KAT6A Promotes Lung Cancer Proliferation and Invasion via Keap1-Nrf2 Signaling.

Abstract

This study aimed to investigate the role of lysine acetyltransferase 6A (KAT6A) in lung cancer progression and its potential involvement in Nrf2-related oxidative stress regulation. KAT6A was overexpressed or silenced in A549 and H1299 lung cancer cells. KAT6A expression was verified by quantitative reverse transcription polymerase chain reaction and Western blot. Cell Counting Kit-8 and Transwell assays showed that KAT6A overexpression promoted cell proliferation and invasion, whereas KAT6A silencing suppressed cell proliferation. KAT6A overexpression decreased the expression of Keap1 protein and enhanced Nrf2 signaling activity. Oxidative stress evaluation using 2',7'-dichlorodihydrofluorescein diacetate staining, malondialdehyde (MDA) detection, and superoxide dismutase (SOD) activity assays indicated decreased reactive oxygen species levels, reduced MDA content, and elevated SOD activity. Co-immunoprecipitation confirmed the interaction between KAT6A and Nrf2, and dual-luciferase reporter assays showed enhanced Nrf2 transcriptional activity on the heme oxygenase-1 promoter. Silencing Nrf2 reversed the effects of KAT6A on proliferation. Immunohistochemistry of clinical lung adenocarcinoma samples showed that high KAT6A expression correlated with advanced tumor stage and shorter overall survival. These findings suggest that KAT6A regulates oxidative stress via the Keap1-Nrf2 pathway, thereby promoting malignant progression in lung adenocarcinoma, and may serve as a potential prognostic biomarker.