SPC25 promotes gastric cancer cells G1/S cell cycle transition and tumorigenesis by enhancing SLC1A5-mediated glutamine metabolism.

Although spindle pole body component 25 (SPC25) has been implicated in various cancers, its precise role in GC remains unexplored. This study aimed to investigate the role and mechanism of SPC25 in GC progression. SPC25 expression was analyzed using TCGA database and 40 paired GC clinical specimens. RT-qPCR, Western blot and immunohistochemistry (IHC) staining were performed to detect the expression of SPC25 in GC samples. Flow cytometry was conducted to assess the cell cycle, and commercial kits were used to measure the levels of glutamine, glutamic acid, α-Ketoglutaric acid (α-KG) and NADPH/NADP+. MeRIP-PCR was employed to explore the regulatory role of SPC25 on the m6A levels of SLC1A5. RNA immunoprecipitation (RIP) assay to test the binding between IGF2BP2 and SPC25 transcripts. Xenograft mouse model was constructed to assess the effect of SPC25 on tumor growth in vivo. SPC25 was significantly overexpressed in GC tissues and cell lines. Silencing SPC25 repressed G1/S cell cycle transition and downregulated the expressions of several key mitotic regulators. Moreover, the interference of SPC25 repressed glutamine metabolism in GC cells, as demonstrated by reduced glutamine consumption and decreased production of α-KG, glutamate and NADPH/NADP+. SPC25 overexpression exerted the opposite effects. Mechanistically, SPC25 promoted glutamine metabolism and cell cycle progression in GC by stabilizing SLC1A5 expression through IGF2BP2-mediated m6A modification. Animal study revealed that SPC25 knockdown suppressed tumor growth in vivo. SPC25, stabilizing SLC1A5 expression through IGF2BP2 mediated m6A modification, regulated glutamine metabolism, promoted gastric cancer cells G1/S cell cycle transition and drove tumor progression.