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

Xin Tang,G Sun,Ping Hu,Chaoting Chen,Yi Chen,Xiaomin Lv,Yun Sun,Yu Wang,Caofeng Wang,Ping Lu,Wenwei Cai,Jing Cheng,Shaojun Ma,Jing Sheng

doi:10.1186/s12935-019-0841-y

Abstract

BackgroundUbiquitously 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.MethodsRT-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.ResultsCompared 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.ConclusionsOur 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.

Highlights

Transcribed tetratricopeptide repeat, X chromosome (UTX) is an H3K27me3 demethylase, a permissive mark associated with active gene transcription
Correlation studies indicated that the expression level of UTX in patients with Colorectal cancer (CRC) was proportional to the stage of disease progression (Fig. 1b)
We found that the RNA and protein levels of UTX in colorectal cancer cell lines were significantly higher than those of the normal colorectal NCM460 cells (Fig. 1d, e)

Summary

Introduction

Transcribed tetratricopeptide repeat, X chromosome (UTX) is an H3K27me demethylase, a permissive mark associated with active gene transcription. Colorectal cancer (CRC) ranks 3rd among the most common cancers worldwide. The role of UTX in colorectal cancer has rarely been reported. Tang et al Cancer Cell Int (2019) 19:144 can enhance the proliferation of breast cancer cells [9], it remains unclear whether and how UTX influences the development of CRC. KIF14 expression was shown to promote the proliferation of colorectal cancer cells. The expression level of KIF14 has been reported to be increased in many tumour types, such as glioma, lung cancer, hepatocellular carcinoma, ovarian cancer, breast cancer, and laryngeal carcinoma [17,18,19,20,21,22,23], compared to normal tissues. KIF14 was found to promote cell proliferation via the activation of AKT in colorectal cancer [24]

Objectives

Methods

Results

Discussion

Conclusion