NYCSEA

Abstract: Hepatocellular carcinoma (HCC) accounted for an estimated 660,000 deaths in 2020, and the prevalence of HCC is expected to increase by over 55% between 2020 and 2040. Due to the lack of an effective treatment for late-stage HCC, the five-year survival rate is less than 20%. Pyruvate kinase molecule 2 (PKM2) is a rate-limiting enzyme that mediates the last step of glycolysis, catalyzing the breakdown of phosphoenolpyruvate into pyruvate. Upon PKM2 upregulation, cancer cells reprogram their host’s metabolic pathways, increasing glucose uptake and evoking fermentation of glucose to lactate. This altered metabolism allows rapid production of ATP, promoting cancer cell proliferation. This study found that liver-specific knockout of the SPTBN1 gene significantly decreases PKM2 levels and prevents inflammation, cell proliferation, and abnormal vascular development. Immunohistochemical (IHC) staining with the PKM2 antibody was performed on paraffin-embedded liver tissue slides from wild-type (WT) mice, WT mice chemically induced with HCC, and HCC mice that had the SPTBN1 gene knocked out in the liver. After IHC staining, the tissue slides were photographed under a light microscope and analyzed in ImageJ, where PKM2 expression was calculated. Results of the IHC staining were also used to assess the severity of symptoms in each group of mice. This study found evidence suggesting SPTBN1 targeted gene knockout therapy may ameliorate HCC-induced symptoms and inhibit HCC development.

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