Work

Arsenic promotes ROS-mediated malignant transformation of bronchial epithelial cells by specifically downregulating TXNL1 expression

Year: 2025

Type: article

Abstract: Arsenic exposure is a known cause of lung cancer, primarily mediated through reactive oxygen species (ROS) generation and oxidative DNA damage. However, the precise mechanism by which arsenic modulates ROS levels remains unclear. This study reveals that, contrary to the upregulation of various key ROS scavenging genes, arsenic specifically downregulates the expression of the redox-active protein thioredoxin-like 1 (TXNL1) both in vitro and in vivo. Enhancing TXNL1 expression significantly suppresses arsenic-induced ROS production, DNA oxidative damage, and malignant transformation. Mechanistic investigations indicate that arsenic downregulates TXNL1 expression through the downregulation of the deubiquitinase USP10, which leads to increased ubiquitination and degradation of TXNL1. Additionally, arsenic promotes hypermethylation of the USP10 promoter region by upregulating the expression of DNA methyltransferase 1 (DNMT1), resulting in transcriptional repression of USP10. In summary, our results reveal that arsenic disrupts redox homeostasis via the DNMT1-USP10-TXNL1 axis, identifying a potential target for preventing arsenic-induced lung carcinogenesis.

Source: Communications Biology

DOI: 10.1038/s42003-025-09216-z