MACC1 expression in colorectal cancer is upregulated by loss of epigenetic repression under oxidative stress condition

Tools

Item Type:	Article
Title:	MACC1 expression in colorectal cancer is upregulated by loss of epigenetic repression under oxidative stress condition
Creators Name:	Phoyen, Suchittra, Dahlmann, Mathias, Herrmann, Pia, Boonla, Chanchai and Stein, Ulrike
Abstract:	Reactive oxygen species (ROS) cause oxidative stress and contribute to cancer genesis and progression. Metastasis-associated in colon cancer 1 (MACC1) is a key metastasis-mediating transcription factor in colorectal cancer (CRC). Whether ROS epigenetically regulated MACC1 expression and increased tumor progression in CRC have not been elucidated so far. We applied oxidative stress in two CRC cell lines with differential MACC1 expression (HCT116 and SW480) and analyzed the distribution of the histone marks H3K4me3 (active) and H4K20me3 (repressive), as well as the expression of MACC1. Alteration in cell motility by ROS was assayed with Boyden chambers. Abundance of H4K20me3 on the MACC1 promoter was determined by ChIP-seq. Induced oxidative stress in SW480 and HCT116 cells increased MACC1 mRNA and protein expression and enhanced cell migration. In the low MACC1 expression SW480 cells, oxidative stress resulted in a higher abundance of the active histone mark H3K4me3, and a lower abundance of repressive mark H4K20me3, both overall and specifically on the MACC1 promoter, compared with the medium MACC1 expression HCT116 cells. Analysis of histological abundances of H3K4me3 and H4K20me3 marks in a small panel of human CRC tumors showed an inverse correlation of H4K20me3 with MACC1. Experimentally, inhibition of H4K20me3 formation caused increased MACC1 mRNA expression in HCT116 cells. Conclusions, we reported a potential ROS-mediated epigenetic regulation of MACC1 expression in CRC through altered histone methylation, as our data suggested an initial epigenetic silencing of MACC1, which was later partially reactivated under oxidative stress.
Keywords:	Colorectal Cancer, H4K20me3, MACC1, ROS, Tumor Progression
Source:	Cell Biochemistry & Function
ISSN:	0263-6484
Publisher:	Wiley
Volume:	43
Number:	8
Page Range:	e70107
Date:	August 2025
Official Publication:	https://doi.org/10.1002/cbf.70107
PubMed:	View item in PubMed

Repository Staff Only: item control page