The deubiquitinating enzyme ATXN3 promotes the progression of anaplastic thyroid carcinoma by stabilizing EIF5A2

Zhuang, Shimin; Xie, Jing; Jing, Zhen; Guo, Liangyun; Zhou, Hong; Li, Feihong; Xu, Debin

doi:10.1016/j.mce.2021.111440

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…Recent studies reported that oral squamous cell carcinoma (OSCC) (Song et al, 2021), testicular cancer (TC) (Shi et al, 2018), colon cancer (Li et al, 2019), breast cancer (BC) (Zou et al, 2019), anaplastic thyroid carcinoma (ATC) (Zhuang et al, 2021), neuroblastoma (NB) (Gong et al, 2021), non-small cell lung cancer (NSCLC) (Sacco et al, 2014), and breast cancer stem cells (Zhu et al, 2019)were closely related to ATXN3. For example, for oral squamous cell carcinoma, it had been studied that down-regulated miR-619-5p promoted the proliferation, migration, and invasion abilities by enhancing ATXN3 expression in OSCC cisplatin-resistant cells.…”

Section: Discussionmentioning

confidence: 99%

“…As expected, the biological functions of MJDs family members primarily correlated with ubiquitin mediated proteolysis, Th17 cell differentiation, valine, leucine and isoleucine degradation, glycine serine and threonine metabolism, and oxidative phosphorylation. It was reported that MJDs family members involve multiple signaling pathways, including ubiquitin pathway (Zhuang et al, 2021), apoptosis (Li et al, 2019), Hedgehog signaling pathway (Xu et al, 2021), JAK2 (Yang et al, 2022), and Akt/PI3K signaling (Sacco et al, 2014). In addition, a previous study reported that the serine-biosynthesis pathway and tyrosine-relative kinase inhibitors played important regulatory roles in tumor progression and immunotherapy in liver cancer patients (Sangro et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…The MJDs family members is of critical importance in tumorigenesis and tumor progression (Zeng et al, 2020). For example, downregulation of ATXN3 promotes sensitivity of neuroblastoma cells to Perifosine and MK-2206, but reduces sensitivity to etoposide and cisplatin in these cells (Gong et al, 2021); ATXN3 enhances breast cancer (BRCA) metastasis by deubiquitinating KLF4 (Zou et al, 2019); ATXN3 promotes mRNA expression of EIF5A2 by stabilizing EIF5A2 to decrease its ubiquitination and degradation in anaplastic thyroid carcinoma (Zhuang et al, 2021). Down-regulation of ATXN3L suppresses breast cancer cell proliferation by directly binding to KLF5 (Ge et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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MJDs family members: Potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma

et al. 2022

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Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies. It is not easy to be diagnosed in the early stage and is prone to relapse, with a very poor prognosis. And immune cell infiltration and tumor microenvironment play important roles in predicting therapeutic response and prognosis of HCC. Machado-Joseph domain-containing proteases (MJDs), as a gene family extensively involved in tumor progression, has pro-cancer and anti-cancer effects. However, the relationship between MJDs family members and immune cell infiltration and tumor microenvironment in HCC remains unclear. Therefore, cBio Cancer Genomics Portal (cBioPortal), The Cancer Genome Atlas (TCGA), UALCAN, Human Protein Atlas (HPA), MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were performed to investigate the mRNA expression, DNA methylation, clinicopathologic features, immune cell infiltration and other related functions of MJDs family members in HCC. The results indicated that the expression of ATXN3, JOSD1, and JOSD2 was dramatically increased in HCC tissues and cell lines, and was correlated with histological grade, specimen type, TP53 mutation, lymph node metastatic, gender, and age of patients with HCC. Meanwhile, these genes also showed clinical value in improving the overall survival (OS), disease-specific survival (DSS), progression free survival (PFS), and relapse-free survival (RFS) in patients with HCC. The prognostic model indicated that the worse survival was associated with overall high expression of MJDs members. Next, the results suggested that promotor methylation levels of the MJDs family were closely related to these family mRNA expression levels, clinicopathologic features, and prognostic values in HCC. Moreover, the MJDs family were significantly correlated with CD4+ T cells, CD8+ T cells, B cells, neutrophils, macrophages, and DCs. And MJDs family members’ expression were substantially associated with the levels of several lymphocytes, immunomoinhibitors, immunomostimulators, chemokine ligands, and chemokine receptors. In addition, the expression levels of MJDs family were significantly correlated with cancer-related signaling pathways. Taken together, our results indicated that the aberrant expression of MJDs family in HCC played a critical role in clinical feature, prognosis, tumor microenvironment, immune-related molecules, mutation, gene copy number, and promoter methylation level. And MJDs family may be effective immunotherapeutic targets for patients with HCC and have the potential to be prognostic biomarkers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MJDs family members: Potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma

