FXR1 Promotes Esophageal Squamous Cell Carcinoma via JAK2/STAT3/B7-H3 Pathway

Abstract

Background/Aim: Esophageal squamous cell carcinoma (ESCC) is aggressive and has a poor prognosis. RNA-binding protein FXR1 contributes to tumor progression, but its role and mechanism in ESCC remain largely unclear. This study aimed to explore the expression, prognostic value, and molecular mechanism of FXR1 in ESCC. Materials and Methods: FXR1 expression was detected in 115 ESCC tissues and paired normal tissues. Prognostic value was analyzed using Kaplan-Meier and Cox regression. Functional experiments were performed in ESCC cell lines and xenograft models. The mechanism was verified by RNA sequencing, RNA-binding protein immunoprecipitation, RNA pull-down, and Western blotting. Results: FXR1 was significantly upregulated in ESCC and correlated with distant metastasis and poor overall survival. FXR1 promoted cell migration and invasion in vitro, and knockdown suppressed tumor growth in vivo. Mechanistically, FXR1 stabilized JAK2 mRNA, activated JAK2/STAT3 signaling, and upregulated B7-H3 expression. FXR1 expression was positively associated with B7-H3 and inversely correlated with CD8+ T-cell infiltration. Conclusion: FXR1 facilitates ESCC malignant progression and immune evasion, partially through the JAK2/STAT3/B7-H3 regulatory cascade; additional JAK2-independent pathways also contribute to B7-H3 modulation. FXR1 may act as a prognostic biomarker and promising therapeutic candidate for ESCC treatment.