Open Access

ARTICLE

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

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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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