1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells

Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1 alpha,25 (OH)(2)D-3 in cancer prevention and treatment. The antitumor activities of 1 alpha,25(OH)(2)D-3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1 alpha,25(OH)(2)D-3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1 alpha,25(OH)(2)D-3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1 alpha,25(OH)(2)D-3. VDR target gene 24-hydroxylase was induced by 1 alpha,25(OH)(2)D-3 in both cell lines, indicating functional 1 alpha,25(OH)(2)D-3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1 alpha,25(OH)(2)D-3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1 alpha,25(OH)(2)D-3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. (C) 2014 Elsevier Ltd. All rights reserved.