RNF2 E3 or Not to E3: Dual Roles of RNF2 Overexpression in Melanoma

Black, Joshua C.; Whetstine, Johnathan R.

doi:10.1158/2159-8290.cd-15-1285

Cited by 5 publications

(3 citation statements)

References 10 publications

(25 reference statements)

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“…It is executed through ubiquitin-activating enzymes E1, ubiquitin-conjugating enzyme E2, and ubiquitin ligase E3 [88,89]. According to previous studies, dysregulation of E3 ubiquitin enzymes and impropriety targeting of the proteins by E3 leads to many disorders, such as cancer metastasis, including GC [90][91][92][93]. Thus, blocking the ubiquitin-proteasome pathways administers a novel approach to treating carcinomas [94].…”

Section: Discussionmentioning

confidence: 99%

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach

2023

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Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori–induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori–induced cancer compared with the H. pylori–positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori–induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori–induced GC. However, experimental validation is necessary in the future.

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Section: Discussionmentioning

confidence: 99%

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach

2023

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“…Interestingly, the noncatalytic function of RNF2 also provides important insight to potential therapies. MEK1-dependent phosphorylation of RNF2 leads to the formation of alternative complexes containing the histone demethylase KDM6A and the histone acetyltransferase EP300, which activate downstream target genes such as CCND2 [108].This suggests the possibility of using RNF2 inhibitors in combination with either MEK or EP300 inhibitors to target both tumor growth and metastasis [109].…”

Section: Rnf2mentioning

confidence: 99%

The Emerging Epigenetic Landscape in Melanoma

Rollins¹,

Kim²,

Tsao³

2016

Human Skin Cancer, Potential Biomarkers and Therapeutic Targets

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Melanoma is the deadliest form of skin cancer. The disease is driven by molecular alterations in oncogenic signaling pathways, such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K). Activating mutations in oncogenes, such as BRAF and NRAS, and inactivating mutations in tumor suppressors genes, such as PTEN, promote this disease by altering cellular processes involved in growth, survival, and migration. Therapies targeting critical nodes in these pathways have demonstrated efficacy in clinical trials, but their therapeutic potential has been limited by the rapid onset of drug resistance. Durable therapeutic responses have also been observed in patients receiving immunotherapy. However, this activity appears to be confined to a subset of patients, and combinations with targeted therapies have raised safety concerns. Accumulating evidence strongly suggests that the pathogenesis of melanoma is also shaped by the aberrant activity of epigenetic factors that regulate gene expression through the modification of DNA and chromatin. This chapter provides a comprehensive review of the epigenetic alterations in melanoma and highlights the roles played by specific chromatin regulators during disease progression. We also discuss the clinical utility of both first and second generation epigenetic therapies in the melanoma setting, placing emphasis on the potential to overcome resistance to targeted therapies and to serve as priming agents for immunotherapies.

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“…According to the authors [ 10 ] the effect of the LTBP2 down-regulation was stimulation of the TGFβ signaling pathway which in turn promoted invasiveness of melanoma cells. The same study demonstrated also that RNF2 supports anchorage independent proliferation of melanoma cells through up-regulation of cyclin D2 due to activation of CCND2 gene [ 11 ]. Another noteworthy conclusion of Rai et al [ 10 ] was that the spectrum of genes influenced by RNF2 depends on pre-existing chromatin promoter states of the genes.…”

Section: Introductionmentioning

confidence: 99%

Enhanced intratumoral expression of RNF2 is a favorable prognostic factor for patients with cutaneous melanoma?

et al. 2018

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Recent studies involving melanoma cell lines suggest that enhanced expression of epigenetic regulator RNF2 supports proliferation and promotes metastasis. However, it is not clear to what extent those data apply to disease progression and prognosis for melanoma patients. Therefore the aim of the present study was to assess the prognostic power of RNF2 intratumoral expression by melanoma cells.RNF2 was detected immunohistochemically in standard formalin-fixed paraffin-embedded samples of 9 benign nevi, 60 melanomas and 24 nodal metastases.The lowest percentage of RNF2-positive melanocytes found in nevi was comparable to expression levels in normal skin. The RNF2 expression found in melanomas was significantly higher and it was even more enhanced in metastases. The increased occurrence of RNF2 expressing cells was positively correlated with longer patients’ overall survival. Moreover, a negative correlation was found between intratumoral RNF2 expression and number of generated metastatic lesions.Our data indicate that development of melanoma is associated with significant changes in RNF2 intratumoral expression and imply that at least for some patients the enhancement of the expression levels of RNF2 in both primary and metastatic lesions may be considered a favorable prognostic factor in melanoma.

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RNF2 E3 or Not to E3: Dual Roles of RNF2 Overexpression in Melanoma

Cited by 5 publications

References 10 publications

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach

Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach

The Emerging Epigenetic Landscape in Melanoma

Enhanced intratumoral expression of RNF2 is a favorable prognostic factor for patients with cutaneous melanoma?

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