FoxM1 promotes the proliferation of cervical adenocarcinoma cells through transcriptional activation of FAM83D

Abstract

Cervical adenocarcinoma exhibits a steadily increasing global incidence with notable demographic shifts toward younger populations. Despite the absence of distinct clinical guidelines differentiating its management from squamous cell carcinoma, treatment strategies remain non-specific, contributing to suboptimal patient outcomes. To address this therapeutic gap, we systematically investigated molecular disparities between adenocarcinoma and squamous cell carcinoma through integrated ChIP-seq and RNA-seq analyses. Our multi-omics approach identified FAM83D as a novel transcriptional target directly regulated by the FoxM1 oncoprotein, demonstrating adenocarcinoma-specific expression in HeLa cells. This regulatory relationship was experimentally validated using quantitative PCR and luciferase reporter assays. Mechanistically, we delineated that FoxM1 governs cell cycle progression and proliferation via FAM83D-dependent pathways. Intriguingly, co-immunoprecipitation studies revealed a physical interaction between FoxM1 and karyopherin α2 (KPNA2), another adenocarcinoma-enriched protein, with their expression levels showing significant positive correlation in clinical specimens. This study not only elucidates the oncogenic axis of FoxM1-FAM83D but also reveals the dual regulatory role of FoxM1 as both a transcriptional activator and protein interaction hub in cervical adenocarcinoma pathogenesis. These findings expand the molecular landscape of this malignancy and identify potential therapeutic entry points for targeted adenocarcinoma interventions.