Lysine acetyltransferase KAT2A modulates ferroptosis during colorectal cancer development

Abstract

Background

Histone modifications, especially the lysine acetylation, have drawn increasing attention in cancer research area. The aim of this research is to explore the molecular mechanisms underlying the regulation of lysine acetyltransferase 2 A (KAT2A) on colorectal cancer (CRC).

Methods

Clinical samples were collected from patients with CRC. The expression and correlation between KAT2A and ferroptosis suppressor SLC7A11 and glutathione peroxidase 4 (GPX4) were measured by qPCR and Pearson correlation analysis. NCP cells were transfected with KAT2A overexpression vectors or siRNAs. The proliferation of cells was measured by CCK-8 and colony formation assay. Cell migration and invasion was analyzed by Transwell. The accumulation of lipid peroxidation, ferrous iron, and malondialdehyde (MDA) were analyzed to determine cell ferroptosis. The expression of cell metastasis biomarkers was measured by western blotting assay. Interaction between KAT2A with GPX4 gene was measured by chromatin immunoprecipitation (ChIP).

Results

The KAT2A, GPX4, and SLC7A11 expression was notably elevated in tumor tissues compared with the paired non-tumor tissues from CRC patients. The expression of KAT2A showed positive correlation with GPX4 and SLC7A11. Overexpression of KAT2A recovered the cell proliferation, migration, and invasion of CRC cells that suppressed by ferroptosis inducer erastin, along with deceased levels of ROS, iron, Fe2+, and MDA. Overexpression of KAT2A suppressed E-cadherin level and increased N-cadherin, Snail, and Vimentin expression in CRC cells. KAT2A interacted with GPX4 promoter region.

Conclusions

In conclusion, our findings demonstrated that KAT2A modulates the histone acetylation of GPX4 to regulate proliferation, metastasis, and ferroptosis of CRC cells.

Keywords:

• Colorectal cancer
• lysine acetyltransferase 2A
• ferroptosis
• glutathione peroxidase 4

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.