PROX1-mediated epigenetic silencing of contributes to proliferation and glucose metabolism in colorectal cancer.

Prospero-related homeobox 1 (PROX1) is a homeobox transcription factor known to promote malignant transformation and stemness in human colorectal cancer (CRC). However, the biological function of PROX1 in metabolic rearrangement in CRC remains unclear. Here, we aimed to uncover the relationship between the expression profile and role of PROX1 and CRC cell glucose metabolism and to elucidate the underlying molecular mechanism. PROX1 expression was significantly upregulated in human CRC tissues and positively associated with the maximum standardized uptake value (SUVmax), a measure of tissue 18-fluoro-2-deoxy-D-glucose uptake and an indicator of glycolysis and tumor cell activity, in patients with CRC. Knockdown of PROX1 suppressed CRC cell proliferation and glucose metabolism and . Mechanistically, through a physical interaction, PROX1 recruited EZH2 to the SIRT3 promoter and inhibited promoter activity. Moreover, PROX1 or EZH2 knockdown decreased cell glycolysis by targeting . Clinically, high PROX1 expression combined with low expression predicted poor prognosis in patients with CRC. Thus, our study suggests that the PROX1-EZH2 complex positively regulates cell proliferation and glucose metabolism by engaging in CRC, which may serve as a promising therapeutic strategy for CRC.