RESUMEN
CDT1, a gene that shows excessive expression in various malignancies, functions as a pivotal regulator of replication licensing. In this study, we observed a positive correlation in expression between CDT1 and E2F2 among patients with lung adenocarcinoma (LUAD). Our findings substantiated that E2F2 directly interacted with the promoter region of CDT1, as confirmed by ChIP-qPCR assays, and depletion of E2F2 resulted in a downregulation of CDT1 expression in LUAD cell lines by gene interference technology. Furthermore, we identified an upregulation of CDT1 mRNA level in Chinese LUAD samples. Notably, in the loss-of-function assays, depletion of CDT1 in LUAD cell lines inhibited cell proliferation, migration, and invasion. Concurrently, it promoted cell apoptosis and induced G0/G1 phase arrest using MTT, flow cytometry, and Transwell assays, reinforcing its role as an oncogene.Furthermore, enhanced tumor ablation was determined in a CDT1-downregulated LUAD tumor-bearing nude mouse model. Collectively, our results strongly suggest that E2F2 positively regulates CDT1 expression and actively participates in the progression of lung adenocarcinoma, thereby providing valuable insights into identifying novel therapeutic targets for LUAD treatment.
RESUMEN
BACKGROUND/AIM: Endometrial cancer (EC) is a frequent gynecological cancer. Studies have demonstrated that the sensitivity of EC toward 5-fluorouracil (5-FU) chemotherapy has decreased, leading to unsatisfactory treatment effects. There is an urgent need to investigate the reasons for the unsatisfactory treatment of EC with 5-FU. The purpose of the study was to investigate the effect of RAD51AP1 after being transcriptionally activated by E2F7 on the sensitivity of EC cells to 5-FU chemotherapy via the fatty acid metabolic pathway. MATERIALS AND METHODS: mRNA expression data on EC were downloaded from The Cancer Genome Atlas database, subjected to differential expression analysis, and the target genes were determined based on the bioinformatics analysis and literature consulting. The regulatory transcription factor upstream of RAD51AP1 in EC was predicted using the hTFtarget database. The expression of E2F7 and RAD51AP1 was measured by qRT-PCR and western blot. Then, the transcriptional activation relationship between E2F7 and RAD51AP1 was verified by chromatin immunoprecipitation (ChIP) and dual luciferase assays. The IC50 values of EC cells toward 5-FU were determined by the CCK-8 assay, and cell apoptosis was detected by flow cytometry. The expression of apoptosis-related and fatty acid metabolism-related proteins was evaluated by western blot. RESULTS: Bioinformatics analysis showed that both E2F7 and RAD51AP1 were highly expressed in EC, and the possible binding sites between RAD51AP1 promoter and E2F7 were predicted. ChIP assay and dual luciferase assay confirmed the binding of E2F7 to RAD51AP1 promoter region. Cell experiments showed that overexpressing RAD51AP1 could facilitate the growth and fatty acid metabolism of EC cells, and suppress cell sensitivity to 5-FU, while silencing of E2F7 could reduce the effect of RAD51AP1 overexpression on EC cell growth and sensitivity toward 5-FU. CONCLUSION: The E2F7/RAD51AP1 axis can promote the growth of EC cells and inhibit cell sensitivity to 5-FU by regulating fatty acid metabolism, suggesting that E2F7/RAD51AP1 axis may be a novel pathway for EC treatment.