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

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Bladder cancer (BCa) is an aggressive malignancy.
• Aerobic glycolysis is a hallmark of cancer cells, involving increased glucose consumption and lactic acid production.
• Understanding the regulatory mechanisms of BCa glycolysis is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role and mechanism of circST6GALNAC6 in regulating glycolysis and proliferation in bladder cancer.
• To elucidate the molecular pathway through which circST6GALNAC6 exerts its effects.

Main Methods:

• Flow cytometry for glucose intake, commercial kits for lactic acid and ATP detection.
• Seahorse XF-96p Analyzer for extracellular acidification rate, colony formation assay for cell proliferation.
• RNA immunoprecipitation, co-immunoprecipitation, and xenograft tumor models in nude mice.

Main Results:

• circST6GALNAC6 expression was decreased in BCa cells.
• Overexpression of circST6GALNAC6 inhibited BCa cell glycolysis and proliferation.
• circST6GALNAC6 promoted PRKN-mediated degradation of HK1 by enhancing PRKN mRNA stability via FUS.
• PRKN knockdown reversed the inhibitory effects of circST6GALNAC6 on glycolysis.
• circST6GALNAC6 overexpression suppressed tumor growth in vivo.

Conclusions:

• circST6GALNAC6 suppresses bladder cancer glycolysis and proliferation via the FUS/PRKN/HK1 axis.
• circST6GALNAC6 holds promise as a novel therapeutic target for bladder cancer.