# NAT10-mediated ac4C RNA acetylation stabilizes CXCL5/DEK mRNA to drive proliferation and metastasis in lung adenocarcinoma

## TL;DR

This study shows that NAT10, an RNA acetylation enzyme, promotes lung cancer growth and spread by stabilizing specific mRNAs.

## Contribution

The study identifies NAT10 as a novel driver of lung adenocarcinoma progression through ac4C RNA modification.

## Key findings

- NAT10 is significantly upregulated in lung adenocarcinoma tissues and cell lines.
- NAT10 acetylates CXCL5 and DEK mRNAs, preventing their degradation and promoting cancer progression.
- Targeting NAT10 reduces tumor growth and metastasis in mouse models.

## Abstract

Investigating the epigenetic mechanisms underlying lung adenocarcinoma (LUAD) through the lens of N4-acetylcytosine (ac4C) modification could innovate cancer treatment strategies and targets. We used biological information methods to analyze shared data, with a focus on studying N-acetyltransferase 10 (NAT10), which is the only known ac4C “writer” protein. Our analysis revealed a significant upregulation of NAT10 expression in LUAD, a finding that was corroborated by investigations in both LUAD cancer tissue samples and cell lines. Subsequently, we employed CRISPR/Cas9 technology to knock out the NAT10 gene and analyzed the resulting knockout cells using acRIP-seq and RNA-seq techniques. Our findings demonstrated different expressions of the genes C-X-C motif chemokine ligand 5 (CXCL5) and DEK proto-oncogene (DEK), and functional enrichment analysis indicated a strong association with the adhesion signaling pathway. Laboratory experiments revealed that NAT10 acts as an ac4C “writer,” promoting the acetylation of CXCL5 and DEK and thus preventing the degradation of their mRNAs. Moreover, NAT10 was found to significantly affect the number of metastases and tumor growth following the injection of cancer cells into the tail vein of mice. Our research data suggests that targeting NAT10 has the potential to serve as a diagnostic biomarker or prognostic target for developing anti-metastatic therapies aimed at disrupting the adhesion process.