KAT6A Promotes Lung Cancer Proliferation and Invasion via Keap1-Nrf2 Signaling.
Ning Qian, Bai Weichao, Li Hong, Xue Jing, Li Dan, Chen Tianjun
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.
Key Findings
- KAT6A overexpression promotes lung cancer cell proliferation and invasion.
- KAT6A decreases Keap1 protein expression and enhances Nrf2 signaling activity.
- KAT6A interacts with Nrf2 and increases its transcriptional activity on the heme oxygenase-1 promoter.
- Silencing Nrf2 reverses the proliferative effects of KAT6A.
- High KAT6A expression correlates with advanced tumor stage and shorter overall survival in lung adenocarcinoma patients.
Clinical Significance
KAT6A may serve as a prognostic biomarker and potential therapeutic target in lung adenocarcinoma by modulating the Keap1-Nrf2 oxidative stress pathway and promoting tumor progression.
Citation
Ning Qian, Bai Weichao, Li Honget al.. KAT6A Promotes Lung Cancer Proliferation and Invasion via Keap1-Nrf2 Signaling. Advanced biology. 2026-May.