Probing the metabolic regulator and candidate tumor suppressor ALDH1L1 as a target for non-small cell lung cancer gene therapy.

ABSTRACT: ALDH1L1, a major cytosolic folate enzyme and key regulator of one-carbon metabolism, is strongly and ubiquitously downregulated in lung adenocarcinomas (LUADs) and silenced in LUAD cell lines. Analysis of publicly available databases indicates that ALDH1L1 expression is associated with better prognosis and overall survival in LUAD patients. Here we used lentiviral delivery of ALDH1L1 to target metabolism in ALDH1L1-deficient LUAD cell lines A549 and H460. In these cells, ALDH1L1 expression led to strong inhibition of proliferation, colony formation, and migration. Untargeted metabolomic analysis has shown that ALDH1L1 knockin produces a strong effect on the metabotype of A549 cells including alterations in the tricarboxylic acid cycle intermediates and acylcarnitines, indicative of the imp

SUBMITTER: Abdellatef AA 

PROVIDER: S-EPMC12450569 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature