Troponin C-1 Activated by E2F1 Accelerates Gastric Cancer Progression via Regulating TGF-β/Smad Signaling

Abstract

Background Troponin C-1 (TNNC1) has been previously characterized as an oncogenic gene. Aims This study aimed to reveal the roles of TNNC1 in gastric cancer and the potential underlying mechanisms. Methods TNNC1 siRNAs and TNNC1 overexpression plasmid were used to alter its expression in AGS, MKN45, and HGC-27 cells. CCK-8 assay, colony formation, EdU assay, flow cytometry, transwell assay, and scratch test were conducted to measure the phenotype changes. In vivo effects of TNNC1 silence were confirmed by using a xenograft mouse model. Bioinformatics analysis was conducted to screen out the transcription factor and downstream signaling of TNNC1. Results TNNC1 was highly expressed in gastric cancer tissues and cell lines, and its expression was associated with poor prognosis. TNNC1 silence suppressed the proliferation, migration, and invasion of AGS and MKN45 cells. However, TNNC1 silence induced apoptosis by mediating the cleavage of caspase-3 and caspase-9. Overexpression of TNNC1 in HGC-27 cells led to the contrary effects. The anti-tumor effects of TNNC1 silence were also confirmed in a xenograft animal model. E2F1 was validated as an upstream transcription factor of TNNC1. Effects of TNNC1 silence on AGS cell migration and invasion were attenuated by E2F1 overexpression. Besides, TGF-β/Smad was a downstream signaling pathway of TNNC1. The anti-tumor impacts of TNNC1 silence were weaken by SB431542 (a specific inhibitor of TGF-β signaling) while accelerated by TGF-β. Conclusion TNNC1 activated by E2F1 functioned as an oncogenic gene through regulating TGF-β/Smad signaling. TNNC1 was suggested as a potential molecular drug target of gastric cancer.

Drug-likeness evaluation and inhibitory mechanism of emodin derivative on cardiac fibrosis based on MTA3 pathway

“…These ndings suggest E2F1 as a potential therapeutic target for mitigating brosis and preserving cardiac function in cardiovascular diseases. Furthermore, E2F1 interacts with other brosisrelated pathways like TGF-β/Smad (Fang et al, 2022), highlighting its central role in brosis progression and the need for comprehensive anti-brotic therapies.…”

Downregulation of Tumor Promotor Genes in Oryza Sativa Linn.-Induced Antiproliferative Activity of Human Squamous Carcinoma Cells

“…Our results found downregulation of the gene, which was in line with our findings of antiproliferative activity. There is also evidence in the literature of interaction between Smad3 and members of the E2F family through signaling via the microRNA, miR-618, in head and neck squamous cell carcinoma (HNSCC) (Hui et al, 2016), and through troponin C-1 in gastric cancer (Fang et al, 2022). Smad3 is highly associated with TGF-β signaling (Derynck and Zhang, 2003) and when downregulated, is associated with higher patient survival rate in HNSCC (Xie et al, 2013).…”