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

• Published in: Oncology letters 2022-08, Vol.24 (2), Article 282
• Main Authors: Horie, Chiaki, Zhu, Chi, Yamaguchi, Kiyoshi, Nakagawa, Saya, Isobe, Yumiko, Takane, Kiyoko, Ikenoue, Tsuneo, Ohta, Yasunori, Tanaka, Yukihisa, Aikou, Susumu, Tsurita, Giichiro, Ahiko, Yuka, Shida, Dai, Furukawa, Yoichi
• Format: Article
• Language: English
• Subjects: Antibodies; Binding sites; Cell cycle; Cell growth; Colorectal cancer; Gene expression; Genomics; Mutagenesis; Mutation; Oncology; Plasmids; Proteins; Sperm; Statistical analysis; Tumors
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2022.13402

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.