Upregulation of SLC25A1 by MAZ reprograms fatty acid synthesis and fuels LUAD malignancy.

Abstract

Lung adenocarcinoma (LUAD) is a type of lung cancer with high incidence and mortality rates. Zinc finger protein 801 (MAZ) regulates cellular growth, proliferation, and differentiation, and its abnormal expression is associated with the occurrence of various tumors. In this study, the objective is to investigate the impact and underlying mechanism of MAZ on the malignant progression of LUAD. The expression of solute carrier family 25 member 1 (SLC25A1) was found to be elevated in LUAD, which indicated a relationship with a negative prognosis. Within LUAD cells, SLC25A1 was observed to not only boost proliferation but also hinder apoptosis and further augment fatty acid synthesis. MAZ, which was identified as the upstream regulator of SLC25A1, was also overexpressed in LUAD, thereby positively regulating the expression of SLC25A1. In addition, MAZ was found to accelerate the malignant behaviors of LUAD cells, specifically through its regulation of SLC25A1. Furthermore, in vivo studies confirmed that MAZ stimulated the malignant progression of LUAD via its influence on SLC25A1. In conclusions, MAZ mediates the upregulation of SLC25A1, which modifies the fatty acid synthesis pathway and fuels the malignant progression of LUAD. These findings suggest a new strategy for the targeting therapy in LUAD patients.