MicroRNA-153 Decreases Tryptophan Catabolism and Inhibits Angiogenesis in Bladder Cancer by Targeting Indoleamine 2,3-Dioxygenase 1
MicroRNA-153 Decreases Tryptophan Catabolism and Inhibits Angiogenesis in Bladder Cancer by Targeting Indoleamine 2,3-Dioxygenase 1
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Background: Metastasis is the primary cause of cancer deaths, warranting further investigation.This study assessed microRNA-153 (miR-153) expression in icon track bar f250 bladder cancer tissues and investigated the underlying molecular mechanism of miR-153-mediated regulation of bladder cancer cells.Methods: Paired tissue specimens from 45 bladder cancer patients were collected for qRT-PCR.The Cancer Genome Atlas (TCGA) dataset was used to identify associations of miR-153 with bladder cancer prognosis.Bladder cancer tissues and immortalized cell lines were used for the following experiments: miR-153 mimics and indoleamine 2,3-dioxygenase 1 (IDO1) siRNA transfection; Western blot, cell viability, colony formation, and Transwell analyses; nude mouse xenograft; and chicken embryo chorioallantoic membrane angiogenesis (CAM) assays.
Human umbilical vein endothelial cells (HUVECs) were co-cultured with bladder cancer cells for the tube formation assay.The luciferase reporter assay was used to confirm miR-153-targeting genes.Results: miR-153 expression was downregulated in bladder cancer tissues and cell lines, and reduced miR-153 expression was associated with advanced honeywell pa404a1009 tumor stage and poor overall survival of patients.Moreover, miR-153 expression inhibited bladder cancer cell growth by promoting tumor cell apoptosis, migration, invasion, and endothelial mesenchymal transition (EMT) in vitro and tumor xenograft growth in vivo, while miR-153 expression suppressed HUVEC and CAM angiogenesis.At the gene level, miR-153 targeted IDO1 expression and inhibited bladder cancer cell tryptophan metabolism through inhibiting IL6/STAT3/VEGF signaling.
Conclusions: Collectively, our data demonstrate that miR-153 exerts anti-tumor activity in bladder cancer by targeting IDO1 expression.Future studies will investigate miR-153 as a novel therapeutic target for bladder cancer patients.