et al. 2022

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“…By deubiquitinating and stabilising KLF4 and EIF5A2, ATXN3 promotes breast cancer and thyroid cancer, respectively. 45,46 As the corresponding targeting piRNAs and miRNAs of ATXN3 (Fig. 6) are downregulated, this could be the reason for the upregulation of ATXN3, which might be involved in the tumorigenesis of GBM.…”

Section: A Few Degs Are Targeted By Both Mirnas and Pirnas In Gbmmentioning

confidence: 99%

Integrative analysis of small non-coding RNAs predicts a piRNA/miRNA-CCND1/BRAF/HRH1/ATXN3 regulatory circuit that drives oncogenesis in glioblastoma

et al. 2023

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“…However, aside from its involvement in MJD, the ataxin-3 protein is intimately involved in an eclectic range of biological processes ranging from protein quality control [ 10 , 11 ], autophagy [ 12 ], transcription regulation [ 13 , 14 ], cytoskeletal regulation [ 15 , 16 ], stress responses [ 17 ], and antiviral response [ 18 ], to DNA repair [ 19 ]. Ataxin-3 has also been implicated in the progression of numerous cancers including testicular [ 20 ], breast [ 21 ], gastric [ 22 ], and thyroid cancers [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases

Potapenko,

Davidson,

Lee

et al. 2024

Biochemical Journal

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Machado-Joseph disease (MJD) is a devastating and incurable neurodegenerative disease characterised by progressive ataxia, difficulty speaking and swallowing. Consequently, affected individuals ultimately become wheelchair dependent, require constant care, and face a shortened life expectancy. The monogenic cause of MJD is expansion of a trinucleotide (CAG) repeat region within the ATXN3 gene, which results in polyglutamine (polyQ) expansion within the resultant ataxin-3 protein. While it is well established that the ataxin-3 protein functions as a deubiquitinating (DUB) enzyme and is therefore critically involved in proteostasis, several unanswered questions remain regarding the impact of polyQ expansion in ataxin-3 on its DUB function. Here we review the current literature surrounding ataxin-3's DUB function, its DUB targets, and what is known regarding the impact of polyQ expansion on ataxin-3's DUB function. We also consider the potential neuroprotective effects of ataxin-3's DUB function, and the intersection of ataxin-3's role as a DUB enzyme and regulator of gene transcription. Ataxin-3 is the principal pathogenic protein in MJD and also appears to be involved in cancer. As aberrant deubiquitination has been linked to both neurodegeneration and cancer, a comprehensive understanding of ataxin-3's DUB function is important for elucidating potential therapeutic targets in these complex conditions. In this review, we aim to consolidate knowledge of ataxin-3 as a DUB and unveil areas for future research to aid therapeutic targeting of ataxin-3's DUB function for the treatment of MJD and other diseases.

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The deubiquitinating enzyme ATXN3 promotes the progression of anaplastic thyroid carcinoma by stabilizing EIF5A2

Cited by 7 publications

References 26 publications

MJDs family members: Potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma

MJDs family members: Potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma

Integrative analysis of small non-coding RNAs predicts a piRNA/miRNA-CCND1/BRAF/HRH1/ATXN3 regulatory circuit that drives oncogenesis in glioblastoma

The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases

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