E2F7

Lymphatic system distributes in almost all vertebrate tissues and organs, and plays important roles in the regulation of body fluid balance, lipid absorption and immune monitoring. Although CuNPs or AgNPs accumulation has been reported to be closely associated with delayed hatching and motor dysfunction in zebrafish embryos, their biological effects on lymphangiogenesis remain unknown. In this study, thoracic duct was observed to be partially absent in both CuNPs and AgNPs stressed zebrafish larvae. Specifically, CuNPs stress induced hypermethylation of E2F7/8 binding sites on CCBE1 promoters via their producing ROS, thereby leading to the reduction of binding enrichment of E2F7/8 on CCBE1 promoter and its subsequently reduced expression, then resulting in defective lymphatic vessel formation. Differently, AgNPs stress induced down-regulated CCBE1 expression via down-regulating mRNA and protein levels of E2F7/8 transcription factors, thereby resulting in defective lymphatic vessel formation. This study may be the first to demonstrate that CuNPs and AgNPs damaged lymphangiogenesis during zebrafish embryogenesis, mechanistically, CuNPs epigenetically regulated the expression of lymphangiogenesis regulator CCBE1 via hypermethylating its promoter binding sites of E2F7/8, while AgNPs via regulating E2F7/8 expression. Meanwhile, overexpression of ccbe1 mRNA effectively rescued the lymphangiogenesis defects in both AgNPs and CuNPs stressed larvae, while overexpression of e2f7/8 mRNA effectively rescued the lymphangiogenesis defects in AgNPs rather than CuNPs stressed larvae. The results in this study will shed some light on the safety assessment of nanomaterials applied in medicine and on the ecological security assessments of nanomaterials. Video Abstract.

Adriamycin resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer.

Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot.

In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells.

E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.

E2F transcription factors (E2Fs) are a family of transcription factors critical regulators of the cell cycle, apoptosis, and differentiation, thus influencing tumorigenesis. However, the specific roles of E2Fs in lung adenocarcinoma (LUAD) remain unclear. Data from The Cancer Genome Atlas (TCGA) were used. R version. 4.0.3 and multiple databases (TIMER, cBioportal, gene expression profile interaction analysis [GEPIA], LinkedOmics, and CancerSEA) were utilized to investigate mRNA expression, mutational analysis, prognosis, clinical correlations, co-expressed gene, pathway and network, and single-cell analyses. Immunohistochemistry (IHC) confirmed that E2F transcription factor 7 (E2F7) correlated with LUAD. Among the E2Fs, E2F7 was identified by constructing a prognostic model most significantly associated with overall survival (OS) in LUAD patients. The univariate and multivariate Cox regression analyses showed that E2F7, p-T stage, and p-TNM stage were closely related to OS and progression-free survival (PFS) (P < .05) in LUAD. E2F 7/8 were also identified as significantly associated with tumor stage in the GEPIA database. Compared with paracancerous tissues, E2F7 was up-regulated in LUAD by IHC, and E2F7 might be positively correlated with larger tumors and higher TNM stages. E2F7 may primarily regulate DNA repair, damage, and cell cycle processes and thus affect LUAD tumorigenesis, invasion, and metastasis by LinkedOmics and CancerSEA. E2F7 serves as a potential prognostic biomarker for LUAD.