Primase subunit 2 regulates the proliferation and apoptosis of gastric cancer cells via MCM7/CDK4 and Bax/Bcl-2 pathways.

BACKGROUND

PRIM2 (DNA primase subunit 2), a key regulator of DNA replication initiation, is aberrantly expressed in multiple cancer types and contributes to tumor progression.

OBJECTIVE

This study aimed to investigate the expression of PRIM2 in GC and its effects on cell proliferation and apoptosis, particularly through the MCM7/CDK4 and Bax/Bcl-2 pathways.

METHODS

PRIM2 expression in gastric cancer (GC) and adjacent normal tissues was analyzed using TCGA data, and Kaplan-Meier analysis evaluated its prognostic value. PRIM2 was knocked down or overexpressed in GC cell lines. Western blot measured PRIM2, MCM7, CDK4, Bax, and Bcl-2. Cell proliferation and apoptosis were assessed by CCK-8, colony formation, and flow cytometry. RNA-seq with GO/KEGG analyses and a nude mouse xenograft model examined pathways and in vivo growth.

RESULTS

PRIM2 was highly expressed in GC tissues and cell lines, and its elevated expression was significantly correlated with poor 5-year progression-free survival (PFS) and overall survival (OS) in GC patients. PRIM2 knockdown significantly inhibited proliferation of AGS and HGC-27 cells, whereas PRIM2 overexpression promoted proliferation. Apoptosis was increased upon PRIM2 knockdown. Transcriptomic analysis revealed that PRIM2 knockdown primarily affected the MCM7/CDK4 and Bax/Bcl-2 pathways, which was further confirmed by Western blot. In vivo, PRIM2 knockdown markedly suppressed tumor growth in the xenograft model.

CONCLUSION

PRIM2 regulates GC cells proliferation and apoptosis by the MCM7/CDK4 and Bax/Bcl-2 pathways. Future studies should further investigate the interactions between PRIM2 and other downstream pathways, as well as elucidate its specific mechanisms of action in tumor tissues.