Motile sperm domain containing 1 is upregulated by the Wnt/β-catenin signaling pathway in colorectal cancer

结直肠癌中 Wnt/β-catenin 信号通路上调含有 1 的运动精子结构域

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作者:Chiaki Horie, Chi Zhu, Kiyoshi Yamaguchi, Saya Nakagawa, Yumiko Isobe, Kiyoko Takane, Tsuneo Ikenoue, Yasunori Ohta, Yukihisa Tanaka, Susumu Aikou, Giichiro Tsurita, Yuka Ahiko, Dai Shida, Yoichi Furukawa

Abstract

Aberrant activation of the Wnt/β-catenin signaling pathway plays a crucial role in the development and progression of colorectal cancer. Previously, we identified a set of candidate genes that were regulated by this signaling pathway, and the present study focused on motile sperm domain containing 1 (MOSPD1). Immunohistochemical staining revealed that the expression of MOSPD1 was elevated in tumor cells from colorectal cancer tissues compared with in non-tumor cells. Using ChIP-seq data and the JASPAR database, the regulatory region(s) in the MOSPD1 gene as a target of the Wnt/β-catenin signaling pathway were searched, and a region containing three putative TCF-binding motifs in the 3'-flanking region was identified. Additional analyses using reporter assay and ChIP-quantitative PCR suggested that this region harbors enhancer activity through an interaction with transcription factor 7 like 2 (TCF7L2) and β-catenin. In addition, chromatin conformation capture assay revealed that the 3'-flanking region interacts with the MOSPD1 promoter. These data suggested that MOSPD1 was regulated by the β-catenin/TCF7L2 complex through the enhancer element located in the 3'-flanking region. These findings may be helpful for future studies regarding the precise regulatory mechanisms of MOSPD1.

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