Discovery of Small Molecules That Inhibit MYC mRNA Translation Through hnRNPK and Induction of Stress Granule-Mediated mRNA Relocalization.

ABSTRACT: MYC is a key oncogenic driver frequently overexpressed in non-small cell lung carcinoma (NSCLC) and other cancers, where its protein levels often exceed what would be expected from MYC mRNA levels alone, suggesting post-transcriptional regulation. Strategies to inhibit MYC function by targeting mRNA translation hold potential for therapeutics utility in Myc-dependent cancers. We developed TranslationLight, a high-content imaging platform which detects MYC mRNA translation in human cells. Using this system, we conducted a high-throughput screen of ~100,000 compounds to identify small molecules that selectively modulate MYC translation. Candidate compounds were evaluated by immunofluorescence, ribosome profiling, RNA sequencing, cellular thermal shift assay

SUBMITTER: Sheinberger Y 

PROVIDER: S-EPMC12427919 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature