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 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 garbage pail kids 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 tumor stage and poor overall survival of patients.
Moreover, miR-153 expression inhibited bladder cancer cell growth DAILY FACE WASH 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.