The histone H3 lysine-27 demethylase UTX plays a critical role in colorectal cancer cell proliferation

Abstract

Abstract Background Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) is an H3K27me3 demethylase, a permissive mark associated with active gene transcription. UTX has been linked to various human cancers. Colorectal cancer (CRC) ranks 3rd among the most common cancers worldwide. However, the role of UTX in colorectal cancer has rarely been reported. Methods RT-qPCR, immunoblotting assays (WB), and immunohistochemistry staining were conducted to explore the UTX expression levels in CRC tissues and surrounding normal tissues. CCK-8 assays, colony formation assays, and flow cytometry were also used to determine the potential role of UTX in CRC cell proliferation in vitro. A cell line-derived xenograft model was performed to determine on the role of UTX in HCT116 cell proliferation in vivo. The protein expression levels of UTX, KIF14, AKT, and GAPDH were examined by WB. Results Compared with surrounding normal tissues, UTX was upregulated in CRC tissues. Knockdown of UTX significantly inhibited proliferation and caused G0/G1 cell cycle arrest in CRC cell lines, and overexpression of UTX significantly promoted proliferation in CRC cells. Furthermore, knockdown of UTX significantly inhibited tumour growth in vivo. In addition, knockdown of UTX decreased the expression of KIF14 and pAKT and increased the expression of P21. Conclusions Our findings indicate that knockdown of UTX inhibits CRC cell proliferation and causes G0/G1 cell cycle arrest through downregulating expression of KIF 14 and pAKT. Thus, UTX may serve as a novel biomarker in CRC.

Keywords

• UTX
• CRC
• Proliferation
• KIF14
• AKT