E2F1‐activated SPIN1 promotes tumor growth via a MDM2‐p21‐E2F1 feedback loop in gastric cancer

Abstract

Gastric cancer (GC) is one of the most common cancers around the world. Searching for specific gene expression changes during the development of GC could help identify potential therapy targets. We previously showed that the histone code reader SPIN1 may act as an oncogene in breast cancer. At present, the biological function and regulation of SPIN1 in GC remain unclear. Here, we demonstrate that SPIN1 is upregulated in GC tissues, compared with nontumorous gastric tissues. Increased expression of SPIN1 is closely associated with poor prognosis for patients with GC. Increased SPIN1 expression enhances GC cell proliferation, migration, and invasion and promotes cell cycle progression. Mechanically, SPIN1 sustains GC cell proliferation via activation of the MDM2-p21-E2F1 signaling pathway by binding to H3K4me3 of the MDM2 promoter region. Interestingly, E2F1 could directly bind to the SPIN1 promoter and activate its transcription, thus forming a positive feedback loop. Our data suggest that SPIN1 plays an important role in the development of GC and could be used as a promising prognostic biomarker and therapeutic target for GC.