Open Access1,25(OH)2D3 Attenuates IL-1β-Induced Epithelial-to-Mesenchymal Transition Through Inhibiting the Expression of lncTCF7
Author(s) -
Tengyu Li,
Jing Zhu,
Shuai Zuo,
Shanwen Chen,
Jieyi Ma,
Yue Ma,
Shuqin Guo,
Pengyuan Wang,
Yucun Liu
Publication year - 2019
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504018x15360541345000
Subject(s) - calcitriol receptor , chromatin immunoprecipitation , western blot , epithelial–mesenchymal transition , vimentin , cancer research , biology , microbiology and biotechnology , cell growth , vitamin d and neurology , gene expression , downregulation and upregulation , promoter , immunology , endocrinology , immunohistochemistry , biochemistry , gene
The activated form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], regulates numerous cellular processes, including inhibition of cancer progression. IL-1β 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-1β 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-1β. 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-1β-induced increased proliferation and invasion in colorectal cancer through enhancing VDR, which inhibits the expression of lncTCF7 by directly binding to its promoter region.