Abstract
Abstract Bladder cancer is the fourth most common cancer diagnosed and eighth leading cause of cancer death in men. Metastasis is the primary reason for mortality. The 5-year survival rates for localized and metastatic bladder cancers are 94% and 6%, respectively. Therefore, more effective strategies to prevent and inhibit bladder cancer invasion and metastasis are needed to prolong survival. Epidemiological and experimental studies support a role for 1,25(OH) 2D3 (1,25D3) in cancer prevention and treatment. More recently, 1,25D3 has also been reported to inhibit tumor cell invasion and metastasis in several model systems. To study the anti-tumor effect of 1,25D3 in bladder cancer, we selected four human bladder cell lines including T24, 253J, 253J-BV and TCC-SUP cells. 253J-BV is a metastatic line generated from 253J cells through a series of orthotopic inoculation. Vitamin D receptor was expressed and induced by 1,25D3 in all four cell lines. However, treatment with 1,25D3 did not significantly affect the proliferation of the bladder cancer cell lines. To investigate the impact of 1,25D3 on bladder cancer cell migration and invasion, the cells were treated with control EtOH or 1,25D3 in the wound healing assay or chamber-based migration or invasion assays. 1,25D3 suppressed migration and invasion of 253J-BV and TCC-SUP cells but neither 253J nor T24 cells. MiRNAs play critical regulatory roles in cancer cell migration and invasion. We selected 253J and 253J-BV cells for further investigation of the role of miRNAs in 1,25D3 regulation of migration and invasion. Our previous PCR panel studies showed that 1,25D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells. From the markedly regulated miRNAs, we chose miR-101-3p and miR-126-3p to examine their potential contribution to the inhibition of migration and invasion by 1,25D3. 1,25D3 induced the expression of miR-101-3p and reduced miR-126-3p expression in 253J-BV cells but not 253J cells. To investigate the role of the two miRNAs, we employed pre-miR and miRNA inhibitors. Transfection with miR-101-3p inhibitor vector suppressed migration and invasion in 253J-BV cells. In addition, miR-101-3p inhibitor rescued 1,25D3-induced inhibition of migration and invasion in 253J-BV cells. On the other hand, pre-miR-101-3p transfection followed by 1,25D3 treatment resulted in further reduction of migration and invasion in 253J-BV cells. However, transfection with miR-126-3p inhibitor or pre-miR-126-3p did not alter 1,25D3-inhibition of migration and invasion in 253J-BV cells. These results indicate that 1,25D3 suppresses migration and invasion through the induction of miR-101-3p in human bladder cancer 253J-BV cells. Citation Format: Yingyu Ma, Wei Luo, Rachel Pratt, Donald L. Trump, Candace S. Johnson. 1,25D3 inhibits migration and invasion through miR-101-3p in human bladder cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5095. doi:10.1158/1538-7445.AM2015-5095
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