Wild-type IDH1 inhibits the tumor growth through degrading HIF-α in renal cell carcinoma

Chen, Song; Wang, Yejinpeng; Xiong, Yaoyi; Peng, Tianchen; Lü, Mengxin; Guo, Zhongqiang

doi:10.7150/ijbs.54401

Cited by 10 publications

(12 citation statements)

References 27 publications

(11 reference statements)

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“…At present, there is little evidence related to AKG alterations in kidney diseases, such as increased urinary excretion in diabetic nephropathy in humans [ 44 ] and mice [ 78 ]; however other report decreased urinary levels in humans and mice [ 42 , 79 ] and reduction of blood serum AKG concentration in diabetic nephropathy in mice [ 41 ]. On the other hand, in RCC, contrary results were found in tissue with an elevated concentration in mice [ 80 ] compared to low levels reported in human samples [ 81 ].…”

Section: Alpha-ketoglutaratementioning

confidence: 98%

“…In CKD patients, decreased urinary levels of AKG have been reported [ 42 ], whereas there are no differences in AKI patients [ 176 ]. In RCC, AKG urinary excretion is increased [ 177 ], whereas, in biopsies, reduced levels have been reported; even more, tissue levels of this metabolite could be helpful in the prognosis of this neoplasia [ 81 ].…”

Section: Clinical Significance Of Tca Metabolitesmentioning

confidence: 99%

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Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

et al. 2021

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Mitochondria are complex organelles that orchestrate several functions in the cell. The primary function recognized is energy production; however, other functions involve the communication with the rest of the cell through reactive oxygen species (ROS), calcium influx, mitochondrial DNA (mtDNA), adenosine triphosphate (ATP) levels, cytochrome c release, and also through tricarboxylic acid (TCA) metabolites. Kidney function highly depends on mitochondria; hence mitochondrial dysfunction is associated with kidney diseases. In addition to oxidative phosphorylation impairment, other mitochondrial abnormalities have been described in kidney diseases, such as induction of mitophagy, intrinsic pathway of apoptosis, and releasing molecules to communicate to the rest of the cell. The TCA cycle is a metabolic pathway whose primary function is to generate electrons to feed the electron transport system (ETS) to drives energy production. However, TCA cycle metabolites can also release from mitochondria or produced in the cytosol to exert different functions and modify cell behavior. Here we review the involvement of some of the functions of TCA metabolites in kidney diseases.

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Section: Alpha-ketoglutaratementioning

confidence: 98%

Section: Clinical Significance Of Tca Metabolitesmentioning

confidence: 99%

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

et al. 2021

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“…Mutations in IDH1 reduce IDH1’s catalytic activity and activate HIF-1 α in glioblastoma cells ( 55 ). Wild-type IDH1 suppresses tumor development in renal cell carcinoma via degrading HIF-α ( 56 ). By using GSEA to examine the variations in cellular activities and pathways between high and low risk groups, we found that metabolic processes and pathways associated with hypoxic state were upregulated, but immune response processes were generally downregulated.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a 6-Gene Hypoxia-Related Prognostic Signature For Cholangiocarcinoma

Sun

Wang²,

Xiao

et al. 2022

Front. Oncol.

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Cholangiocarcinoma (CHOL) is highly malignant and has a poor prognosis. This study is committed to creating a new prognostic model based on hypoxia related genes. Here, we established a novel tumor hypoxia-related prognostic model consisting of 6 hypoxia-related genes by univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict CHOL prognosis and then the risk score for each patient was calculated. The results showed that the patients with high-risk scores had poor prognosis compared with those with low-risk scores, which was verified as an independent predictor by multivariate analysis. The hypoxia-related prognostic model was validated in both TCGA and GEO cohorts and exhibited excellent performance in predicting overall survival in CHOL. The PPI results suggested that hypoxia-related genes involved in the model may play a central role in regulating the hypoxic state. In addition, the presence of IDH1 mutations in the high-risk group was high, and GSEA results showed that some metabolic pathways were upregulated, but immune response processes were generally downregulated. These factors may be potential reasons for the high-risk group with worse prognosis. The analysis of different immune regulation-related processes in the high- and low-risk groups revealed that the expression of genes related to immune checkpoints would show differences between these two groups. We further verified the expression of the oncogene PPFIA4 in the model, and found that compared with normal samples, CHOL patients were generally highly expressed, and the patients with high-expression of PPFIA4 had a poor prognosis. In summary, the present study may provide a valid prognostic model for bile duct cancer to inform better clinical management of patients.

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“…Ultimately, α-ketoglutaric acid accumulation and TCA cycle obstruction 14 . On the contrary, IDH1 gene mutation results in a new activity of the isocitrate dehydrogenase (IDH) enzyme, which catalyzes the reduction of α-KG to 2HG and thus reduces the accumulation of α-KG 15 . In addition, L2HG is involved in angiogenic mimicry (VM) formation in ccRCC cell lines by decreasing PHLDB2 expression or promoting activation of erK1/2 pathway 16 .…”

Section: Metabolic Reprogramming In Tumor Cellsmentioning

confidence: 99%

Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma

Zhang¹,

Yu²,

Chen³

et al. 2022

J. Cancer

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Renal cell carcinoma (RCC), one of the most frequent cancers, is a "classical" malignancy characterized by metabolic reprogramming. Clear cell renal cell carcinoma (ccRCC) is its most common histopathological subtype. Long-stranded non-coding ribonucleic acids (LncRNAs) are regulatory RNA molecules with limited protein-coding capacity and evolutionary conservation. Recent studies have revealed that lncRNAs can broadly regulate the metabolic reprogramming of ccRCC and its malignant transformation. However, there are few studies on lncRNAs regulating the metabolism of ccRCC, and the specific mechanisms are unknown. Therefore, this paper summarizes the regulatory mechanisms of lncRNAs in the metabolism of ccRCC, especially in the pathways of glycolysis, mitochondrial function, glutamine and lipid metabolism, cellular mechanisms, interactions with other molecules, specific scientific and clinic implications and applications to provide a basis for early clinical diagnosis, prediction and treatment. We also discuss the clinical application and challenges of targeting lncRNAs in ccRCC metabolism.

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Wild-type IDH1 inhibits the tumor growth through degrading HIF-α in renal cell carcinoma

Cited by 10 publications

References 27 publications

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

Development and Validation of a 6-Gene Hypoxia-Related Prognostic Signature For Cholangiocarcinoma

Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma

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