KHDRBS3-mediated upregulation of circ_0024107 in gastric cancer cells and GC-MSCs synergistically drives gastric cancer cell migration and invasion.

Abstract

Gastric cancer is a significant global health concern due to its high morbidity and mortality. Gastric cancer-associated mesenchymal stem cells (GC-MSCs) significantly contribute to its progression, with circ_0024107 being notably elevated in these cells and essential for their tumor-promoting activities. However, the expression and function of this circRNA in gastric cancer cells as well as its upstream regulators remain unclear. qPCR was used to assess circ_0024107 expression levels. Gain- and loss-of-function experiments evaluated its roles. Transwell assays measured cell migration and invasion. KHDRBS3 was predicted and validated through database analysis and qPCR, and its effects on circ_0024107 were analyzed using qPCR and transwell assays. The expression and clinical implications of KHDRBS3 in gastric cancer were evaluated using the TCGA-STAD database. circ_0024107 expression was elevated in gastric cancer cells, where it promotes migration and invasion. GC-MSCs further enhanced these capabilities by upregulating circ_0024107. KHDRBS3 was identified and validated as a regulator of circ_0024107 expression in both gastric cancer cells and GC-MSCs. Knocking down KHDRBS3 significantly reduced circ_0024107 levels, hindering gastric cancer cell migration and invasion, and weakening the influence of GC-MSCs on tumor cells. KHDRBS3 was abnormally elevated in gastric cancer tissues and correlated with patients' poor prognosis. KHDRBS3-mediated upregulation of circ_0024107 in gastric cancer cells and GC-MSCs synergistically enhances gastric cancer progression. This elucidates novel molecular interactions between GC-MSCs and gastric cancer cells, thereby presenting a promising therapeutic target for effectively mitigating gastric cancer metastasis.