Dataset Information

Extracellular Citrate Treatment Induces HIF1α Degradation and Inhibits the Growth of Low-Glycolytic Hepatocellular Carcinoma under Hypoxia.

ABSTRACT: HCC is well known for low glycolysis in the tumors, whereas hypoxia induces glycolytic phenotype and tumor progression. This study was conducted to evaluate the expression of SLCs in human HCCs and investigated whether extracellular nutrient administration related to SLCs in low-glycolytic HCC can prevent hypoxic tumor progression. SLCs expression was screened according to the level of glycolysis in HCCs. Then, whether extracellular nutrient treatment can affect hypoxic tumor progression, as well as the mechanisms, were evaluated in an in vitro cell line and an in vivo animal model. Low-glycolytic HCCs showed high SLC13A5/NaCT and SLC16A1/MCT1 but low SLC2A1/GLUT1 and HIF1α/HIF1α expression. Especially, high SLC13A5 expression was significantly associated with good overall survival in the Cancer Genome Atlas (TCGA) database. In HepG2 cells with the highest NaCT expression, extracellular citrate treatment upon hypoxia induced HIF1α degradation, which led to reduced glycolysis and cellular proliferation. Finally, in HepG2-animal models, the citrate-treated group showed smaller tumor with less hypoxic areas than the vehicle-treated group. In patients with HCC, SLC13A5/NaCT is an important SLC, which is associated with low glycolysis and good prognosis. Extracellular citrate treatment induced the failure of metabolic adaptation to hypoxia and tumor growth inhibition, which can be a potential therapeutic strategy in HCCs.

SUBMITTER: Kim SY

PROVIDER: S-EPMC9315704 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Extracellular Citrate Treatment Induces HIF1α Degradation and Inhibits the Growth of Low-Glycolytic Hepatocellular Carcinoma under Hypoxia.

Kim Seon Yoo SY Kim Dongwoo D Kim Jisu J Ko Hae Young HY Kim Won Jin WJ Park Youngjoo Y Lee Hye Won HW Han Dai Hoon DH Kim Kyung Sik KS Park Sunghyouk S Lee Misu M Yun Mijin M

Cancers 20220710 14

HCC is well known for low glycolysis in the tumors, whereas hypoxia induces glycolytic phenotype and tumor progression. This study was conducted to evaluate the expression of SLCs in human HCCs and investigated whether extracellular nutrient administration related to SLCs in low-glycolytic HCC can prevent hypoxic tumor progression. SLCs expression was screened according to the level of glycolysis in HCCs. Then, whether extracellular nutrient treatment can affect hypoxic tumor progression, as wel ...[more]

PMID: 35884416

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Project description:The hypoxia signaling pathway controls hypoxia adaptation and tolerance of organisms, which is regulated by multiple mechanisms. Viral infection elicits various pathophysiological responses in the host. However, whether viral infection can affect the hypoxia response is not yet fully understood. In this study, we found that Spring viremia of carp virus (SVCV) infection in zebrafish caused symptoms similar to those in zebrafish under hypoxic conditions. Further assays indicated that SVCV infection activated the hypoxia signaling pathway in zebrafish. In addition, SVCV infection caused increased glycolysis and reactive oxygen species (ROS) levels in cells. Mechanistically, SVCV-G protein interacted with hif1α-a/b and attenuated their K48-linked polyubiquitination, leading to their stabilization and subsequent enhancement of target gene expression. Moreover, treatment with the HIF1α-specific inhibitor PX478 enhanced the antiviral ability against SVCV infection in zebrafish and zebrafish cells. This study reveals a relationship between SVCV infection and the hypoxia signaling pathway in fish and provides a strategy for reducing the damage of viral disease in the aquaculture industry.ImportanceViral infection triggers various pathophysiological responses in the host. The hypoxia signaling pathway controls hypoxia adaptation and tolerance of organisms. However, whether viral infection can affect the hypoxia response is not yet fully understood. This study showed that Spring viremia of carp virus (SVCV) infection activated the hypoxia signaling pathway and induced a hypoxia response. The SVCV-G protein interacted with hif1α-a/b and reduced their K48-linked polyubiquitination, leading to their stabilization and subsequent enhancement of target gene expression. Additionally, treatment with the HIF1α-specific inhibitor PX478 enhanced the antiviral ability against SVCV infection in zebrafish and zebrafish cells. Our findings not only reveal a relationship between SVCV infection and the hypoxia signaling pathway in fish but also provide a strategy for reducing the damage of viral disease in the aquaculture industry.

Dataset Information

Extracellular Citrate Treatment Induces HIF1α Degradation and Inhibits the Growth of Low-Glycolytic Hepatocellular Carcinoma under Hypoxia.

Publications

Extracellular Citrate Treatment Induces HIF1α Degradation and Inhibits the Growth of Low-Glycolytic Hepatocellular Carcinoma under Hypoxia.

Similar Datasets

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