RBMS1 promotes gastric cancer metastasis through autocrine IL-6/JAK2/STAT3 signaling

Abstract

AbstractMetastasis is the most important reason for the poor prognosis of gastric cancer (GC) patients, and the mechanism urgently needs to be clarified. Here, we explored a prognostic model for the estimation of tumor-associated mortality in GC patients and revealed the RNA-binding protein RBMS1 as a candidate promoter gene for GC metastasis by analyzing GOBO and Oncomine high-throughput sequencing datasets for 408 GC patients. Additionally, RBMS1 was observed with overexpression in 85 GC patient clinical specimens by IHC staining and further be verified its role in GC metastasis via inducing EMT process both in in vitro and in vivo experiments. Moreover, we identified that IL-6 was predicted to be one of the most significant upstream cytokines in the RBMS1 overexpression gene set based on the Ingenuity Pathway Analysis (IPA) algorithm. Most importantly, we also revealed that RBMS1 could promote migration and invasion through IL6 transactivation and JAK2/STAT3 downstream signaling pathway activation by influencing histone modification in the promoter regions after binding with the transcription factor MYC in the HGC-27 and SGC-7901 GC cell lines. Hence, we shed light on the potential molecular mechanisms of RBMS1 in the promotion of GC metastasis, which suggests that RBMS1 may be a potential therapeutic target for GC patients.