H19 Overexpression Induces Resistance to 1,25(OH)2D3 by Targeting VDR Through miR-675-5p in Colon Cancer Cells

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2017-03, Vol.19 (3), p.226-236
• Main Authors: Chen, Shanwen, Bu, Dingfang, Ma, Yuanyuan, Zhu, Jing, Chen, Guowei, Sun, Lie, Zuo, Shuai, Li, Tengyu, Pan, Yisheng, Wang, Xin, Liu, Yucun, Wang, Pengyuan
• Format: Article
• Language: English
• Subjects: Animals; Calcitriol - pharmacology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Disease Models, Animal; Drug Resistance - genetics; Gene Expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Regulatory Networks; Humans; Mice; MicroRNAs - genetics; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncology; Original article; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; RNA Interference; RNA, Long Noncoding - genetics; Signal Transduction - drug effects; Xenograft Model Antitumor Assays
• ISSN: 1476-5586; 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2016.10.007

Abstract The long noncoding (lnc) RNA H19 was involved in the tumorigenesis of many types of cancer. However, the role of H19 in the tumorigenesis of colon cancer has not been fully illustrated. Recent studies suggested a potential relationship between H19 and vitamin D receptor (VDR) signaling. Considering the pivotal role of VDR signaling in the colon epithelium both physiologically and pathologically, the correlation between H19 and VDR signaling may have an important role in the development of colon cancer. In this study, the correlation between H19 and vitamin D receptor (VDR) signaling and the underlying mechanisms in colon cancer were investigated both in vitro and in vivo . The results suggested that VDR signaling was able to inhibit the expression of H19 through regulating C-Myc/Mad-1 network. H19, on the other hand, was able to inhibit the expression of VDR through micro RNA 675-5p ( miR-675-5p ). Furthermore, H19 overexpression induced resistance to the treatment with 1,25(OH)2D3 both in vitro and in vivo . Together, these results suggested that H19 overexpression might be one of the mechanisms underlying the development of resistance to the treatment with 1,25(OH)2D3 in the advanced stage of colon cancer.