CDC40 suppression induces CDCA5 splicing defects and anti-proliferative effects in lung cancer cells.

ABSTRACT: High mortality and low response rates in lung cancer patients call for novel therapeutic targets. Data mining of whole-genome genetic dependency screens suggest Cell Division Cycle 40 (CDC40) to be an essential protein for lung cancer cell survival. We characterized CDC40 knockdown effects in multiple lung cancer cell lines, revealing induced cell cycle defects that resulted in strong growth inhibition and activation of apoptosis. Global transcriptional and splicing changes were also investigated, where CDC40 knockdown resulted in perturbation of splicing- and translation-related genes as well as more transcripts with intron retention. In the transcript of the cell cycle regulatory protein CDCA5, CDC40 knockdown was shown to induce retention of the first intron, leading to an increase in t

SUBMITTER: Hu D 

PROVIDER: S-EPMC11696760 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature