ZHX2 in health and disease

Li, Na; Wu, Zhuanchang; Ma, Chunhong

doi:10.3389/fonc.2022.1038890

Cited by 6 publications

(4 citation statements)

References 83 publications

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“…Furthermore, the regulation mediated by PPAR, influencing thyroid peroxidase, thyroglobulin, and thyrotropin receptor gene promoters, facilitates the intricate process of thyroid cell differentiation [44]. These insights shed light on the intricate interplay between signaling pathways and genetic alterations, offering valuable perspectives into the molecular landscape of THCA pathogenesis [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. The tumor microenvironment has garnered recognition as a crucial determinant influencing tumor initiation, progression, treatment response, and prognosis [45].…”

Section: Discussionmentioning

confidence: 99%

“…Silencing ACTN1 expression has been demonstrated to impede the proliferation of hepatocellular carcinoma (HCC) [ 31 ]. ZHX2, recognized as a tumor suppressor gene, orchestrates lipid metabolism regulation, suppresses cell proliferation [ 32 ], and influences the immune microenvironment [ 33 ]. Notably, ZHX2 has been implicated in the occurrence of brain metastasis in THCA [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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Identification of disulfidptosis-associated genes and characterization of immune cell infiltration in thyroid carcinoma

Song,

Zhou,

Zhang

et al. 2024

Aging

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Objective: The primary objective of this study is to conduct a comprehensive screening and analysis of differentially expressed genes related to disulfidoptosis (DEDRGs) in thyroid carcinoma (THCA). This entails delving into the intricate characterization of immune cell infiltration within the THCA context and subsequently formulating and validating a novel prognostic model. Method: To achieve our objectives, we first delineated two distinct subtypes of disulfidoptosis-related genes (DRGs) via consensus clustering methodology. Subsequently, employing the limma R package, we identified the DEDRGs critical for our investigation. These DEDRGs underwent meticulous validation across various databases, alongside an in-depth analysis of gene regulation. Employing functional enrichment techniques, we explored the potential molecular mechanisms underlying disulfidoptosis in THCA. Furthermore, we scrutinized the immune landscape within the two identified subtypes utilizing CIBERSORT and ESTIMATE algorithms. The construction of the prognostic model for THCA entailed intricate methodologies including univariate, multivariate Cox regression, and LASSO regression algorithms. The validity and efficacy of our prognostic model were corroborated through Kaplan-Meier survival curves and ROC curves. Additionally, a nomogram was meticulously formulated to facilitate the prediction of patient prognosis. To fortify our findings, we conducted a comprehensive Bayesian co-localization analysis coupled with rigorous in vitro experimentation, aimed at unequivocally establishing the validity of the identified DEDRGs. Result: Our analyses unveiled Cluster C1, characterized by elevated expression levels of DEDRGs, as harboring a favorable prognosis accompanied by abundant immune cell infiltration. Correlation analyses underscored predominantly positive associations among the DEDRGs, further affirming their significance in THCA. Differential expression patterns of DEDRGs between tumor samples and normal tissues were evident across the GEPIA and HPA databases. Insights from the TIMER database underscored a robust correlation between DEDRGs and immune cell infiltration. KEGG analysis elucidated the enrichment of DEDRGs primarily in pivotal pathways including MAPK, PPAR signaling pathway, and Proteoglycans in cancer. Furthermore, analyses using CIBERSORT and ESTIMATE algorithms shed light on the crucial role played by DEDRGs in shaping the immune microenvironment. The prognostic model, anchored by five genes intricately associated with THCA prognosis, exhibited commendable predictive accuracy and was intricately linked to the tumor immune microenvironment. Notably, patients categorized with low-risk scores stood to potentially benefit more from immunotherapy. The validation of DEDRGs unequivocally underscores the protective role of INF2 in THCA. Conclusion: In summary, our study delineates two discernible subtypes intricately associated with DRGs, revealing profound disparities in immun...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of disulfidptosis-associated genes and characterization of immune cell infiltration in thyroid carcinoma

Song,

Zhou,

Zhang

et al. 2024

Aging

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“…More and more evidence shows that ZHX2 is an important regulator of various biological processes, including regulating the development of various cancers such as liver cancer, gastric cancer, and thyroid cancer, and participating in lipid metabolism, cell differentiation, and development, NK cell maturation, and macrophage cell polarization, etc (33). Many literatures have reported that ZHX2 has an inhibitory effect on the proliferation and migration of different types of cells (17,21,(34)(35)(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

