High SENP3 Expression Promotes Cell Migration, Invasion, and Proliferation by Modulating DNA Methylation of E-Cadherin in Osteosarcoma

Yang, Pu; Liu, Yan; Qi, Yin Chao; Lian, Zhao

doi:10.1177/1533033820956988

Cited by 6 publications

(4 citation statements)

References 43 publications

(51 reference statements)

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“…In mice, the deletion of SENP3 in macrophages promotes breast cancer progression and metastasis, according to recently published studies. Moreover, SENP3 may also promote cancer progression by regulating macrophage polarization ( 32 ), and high SENP3 levels are associated with more advanced tumor grades and metastasis as well as poor survival outcomes ( 33 ), meaning that SENP3 may play a role in tumorigenesis and progression. However, the function of SENP3 in TNBC is unclear.…”

Section: Discussionmentioning

confidence: 99%

SENP3 promotes tumor progression and is a novel prognostic biomarker in triple-negative breast cancer

Zhu

Zhang²,

Yu³

et al. 2023

Front. Oncol.

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BackgroundThe clinical outcome of triple-negative breast cancer (TNBC) is poor. Finding more targets for the treatment of TNBC is an urgent need. SENPs are SUMO-specific proteins that play an important role in SUMO modification. Among several tumor types, SENPs have been identified as relevant biomarkers for progression and prognosis. The role of SENPs in TNBC is not yet clear.MethodsThe expression and prognosis of SENPs in TNBC were analyzed by TCGA and GEO data. SENP3 coexpression regulatory networks were determined by weighted gene coexpression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and Cox univariate analyses were used to develop a risk signature based on genes associated with SENP3. A time-dependent receiver operating characteristic (ROC) analysis was employed to evaluate a risk signature’s predictive accuracy and sensitivity. Moreover, a nomogram was constructed to facilitate clinical application.ResultsThe prognostic and expression effects of SENP family genes were validated using the TCGA and GEO databases. SENP3 was found to be the only gene in the SENP family that was highly expressed and associated with an unfavorable prognosis in TNBC patients. Cell functional experiments showed that knockdown of SENP3 leads to growth, invasion, and migration inhibition of TNBC cells in vitro. By using WGCNA, 273 SENP3-related genes were identified. Finally, 11 SENP3-related genes were obtained from Cox univariate analysis and LASSO regression. Based on this, a prognostic risk prediction model was established. The risk signature of SENP3-related genes was verified as an independent prognostic marker for TNBC patients.ConclusionAmong SENP family genes, we found that SENP3 was overexpressed in TNBC and associated with a worse prognosis. SENP3 knockdown can inhibit tumor proliferation, invasion, and migration. In TNBC patients, a risk signature based on the expression of 11 SENP3-related genes may improve prognosis prediction. The established risk markers may be promising prognostic biomarkers that can guide the individualized treatment of TNBC patients.

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Section: Discussionmentioning

confidence: 99%

SENP3 promotes tumor progression and is a novel prognostic biomarker in triple-negative breast cancer

Zhu

Zhang²,

Yu³

et al. 2023

Front. Oncol.

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“…Mechanistically, overexpressed SENP3 in GC cells targets the EMT-inducing transcription factor forkhead box C2 (FOXC2) for desumoylation, which, in turn, activates expression of the EMT-associated and transendothelial migration-promoting N-cadherin gene ( CDH2 ), among others. In relation to this, it has also been shown that SENP3 overexpression in osteosarcoma cells results in inhibited expression of the epithelium-associated gene CDH1 , which courses with promoter hypermethylation [ 122 ]. Database analysis indicates that in general SENP3 is abundantly expressed in sarcoma and high expression correlates with poor prognosis, being shown in osteosarcoma that SENP3 depletion results in impaired proliferation, migration and invasion, and in enhanced apoptosis.…”

Section: Sumo Proteases In Cancermentioning

confidence: 99%

“…Database analysis indicates that in general SENP3 is abundantly expressed in sarcoma and high expression correlates with poor prognosis, being shown in osteosarcoma that SENP3 depletion results in impaired proliferation, migration and invasion, and in enhanced apoptosis. Thus, SENP3 has been suggested as a powerful biomarker for osteosarcoma diagnosis [ 122 ]. SENP3 , in combination with ARID1A and CSMD has also been proposed as an effective prognosis marker in HCC, despite molecular heterogeneity detected in HCC patients [ 118 ].…”

Section: Sumo Proteases In Cancermentioning

confidence: 99%

Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases

Lara-Ureña

Jafari

García‐Domínguez

2022

IJMS

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SUMOylation is a post-translational modification that has emerged in recent decades as a mechanism involved in controlling diverse physiological processes and that is essential in vertebrates. The SUMO pathway is regulated by several enzymes, proteases and ligases being the main actors involved in the control of sumoylation of specific targets. Dysregulation of the expression, localization and function of these enzymes produces physiological changes that can lead to the appearance of different types of cancer, depending on the enzymes and target proteins involved. Among the most studied proteases and ligases, those of the SENP and PIAS families stand out, respectively. While the proteases involved in this pathway have specific SUMO activity, the ligases may have additional functions unrelated to sumoylation, which makes it more difficult to study their SUMO-associated role in cancer process. In this review we update the knowledge and advances in relation to the impact of dysregulation of SUMO proteases and ligases in cancer initiation and progression.

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“…Many studies have reported findings related to DNA methylation in OS. According to reports, overexpression of SENP3 can increase DNA methylation of E-Cad and then increase the proliferation, migration and invasion of osteosarcoma cells ( Yang et al, 2020 ). The high expression level of WNT6 in primary osteosarcoma is mainly due to the low DNA methylation level of WNT6, while the DNA methylation of WNT6 shows a negative correlation with the prognosis of children with osteosarcoma ( Li et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Integral Analyses of Competing Endogenous RNA Mechanisms and DNA Methylation Reveal Regulatory Mechanisms in Osteosarcoma

Wei

Lin

et al. 2021

Front. Cell Dev. Biol.

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Background: Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents, with rapid growth, frequent metastasis, and a poor prognosis, but its pathogenesis has not been fully elucidated. Exploring the pathogenesis of OS is of great significance for improving diagnoses and finding new therapeutic targets.Methods: Differentially expressed circRNAs (DECs), miRNAs (DEMs), methylated DNA sites (DMSs), and mRNAs (DEGs) were identified between OS and control cell lines. GSEA of DEGs and functional enrichment analysis of methylated DEGs were carried out to further identify potential biological processes. Online tools were used to predict the miRNA binding sites of DECs and the mRNA binding sites of DEMs, and then construct a circRNA-miRNA-mRNA network. Next, an analysis of the interaction between methylated DEGs was performed with a protein-protein interaction (PPI) network, and hub gene identification and survival analysis were carried out. The expression pattern of circRNA-miRNA-mRNA was validated by real-time PCR.Results: GSEA and functional enrichment analysis indicated that DEGs and methylated DEGs are involved in important biological processes in cancer. Hsa_circ_0001753/has_miR_760/CD74 network was constructed and validated in cell lines. Low expression levels of CD74 are associated with poor overall survival times and show good diagnostic ability.Conclusion: Methylated DEGs may be involved in the development of OS, and the hsa_circ_0001753/has_miR_760/CD74 network may serve as a target for the early diagnosis of and targeted therapy for OS.

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High SENP3 Expression Promotes Cell Migration, Invasion, and Proliferation by Modulating DNA Methylation of E-Cadherin in Osteosarcoma

Cited by 6 publications

References 43 publications

SENP3 promotes tumor progression and is a novel prognostic biomarker in triple-negative breast cancer

SENP3 promotes tumor progression and is a novel prognostic biomarker in triple-negative breast cancer

Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases

Integral Analyses of Competing Endogenous RNA Mechanisms and DNA Methylation Reveal Regulatory Mechanisms in Osteosarcoma

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