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TIM-1 inhibits cancer cell proliferation by regulating IFIT2 and is correlated with prognosis in bladder cancer

ABSTRACT: Bladder cancer (BC) is one of the most common cancers in the world. T-cell immunoglobulin and mucin domain 1 (TIM-1) are involved in the progression of multiple tumors. However the role of TIM-1 in BC progression is poorly understood. In this 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 inhibits 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 TIM-1 overexpression. Mechanistically, our data revealed that TIM-1 promotes IFN-α release and activates 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 hinders the tumor suppressive effect of TIM-1. Our results revealed that TIM-1 is a potential molecular marker for BC prognosis and indicate that high TIM-1 expression suppresses BC cell proliferation in an IFIT2/p-STAT1-dependent manner.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226545 | GEO | 2023/03/08

REPOSITORIES: GEO

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IFIT2 mediates IFN signaling

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