TIM-1 Inhibits Cancer Cell Proliferation by Regulating IFIT2 and is Correlated with Prognosis in Bladder Cancer

Bladder cancer (BC) is one of the most common cancers worldwide. T-cell immunoglobulin and mucin domain 1 (TIM-1) is involved in the progression of multiple tumors. The role of TIM-1 in BC progression is poorly understood. In the present study, we searched the Gene Expression Profiling Interactive Analysis (GEPIA) database and performed immunohistochemistry (IHC) to assess TIM-1 protein expression in bladder cancer (BC) patients. The results demonstrated that BC with high TIM-1 expression was associated with longer overall survival (OS) and disease-specific survival (DSS) than BC with low TIM-1 expression. Overexpression of TIM-1 inhibited BC cell proliferation in both cell culture and animal experiments. RNA sequencing data indicated that interferon-induced protein with tetratricopeptide repeats (IFIT) genes induced by interferon-α (IFN-α) were significantly enriched among the genes upregulated by overexpression of TIM-1. Mechanistically, our data revealed that TIM-1 promoted IFN-α release and activated the IFIT2/p-STAT1 pathway, which is known to be related to tumor cell proliferation. Moreover, knockdown of IFIT2 in TIM-1-overexpressing BC cells hindered the tumor suppressive effect of TIM-1. Our results revealed TIM-1 as a potential molecular marker for prognosis in BC and indicate that high TIM-1 expression suppresses BC cell proliferation in an IFIT2/p-STAT1-dependent manner.