Expression characteristics of RFWD3 in intestinal type gastric cancer and its regulatory effects on tumor cell proliferation, invasion, and apoptosis

RFWD3 is a RING type E3 ubiquitin ligase involved in DNA damage repair and p53 regulation. Its role in intestinal type gastric cancer (IGC) remains unclear. This study aimed to investigate RFWD3 expression in IGC tissues and its effects on tumor cell proliferation, invasion, and apoptosis. RFWD3 expression was examined in 86 paired IGC and adjacent normal tissues using immunohistochemistry and RT qPCR. Associations with clinicopathological features were analyzed. RFWD3 was silenced by siRNA in AGS and HGC 27 cells. Cell proliferation, migration, invasion, cell cycle distribution, and apoptosis were evaluated by CCK 8, colony formation, Transwell assays, and flow cytometry, respectively. Related protein expression was detected by Western blotting. RFWD3 was significantly upregulated in IGC tissues at both mRNA and protein levels. High RFWD3 expression was associated with poor differentiation, deeper invasion, lymph node metastasis, and advanced TNM stage. RFWD3 knockdown inhibited cell proliferation, suppressed migration and invasion, induced G2/M phase arrest, and promoted apoptosis. Mechanistically, RFWD3 silencing downregulated Bcl 2 and MMP 9 while upregulating Bax, cleaved caspase 3, and E cadherin. RFWD3 is overexpressed in IGC and promotes tumor progression by enhancing proliferation and invasion while inhibiting apoptosis. As survival outcomes were not analysed in this cohort, RFWD3 should be regarded as a candidate marker of aggressive disease and a potential therapeutic target in intestinal type gastric cancer, pending validation in cohorts with survival follow up. Not applicable.