RNF19A facilitates gastric cancer progression by regulating the Hippo/YAP axis.

BACKGROUND: RNF19A is a poorly characterized ring between ring finger (RBR) E3 ubiquitin ligase that acts as a tumor suppressor in bladder cancer, whereas as an oncogene in non-small cell lung cancer. However, the biological functions of RNF19A in gastric cancer cells and whether RNF19A targets other substrates involved in gastric cancer progression remain unclear. Here, we report that RNF19A expression is elevated in gastric cancer tissues and is indicative of poor prognoses.

METHODS: Microarray gastric cancer tissue sections were subjected to immunohistochemistry (IHC). The effects of RNF19A under-or over-expression in gastric cancer cells were evaluated by in vitro cell proliferation, migration, invasion, and apoptosis assays. In vivo xenograft and metastasis models generated from RNF19A under - expressing gastric cancer cells were used to determine the role of RNF19A in gastric cancer tumor growth and metastasis. The specific mechanism of RNF19A in gastric cancer cells was studied using western blotting, nuclear and cytoplasmic protein isolation, immunofluorescence (IF), co-immunoprecipitation, protein half-life and in vivo ubiquitylation assay.

RESULTS: In vitro and in vivo experiments showed that RNF19A, serving as an oncogene, enhanced the growth and metastasis of gastric cancer cells. RNF19A inhibited the Hippo/yes-associated protein (YAP) pathway by reducing YAP phosphorylation and increasing nuclear YAP levels. At the molecular level, RNF19A interacted with and induced the K48-linked ubiquitination of Ste20-like serine/threonine kinase1 (MST1), which led to MST1 degradation. The knockdown of MST1 partially reversed the suppression of gastric cancer cell proliferation, migration, and invasion induced by RNF19A knockdown.

CONCLUSION: RNF19A，disrupting the Hippo/YAP axis, which may serve as a diagnostic biomarker and potential therapeutic target for gastric cancer.