CircST6GALNAC6 Inhibits Glycolysis of Bladder Cancer by Regulating PRKN/HK1 Signaling Pathway.

Abstract

Bladder cancer (BCa) is an aggressive malignancy of urinary system. Aerobic glycolysis refers to the phenomenon wherein cancer cells increase glucose consumption and produce lactic acid. Our study focused on the role and mechanism of circST6GALNAC6 in BCa glycolysis. The 24 h glucose intake was detected using flow cytometry. Lactic acid and ATP were detected in BCa cells utilizing commercially provided kits. Extracellular acidification rate was measured using Seahorse XF-96p Extracellular Flux Analyzer. Cell proliferation was determined using colony formation assay. RNA immunoprecipitation and co-immunoprecipitation experiments were adopted to validate molecular interactions. BALB/C nude mice were utilized to establish xenograft tumor model. CircST6GALNAC6 was decreased in BCa cells, and overexpression of circST6GALNAC6 inhibited glycolysis and proliferation of BCa cells. Additionally, overexpression of circST6GALNAC6 promoted the degradation of glycolytic regulatory protein HK1 and decreased its expression, and PRKN facilitated ubiquitination-related degradation of HK1. CircST6GALNAC6 enhanced the mRNA stability and expression of PRKN by recruiting FUS. Furthermore, the inhibitory impact of circST6GALNAC6 overexpression on glycolysis in BCa cells was reversed by PRKN knockdown. Finally, overexpression of circST6GALNAC6 suppressed tumor growth through increasing PRKN in nude mice. CircST6GALNAC6 suppressed glycolysis in BCa through FUS/PRKN/HK1 axis. Targeting circST6GALNAC6 holds promise as a novel approach for treating BCa.