Open Access

ARTICLE

1,25(OH)2D3 Attenuates IL-1b-Induced Epithelial-to-Mesenchymal Transition Through Inhibiting the Expression of lncTCF7

Tengyu Li, Jing Zhu, Shuai Zuo, Shanwen Chen, Ju Ma, Yongchen Ma, Shihao Guo, Pengyuan Wang, Yucun Liu

Department of General Surgery, Peking University First Hospital, Peking University, Beijing, P.R. China

Oncology Research 2019, 27(7), 739-750. https://doi.org/10.3727/096504018X15360541345000

Abstract

The activated form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], regulates numerous cellular processes, including inhibition of cancer progression. IL-1 has been reported to facilitate cancer development, especially by inducing an epithelial-to-mesenchymal transition (EMT) in several malignant tumors. However, the underlying mechanism of 1,25(OH)2D3 and IL-1 in colorectal cancer (CRC) still remains largely unknown. To fill in this knowledge gap, we measured cell proliferation and invasion by CCK-8 and Transwell assays after stimulation with 1,25(OH)2D3 and IL-1 . E-cadherin and vimentin were chosen as markers of EMT measured by immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blot. The expression and function of the vitamin D receptor (VDR) was evaluated by Western blot and luciferase reporter assay. qRT-PCR and RNA-FISH were performed to detect the expression and location of lncTCF7 in vitro. The binding sites of VDR in the lncTCF7 promoter were confirmed by a chromatin immunoprecipitation assay. Based on the above experiments, we found that 1,25(OH)2D3 attenuates IL-1 - induced increased proliferation and invasion in colorectal cancer through enhancing VDR, which inhibits the expression of lncTCF7 by directly binding to its promoter region.

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