Modulating the Biological Processes and Glycolysis of Hepatocellular Carcinoma Cells by UBR7’s Suppression of Pyruvate Kinase PKM2

As a key glycolytic enzyme, Pyruvate kinase M2 (PKM2), which is highly expressed in cancer cells, promotes hepatocellular carcinoma (HCC) proliferation/metastasis. This research investigates the involvement of Ubiquitin protein ligase E3 component N-recognin 7 (UBR7) in HCC progression/glycolysis and its potential mechanisms.

UBR7 expressions in HHL-5, Huh-7, and HepG2 cells were investigated using Quantitative Reverse Transcription Polymerase Chain Reaction and Western Blot. Cell counting kit-8, clone formation experiment, scratch-wound assay, and transwell testing were conducted to assess the malignant biological behaviors of HepG2 and Huh-7 cells; the absorption level of glucose and generation levels of lactic acid and ATP were tested by assay kits. Huh-7 cells with stably overexpressed or knocked down UBR7 were inoculated into nude mice. Regular measurements were conducted on the tumor size, the tumors were isolated and weighed on the 35th day, and the glycolytic level in the tumor tissues was determined.

In HCC cells, UBR7 was significantly downregulated. Notably, UBR7 knockdown promoted HCC progression and glycolysis, increasing the viability of HepG2 and Huh-7 cells by 23%–24% (p < 0.001), whereas UBR7 overexpression exerted the opposite inhibitory effects, resulting in a reduction of about 19%–31% in cell viability (p < 0.001). UBR7 knockdown upregulated PKM2 expression in HCC cells, while UBR7 overexpression led to a marked reduction in PKM2 levels. Importantly, PKM2 overexpression partly abrogated the inhibitory impacts of UBR7 on HCC progression and glycolysis. In vivo experiments further demonstrated that UBR7 overexpression suppressed tumor growth and hindered glycolysis in nude mice.

UBR7 suppressed PKM2 expression, thus hindering malignant biological progression and glycolysis in HCC, providing a potential therapeutic target for HCC treatment.