CDCA7 Promotes Proliferation and Suppresses Apoptosis in Gastric Cancer via HELLS-Mediated Chromatin Remodeling

In various tumor types, cell division cycle-associated 7 (CDCA7) is involved in chromatin remodeling and DNA methylation. However, its biological functions and regulatory mechanisms in gastric cancer (GC) remain unknown. This investigation intended to identify the function of CDCA7 in GC progression and elucidate its epigenetic regulatory mechanisms.

Differentially expressed genes (DEGs) were detected from the GSE19826, TCGA-GC, and GSE56807 datasets. Networks of protein-protein interactions (PPI) and hub genes were discovered by the DMNC and Clustering Coefficient algorithms. Receiver operating characteristic (ROC) analysis and expression profiling were undertaken to determine diagnostic performance. In vitro assays, including CCK-8 assays, clonogenic assays, flow cytometry, dot blots, co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and Western blots, were applied to evaluate the role of CDCA7 and its interaction with helicase, lymphoid-specific (HELLS).

169 overlapping genes were discovered, enriched in Cell adhesion molecules and ECM-receptor interaction. CDCA7 is highly expressed in GC and has high clinical diagnostic value. Knockdown of CDCA7 causes apoptosis and suppresses GC cell invasion, migration, and proliferation. Mechanistically, CDCA7 physically interacts with HELLS and promotes HELLS recruitment to chromatin. Knockdown of CDCA7 reduces global 5 hmC/5 mC levels and histone methylation (H3K9me3 and H4K20me3), while HELLS overexpression partially reverses these effects. Functionally, HELLS overexpression also partially reverses the antiproliferative and proapoptotic effects of CDCA7 knockdown.

CDCA7 promotes GC progression by interacting with HELLS to regulate DNA methylation and chromatin stability, suggesting that the CDCA7-HELLS axis may serve as a potential diagnostic biomarker and therapeutic target for GC.