Background Tripartite motif (TRIM) proteins have been proved to contribute to cancer progression, while whether tripartite motif‐containing 54 (TRIM54) could functionally influence gastric cancer (GC) progression remains elusive. Methods The expression level of TRIM54 and filamin C (FLNC) in GC was determined by Western blot and online database. Cell Counting Kit‐8 (CCK‐8) assay, colony formation assay and Ethylenediurea (EdU) staining were performed to explore the effects of TRIM54 on GC cell proliferation. Transwell assay and wound healing assay were applied to detect the influence of TRIM54 on GC cell migration and invasion. Bioinformatics analysis and Co‐immunoprecipitation assay (Co‐Ip), Ubiquitination assay and Half‐life assay were involved to explore the regulatory mechanism of TRIM54 on FLNC. Results TRIM54 was upregulated in GC tissues and cells, and a higher expression level of TRIM54 indicated a shorter overall survival of GC patients. The overexpression of TRIM54 significantly enhanced proliferation, migration, and invasion of GC cells, and inhibition of TRIM54 expression exerted reverse effects on GC cells. Mechanistically, TRIM54 was determined as a post‐translational mediator of FLNC, and TRIM54 was co‐immunoprecipitated with FLNC and degraded its protein level via K63‐linked ubiquitination of FLNC. Notably, FLNC efficiently inhibited GC progression by TRIM54 overexpression. Conclusion Collectively, our findings suggested that the TRIM54/FLNC axis could be considered as a potential prognostic biomarker for GC.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Cisplatin-based chemotherapy currently represents the main treatment option for patients with NSCLC. The aim of the present study was to evaluate effect of single nucleotide polymorphisms (SNPs) within the excision repair cross-complementing group 5 (ERCC5) gene on susceptibility to NSCLC, as well as the responsiveness to and toxicity of cisplatin chemotherapy. A total of 506 patients with NSCLC and 510 healthy controls were recruited for the present study. All DNA samples were genotyped by the Agena MassARRAY platform. Logistic regression analysis was carried out to assess the relationship between ERCC5 polymorphisms with NSCLC susceptibility and responsiveness to chemotherapy. The rs4771436 TG-GG genotype was associated with increased NSCLC risk. When the data were stratified according to age, sex, tobacco smoking, body mass index and histological type, ERCC5 polymorphisms (rs2016073, rs4771436, rs11069498 and rs4150330) were associated with NSCLC risk. Furthermore, the A allele and GA-AA genotype of rs11069498 were related to the response to chemotherapy. ERCC5 (rs11069498 and rs4150330) polymorphisms were associated with the increased risk of toxicity. However, rs4771436 in ERCC5 gene was significantly correlated with the reduced risk of toxicity. These results suggested a potential relationship between ERCC5 polymorphisms, the risk of NSCLC and the sensitivity to cisplatin-based chemotherapy among Chinese populations.
Background: Non-small cell lung cancer (NSCLC) accounts for approximately 80% of diagnosed lung cancer patients. RAD52 has been reported to be associated with the development of squamous cell lung carcinoma. In this study, we assessed the relationships of RAD52 genetic polymorphisms and NSCLC risk among the Chinese population at high altitude. Methods: Eight single nucleotide polymorphisms (SNPs) of RAD52 were genotyped in the Agena MassARRAY platform among 506 NSCLC patients and 510 healthy controls. We examined the association of RAD52 polymorphisms with NSCLC risk using odds ratios (ORs) and 95% confidence intervals (CIs) via multiple genetic models. Results: The rs10774474 A allele was related to a decreased risk of NSCLC in a high altitude population of China (OR = 0.82, 95% CI = 0.69–0.98, p = 0.032), whereas mutant alleles of rs1051672, rs7310449, rs1051669, rs6413436, rs4766377 and rs10849605 significantly increased NSCLC risk. Haplotype analysis showed that four haplotypes of RAD52 polymorphisms conferred an enhanced susceptibility to NSCLC (Ars1051672Grs7310449Trs1051669Ars6413436: OR = 1.29, p = 0.021; Grs1051672Ars7310449Crs1051669Grs6413436: OR = 1.21, p = 0.027; Grs4766377Crs12822733Trs10774474Crs10849605: OR = 1.26, p = 0.032; Ars4766377Crs12822733Ars10774474Trs10849605: OR = 1.21, p = 0.032). Conclusions: Our findings suggested the remarkable association of RAD52 polymorphisms with NSCLC risk among the Chinese population in a high altitude area. The reviews of this paper are available via the supplemental material section.
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