Implications of TEAD4 in Metabolic Processes of Gastric Cancer [RNA-Seq]

Gastric cancer (GC) is a prevalent malignancy worldwide, imposing a significant global health burden. Despite the development of various treatment strategies, effective management of GC remains elusive. Consequently, extensive research efforts have been directed towards uncovering the underlying molecular mechanisms of GC pathogenesis to develop novel and targeted therapeutic approaches. Among the identified signaling pathways, the Hippo pathway has emerged as a critical contributor to tumor development and acquired drug resistance in GC. It also interacts with multiple other pathways implicated in GC progression. Recent studies have highlighted the role of abnormal DNA methylation patterns in the early stages of GC development, rather than being confined to advanced stages. Specifically, the Hippo pathway member TEAD4 which is implicated in all four GC molecular subtypes, as classified by The Cancer Genome Atlas (TCGA) project, has been found to be hypomethylated in GC. In our research, we employed targeted hypermethylation using a combination of KRAB and DNMT3AL EpiEffectors to achieve epigenetic silencing of the TEAD4 promoter. Post-intervention, consistent with previous studies, we observed a reduction in the cancerous properties of the manipulated GC cells, such as proliferation, colony formation ability, migration, and invasion. Interestingly, transcriptomics results suggest that TEAD4 suppression may imply the downregulation of several carbohydrate-related metabolic pathways, DNA replication and repair mechanisms, as well as carbon metabolism. These findings may offer deeper insights into the multifaceted roles of TEAD4 in the progression of GC.