Downregulating FGGY carbohydrate kinase domain containing promotes cell senescence by activating the p53/p21 signaling pathway in colorectal cancer.

Abstract

Carbohydrate kinases serve an oncogenic role in several types of cancer; however, the function of FGGY carbohydrate kinase domain containing (FGGY) in colorectal cancer (CRC) remains unknown. The present study investigated the function and possible molecular mechanisms of FGGY in CRC. The results showed that elevated levels of FGGY mRNA and protein were observed in CRC tissues, and a higher expression of FGGY was associated with advanced N stage and reduced overall survival time in patients with CRC. Silencing FGGY inhibited the viability of CRC cells by inducing cell cycle arrest and promoting apoptosis in vitro, thereby attenuating tumor growth in a xenograft mouse model. FGGY knockdown also enriched the senescence‑associated heterochromatin foci (SAHF) pathway and p53 pathway, as further confirmed by enhancing senescence‑associated β‑galactosidase (SA‑β‑gal) activity, with increased levels of SAHF‑associated proteins HP1γ and trimethylation of H3K9 (H3k9me3) in CRC cells, as well as upregulation of p53 and its downstream protein p21. Furthermore, p53 knockout rescued FGGY knockdown‑mediated reductions in cell viability, SA‑β‑gal activity, and the levels of HP1γ and H3k9me3 in CRC cells. These findings indicated that FGGY could act as a newly identified potential oncogene in CRC, partially through regulating the p53/p21 signaling pathway and altering cell senescence.