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

• Published in: Oncology research Vol. 27; no. 7; pp. 739 - 750
• Main Authors: Li, Tengyu, Zhu, Jing, Zuo, Shuai, Chen, Shanwen, Ma, Ju, Ma, Yongchen, Guo, Shihao, Wang, Pengyuan, Liu, Yucun
• Format: Journal Article
• Language: English
• Published: Elmsford, NY Cognizant Communication Corporation 12.07.2019
• Subjects: 1,25(oh)2d3; Animals; Cell Proliferation; Epithelial-Mesenchymal Transition; Epithelial-Mesenchymal Transition (emt); Hepatocyte Nuclear Factor 1-alpha - metabolism; Humans; Il-1β; Interleukin-1beta - metabolism; Lnctcf7; Male; Mice; Mice, Nude; Vitamin D - analogs & derivatives; Vitamin D - pharmacology; Vitamin D - therapeutic use; Vitamin D Receptor
• ISSN: 0965-0407; 1555-3906
• DOI: 10.3727/096504018X15360541345000

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.