ZEB1 Transcriptionally Activates PHGDH to Facilitate Carcinogenesis and Progression of HCC

Wang, Huihui; Lin, Furong; Xu, Zhenzhen; Yu, Shengnan; Li, Guannan; Liao, Shan; Zhao, Wentao; Zhang, Fengqiong; Wang, Jinyang; Wang, Shijie; Ouyang, Cong; Zhang, Cixiong; Xia, Hailong; Wu, Yangjun; Jiang, Bin; Li, Qinxi

doi:10.1016/j.jcmgh.2023.06.006

Cited by 9 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PHGDH is a crucial serine biosynthesis enzyme. Research has shown that PHGDH is excessively produced in HCC cells, and suppressing PHGDH expression may substantially impact cancer cell proliferation, migration, and invasion [ 44 ]. Increasing the ubiquitination degradation of PHGDH may effectively suppress the growth of HCC cells and the characteristics of cancer stem cells [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis

Ma,

Tang,

Yao

et al. 2024

JPM

View full text Add to dashboard Cite

Background: Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed. Methods: This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC. Results: A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause–effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC. Conclusions: Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.

show abstract

Section: Discussionmentioning

confidence: 99%

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis

Ma,

Tang,

Yao

et al. 2024

JPM

View full text Add to dashboard Cite

show abstract

“…In a recent research article published in Cellular and Molecular Gastroenterology and Hepatology , 3 a team of scientists led by Li and Jiang, explored the function of ZEB1 in modulating the metabolic reprogramming of HCC. The researchers developed a liver-specific ZEB1 knockout mouse model and discovered that ZEB1 knockout hindered the formation of N-nitrosodiethylamine (DEN)-carbon tetrachloride (CCl4)-induced HCC, indicating the crucial role of ZEB1 in HCC development.…”

mentioning

confidence: 99%

“…The impairment of SSP in ZEB1 knockdown HCC cells was owing to the down-regulation of PHGDH. Wang et al 3 showed that ZEB1 binds to the promoter of PHGDH between -254 to -214 nt, thus activating the expression of PHGDH. [U- 13 C]-glucose tracing experiments further confirmed that 3-phosphoglycerate, the substrate of PHGDH, was accumulated upon ZEB1 knockdown, while the products of SSP, such as 3PS, serine, and glycine, were depleted.…”

mentioning

confidence: 99%

“…The inactivation of PHGDH by small-molecule inhibitors has been shown to suppress HCC growth and sensitize sorafenib treatment. 4 The findings from Li and Jiang's groups 3 illustrate the role of PHGDH in ZEB1-mediated HCC metastasis, highlighting the opportunity to use PHGDH inhibitors as an adjuvant treatment to prevent postoperative HCC recurrence. This study not only sheds light on the complex molecular mechanisms behind HCC development and progression, but also highlights promising therapeutic avenues for future research.…”

mentioning

confidence: 99%

See 1 more Smart Citation