Background AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor suppressor protein. The loss of ARID1A been observed in several types of human cancers and associated with poor patient prognosis. Previously, we have reported that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer cells during DNA damage response. However, the ubiquitin e3 ligase that mediated this process remains unclear. Materials and methods The interaction between ARID1A and β-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin RNAs (shRNAs) were used to knockdown (KD) gene expression. Results Here we show that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the ubiquitin E3 ligase complex SCFβ-TRCP. β-TRCP recognizes ARID1A through a canonical degron site (DSGXXS) after its phosphorylation in response to DNA damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase impaired DNA damage-induced ARID1A destruction. Conclusions Our studies provide a novel molecular mechanism for the negative regulation of ARID1A by β-TRCP and ATM in DNA damaged gastric cancer cells.

Background Interleukin-4(IL-4) is a critical inflammatory cytokine and has been involved in pathogenesis of cancer. To date, several studies have investigated the association between IL-4 intron 3 variable number of tandem repeats (VNTR) polymorphism and cancer risk in humans; however, the results remain controversial. We performed this meta-analysis to find a more conclusive association between this polymorphism and cancer risk. Methods Eight eligible case–control studies were identified through searching electronic databases, including 1583 cases and 1638 controls. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate the strength of the association. Results The results of overall analyses indicated that the variant RP2 allele was associated with a decreased cancer risk compared with the RP1 allele (RP2/RP2 vs. RP1/RP1, OR = 0.64, 95% CI = 0.44-0.94; RP2/RP2 vs. RP1/RP1 + RP1/RP2, OR = 0.75, 95% CI = 0.60-0.92; RP2 vs. RP1, OR = 0.72, 95% CI = 0.56-0.92). In subgroup analyses stratified by ethnicity, there was evidence in the Asian population for an association between this polymorphism and cancer risk (RP2/RP2 vs. RP1/RP1 + RP1/RP2, OR = 0.79, 95% CI = 0.63-0.99; RP2 vs. RP1, OR = 0.77, 95% CI = 0.61-0.97). Conclusions IL-4 intron 3 VNTR polymorphism could influence the risk of human cancer. Due to the limitations of this meta-analysis, further well-designed and functional researches should be performed to validate our results.