Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer

Cheng, Anqi; Guo, Xiong; Dai, Xinglong; Wang, Ziwei

doi:10.1002/2211-5463.13160

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…Consistent with findings in HCC, low ZHX2 expression correlates with poor prognosis of thyroid cancer (7), multiple myeloma (8)(9)(10), and chronic lymphocytic leukemia (11,12). On the contrary, ZHX2 promotes the development of ccRCC (13)(14)(15), TNBC (16), and gastric cancer (17,18). Beyond regulating cancer development, the latest reports have shown that ZHX2 involves in several other physiological or pathological processes, including cell differentiation and development (19)(20)(21), lipid metabolism (22)(23)(24), and viral replication (25,26).…”

Section: Introductionsupporting

confidence: 63%

“…In addition, Zhu et al reported that ZHX2 promotes cell growth and migration through activating MEK/ ERK pathway and mediates Sunitinib resistance by regulating the autophagy in ccRCC (14). A similar phenomenon is found in studies of multiple osteosarcoma and gastric cancer (17,18), where high expression of ZHX2 shows a significant correlation with poor survival. Further, a recent study clarified that ZHX2 functions as a cofactor of the HIF1a to promote HIF1a oncogenic signaling in TNBC (16).…”

Section: Oncogenic Role Of Zhx2 In Ccrcc Tnbc and Other Tumorsmentioning

confidence: 53%

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ZHX2 in health and disease

2022

Front. Oncol.

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As a transcriptional factor and the negative regulator of alpha fetal protein (AFP), Zinc fingers and homeoboxes 2 (ZHX2) has a well-established role in protection against hepatocellular carcinoma (HCC). However, recent studies have suggested ZHX2 as an oncogene in clear cell renal cell carcinoma (ccRCC) and triple-negative breast cancer (TNBC). Moreover, mounting evidence has illustrated a much broader role of ZHX2 in multiple cellular processes, including cell proliferation, cell differentiation, lipid metabolism, and immunoregulation. This comprehensive review emphasizes the role of ZHX2 in health and diseases which have been more recently uncovered.

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Section: Introductionsupporting

confidence: 63%

Section: Oncogenic Role Of Zhx2 In Ccrcc Tnbc and Other Tumorsmentioning

confidence: 53%

ZHX2 in health and disease

2022

Front. Oncol.

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“…On the other hand, from tissue microarray and clinicopathological analyses, ZHX2 protein expression in metastatic HCC was twice as high as in the primary lesions, indicating that ZHX2 expression is associated with metastasis in HCC ( 16 ). Recently, our research and others have established the oncogenic role of ZHX2 in various cancers, including ccRCC, breast cancer, multiple myeloma, and gastric cancer ( 4 , 17 – 21 ). More interestingly, ZHX2 is localized on the 8q24 locus, where Myc is localized, and this locus has been reported to be amplified in many cancers, including breast cancer ( 22 ).…”

mentioning

confidence: 87%

USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer

Xie

Zhang

Liu

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Clear cell renal cell carcinoma (ccRCC) is characterized by the loss of tumor suppressor Von Hippel Lindau (VHL) function. VHL is the component of an E3 ligase complex that promotes the ubiquitination and degradation of hypoxia inducible factor α (HIF-α) (including HIF1α and HIF2α) and Zinc Fingers And Homeoboxes 2 (ZHX2). Our recent research showed that ZHX2 contributed to ccRCC tumorigenesis in a HIF-independent manner. However, it is still unknown whether ZHX2 could be modified through deubiquitination even in the absence of pVHL. Here, we performed a deubiquitinase (DUB) complementary DNA (cDNA) library binding screen and identified USP13 as a DUB that bound ZHX2 and promoted ZHX2 deubiquitination. As a result, USP13 promoted ZHX2 protein stability in an enzymatically dependent manner, and depletion of USP13 led to ZHX2 down-regulation in ccRCC. Functionally, USP13 depletion led to decreased cell proliferation measured by two-dimensional (2D) colony formation and three-dimensional (3D) anchorage-independent growth. Furthermore, USP13 was essential for ccRCC tumor growth in vivo, and the effect was partially mediated by its regulation on ZHX2. Our findings support that USP13 may be a key effector in ccRCC tumorigenesis.

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“…The databases UALCAN (http://ualcan.path.uab.edu/) [18] and the Human Protein Atlas (https://www.proteinatlas.org/) [19] were searched for analysis of the HAUS5 mRNA levels in the dataset TCGA and HAUS5 protein levels, respectively. The Kaplan-Meier Plotter (https://kmplot.com/analysis/) [20] was employed to examine the associations between HAUS5 levels and patient survival rates. The database LinkedOmics (http://www.linkedomics.org/login.php) [21] was utilized to conduct pathway analysis and functional annotation of genes, whereas the two expression groups were subjected to Gene set enrichment analysis (GSEA) [22] concerning their differences in biological and functional pathways.…”

Section: Bioinformatic Analysismentioning

confidence: 99%

HAUS5 is a novel prognostic biomarker for hepatocellular carcinoma that is associated with poor clinical outcomes

liu

Liang

et al. 2023

Preprint

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Background The Augmin Like Complex Subunit 5 (HAUS5) is involved in microtubule generation and centrosome assembly. Loss of HAUS5 function leads to loss of centrosome integrity, ultimately promoting tumor formation by causing functional defects and chromosome dislocation in the bipolar spindle. However, the role of HAUS5 in the development and progression of hepatocellular carcinoma (HCC) remains unclear. Methods and results This research dealt with investigating the role of HAUS5 in HCC and reported that HAUS5 is over-expressed in HCC tissues and cells. It was also found that its high expression levels were a crucial risk factor that affected HCC patients’ survival status. Correlation analysis depicted that HAUS5 expression was linked to immune infiltration in HCC. A nomogram model with good predictive capability with an area under the curve (AUC) value of 0.969 was constructed by integrating the clinical features of HCC and HAUS5 expression levels. HAUS5 knockdown remarkably attenuated the migration abilities and invasiveness of HCC cells. Conclusion HAUS5 is over-expressed in HCC tissues and could be used as a novel prognostic biomarker for patients with HCC.

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Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer

Cited by 9 publications

References 30 publications

ZHX2 in health and disease

ZHX2 in health and disease

USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer

HAUS5 is a novel prognostic biomarker for hepatocellular carcinoma that is associated with poor clinical outcomes

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