ZHX2 alleviates vascular remodeling and smooth muscle cell proliferation by transcriptional regulation of GADD45G

Fan,

Yang,

et al. 2023

Preprint

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ObjectiveThis study explores the role of ZHX2 in vascular remodeling, specifically focusing on its effects on VSMC proliferation, migration, and neointima formation following vascular injury. Methods and Results: Data from both human atherosclerotic samples and a mouse carotid injury model indicated a decrease in ZHX2 levels.In vivo, ZHX2 overexpression reduced neointima formation in mice subjected to carotid artery ligation.In vitro, ZHX2 inhibited the proliferation and migration of primary VSMCs. Conversely, specific knockout of ZHX2 in SMCsin vivoor knockdown of ZHX2 in primary VSMCs had opposite effects. RNA- seq analysis revealed that ZHX2 overexpression significantly affected the expression of cell cycle-related genes. Using Chromatin Immunoprecipitation Sequencing (ChIP-seq) and luciferase reporter assays, we demonstrated that ZHX2 plays a crucial role in the transcriptional regulation of GADD45G, identifying GADD45G as the downstream target responsible for ZHX2-mediated effects. Conclusions: ZHX2 emerges as a key player in pathological vascular remodeling, suppressing VSMC proliferation and migration through its regulatory impact on GADD45G transcription and cell cycle-related gene expression.

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“…It has been demonstrated that the VHL loss of tumor suppressor gene VHL in ccRCC resulted in the accumulation of ZHX2 protein in the nucleus and the subsequent decrease in patient survival rate [ 13 , 15 ]. More importantly, Li et al identifies ZHX2 acting as an oncogenic driver in ccRCC where hypoxia-inducible factors (HIF1 and HIF2) are deregulated [ 16 ]. ZHX2 drives proliferation, migration, colony formation and invasion via activating multiple proteins including Twist, Snail, VEGF, MEK, ERK 1/2 [ 12 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Sunitinib Treatment of VHL C162F Cells Slows Down Proliferation and Healing Ability via Downregulation of ZHX2 and Confers a Mesenchymal Phenotype

Buart,

Diop,

Damei

et al. 2023

Cancers

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von Hippel-Lindau (VHL) disease, due to mutations of the tumor suppressor VHL gene, is a rare hereditary syndrome with a high risk of developing clear cell renal cell carcinoma (ccRCC). We asked whether the VHL-C162F mutation interferes with proliferation, migration, healing and forming colony ability by using wild-type VHL (WT VHL) and VHL-C162F reconstituted cells. We then analyzed the in vitro impact of the sunitinib treatment on VHL-C162F cells. We showed that VHL-C162F mutations have no impact on cell morphology, colony formation and migration ability but confer a significant higher healing ability than in WT VHL cells. RNA sequencing analysis revealed that VHL-C162F mutation upregulates genes involved in hypoxia and epithelial mesenchymal transition (EMT) pathways by comparison with VHL WT cells. We next showed a decrease in healing ability in VHL-C162F cells depleting on ZHX2, an oncogenic driver of ccRCC, highlighting the potential involvement of ZHX2 in aggressiveness of the VHL-C162F cells. Moreover, we found that sunitinib treatment inhibits ZHX2 expression and induces a reduced proliferation correlating with downregulation of P-ERK. Sunitinib treatment also conferred a more mesenchymal profile to VHL-C162F cells with significant downregulation of E-cadherin and upregulation of N-cadherin, Slug and AXL. Sunitinib therapy may therefore promote disease progression in VHL-C162F patients.

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ZHX2 in health and disease

Cited by 6 publications

References 83 publications

Identification of disulfidptosis-associated genes and characterization of immune cell infiltration in thyroid carcinoma

Identification of disulfidptosis-associated genes and characterization of immune cell infiltration in thyroid carcinoma

ZHX2 alleviates vascular remodeling and smooth muscle cell proliferation by transcriptional regulation of GADD45G

Sunitinib Treatment of VHL C162F Cells Slows Down Proliferation and Healing Ability via Downregulation of ZHX2 and Confers a Mesenchymal Phenotype

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