Bromodomain containing 4 transcriptionally activated Deltex E3 ubiquitin ligase 2 contributes to glioma progression and predicts an unfavorable prognosis

Wu, Shizhong; Shen, Shuiwen; Lu, Feng; Zheng, Pengfeng; Lin, Kun; Liao, Jingwei; Jiang, Xiaohang; Zeng, Guangming; Wei, De

doi:10.21037/atm-22-555

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…The characteristics of members of this family include a conserved C terminus consisting of a RING and DTC domain [ 11 ]. DTX2 has been reported to be involved in many human cancers with functions as an oncogene and can be used as a prognostic marker [ 5 , 8 ]. In this study, we showed that the high expression of DTX2 in glioma tissues was associated with poor patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…proposed DTX2 as part of an 18-gene panel of prognostic biomarkers whose expression is related to poor outcomes in metastatic breast cancer [ 7 ]. BRD4 transcriptionally activates DTX2, contributing to glioma progression, and predicts an unfavorable prognosis [ 8 ]. However, studies of DTX2 in cancer have been limited, with very few reports on its role in glioma.…”

Section: Instructionsmentioning

confidence: 99%

“…Helicase-like transcription factor (HLTF), which belongs to the SWI/SNF family, participates in tumor progression in two ways: epigenetic silencing by DNA methylation, or overexpression [ 9 ]. HLTF has been identified as a tumor-suppressive biomarker that is methylated in non-small-cell lung cancer; hypermethylation of HLTF is associated with poor survival [ 8 ]. HLTF can also be used as an independent prognostic marker of tumor recurrence [ 10 ].…”

Section: Instructionsmentioning

confidence: 99%

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DTX2 promotes glioma development via regulation of HLTF

Li,

Chen,

Yang

et al. 2024

Biol Direct

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Background Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression. Methods The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy. Results DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights. Conclusions We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Section: Instructionsmentioning

confidence: 99%

Section: Instructionsmentioning

confidence: 99%

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DTX2 promotes glioma development via regulation of HLTF

Li,

Chen,

Yang

et al. 2024

Biol Direct

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“…By the same token, another study in colon cancer cells (SW620, LoVo) [ 44 ] showed DTX2 to promote migration/invasion, increase NOTCH2 levels and trigger AKT activation. Poor survival correlation with DTX2 was observed also in Glioblastoma multiforme along with the demonstration that DTX2 silencing in glioma cell lines (DBTRG, U251) inhibited both their growth and migration abilities [ 45 ]. The same study found DTX2 transcriptional activation to depend on BRD4 binding to the DTX2 promoter.…”

Section: Dtx Proteins Signaling In Mammalian and Cancer Cells: A Phos...mentioning

confidence: 99%

The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer

Scalia

Suma

Carnevale

2023

Cells

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Until recently, Deltex (DTX) proteins have been considered putative E3 ligases, based on the presence of an E3 RING domain in their protein coding sequence. The human DTX family includes DTX1, DTX2, DTX3, DTX3L and DTX4. Despite the fact that our knowledge of this class of E3-ubiquitin ligases is still at an early stage, our understanding of their role in oncogenesis is beginning to unfold. In fact, recently published studies allow us to define specific biological scenarios and further consolidate evidence-based working hypotheses. According to the current evidence, all DTX family members are involved in the regulation of Notch signaling, suggesting a phylogenetically conserved role in the regulation of this pathway. Indeed, additional evidence reveals a wider involvement of these proteins in other signaling complexes and cancer-promoting mechanisms beyond NOTCH signaling. DTX3, in particular, had been known to express two isoform variants (DTX3a and DTX3b). The recent identification and cloning of a third isoform variant in cancer (DTX3c), and its specific involvement in EphB4 degradation in cancer cells, sheds further light on this group of proteins and their specific role in cancer. Herein, we review the cumulative knowledge of this family of E3 Ubiquitin ligases with a specific focus on the potential oncogenic role of DTX isoforms in light of the rapidly expanding findings regarding this protein family’s cellular targets and regulated signaling pathways. Furthermore, using a comparative and bioinformatic approach, we here disclose a new putative motif of a member of this family which may help in understanding the biological and contextual differences between the members of these proteins.

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