TCF19 promotes gastric cancer progression through MCM6.

BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide with limited therapeutic options. Identifying molecular drivers of GC progression is crucial for developing effective strategies. Transcription Factor 19 (TCF19), a hub gene implicated in various cancers, has not been well reported in GC. Understanding the role of TCF19 in GC could provide novel insights into tumorigenesis and identify potential therapeutic targets. METHODS: TCF19 expression was analyzed using data from The Cancer Genome Atlas (TCGA), a cohort of 35 GC patients, and 3 GC cell lines (AGS, HGC-27 and MKN45). To investigate the roles of TCF19, gene knockdown and overexpression were performed using TCF19-targeted siRNAs and TCF19-encoding plasmids, respectively. Additionally, the roles of TCF19 in GC growth were examined in vivo. Gene expression profiles were obtained through RNA sequencing in control and TCF19-deficient HGC-27 cells to identify the potential downstream targets. RESULTS: Analysis of the TCGA cohort revealed that TCF19 expression is significantly elevated in GC tissues. This finding was further validated by immunohistochemistry in 35 clinical GC specimens. In vitro experiments showed that TCF19 expression was elevated in 3 GC cell lines, compared to immortal gastric epithelial GES-1 cells. Silencing TCF19 significantly inhibited cell proliferation and migration. Conversely, overexpression of TCF19 produced the opposite effects. In vivo assays in nude mice revealed that TCF19 knockdown markedly reduced the growth of xenografted AGS cells. Additionally, transcriptomic analysis of TCF19-expressing and TCF19-depleted GC cells identified MCM6 as one of the top co-regulated genes. Rescue experiments, in which TCF19 was knocked down while MCM6 was simultaneously overexpressed, provided strong evidence for the pivotal oncogenic role of the TCF19-MCM6 axis in GC. CLINICAL TRIAL NUMBER: Not applicable. CONCLUSION: TCF19 promotes GC progression via regulating MCM6, and the TCF19-MCM6 axis is the potential biomarkers and therapeutic targets for GC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-025-04531-5.