AURKA Overexpression Is Driven by FOXM1 and MAPK/ERK Activation in Melanoma Cells Harboring BRAF or NRAS Mutations: Impact on Melanoma Prognosis and Therapy

Puig-Butillé, Joan Antón; Vinyals, Antònia; Ferreres, J.R.; Aguilera, Paula; Cabré, Eduard; Tell‐Martí, Gemma; Marcoval, Joaquim; Mateo, Francesca; Palomero, Luís; Badenas, Cèlia; Piulats, Josep María; Malvehy, Josep; Pujana, Miquel Àngel; Puig, Susana; Fabra, Àngels

doi:10.1016/j.jid.2017.01.021

Cited by 48 publications

(45 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although Vemurafenib rapidly improves the symptoms of melanoma patients, most patients acquire symptoms of drug resistance after 6-7 months [ 41 – 43 ]. Similar drug resistance has also been found in patients treated with an ERK inhibitor [ 44 ] or MEK inhibitor [ 45 ]. The occurrence of drug resistance in melanoma treatment has been found to be associated with multiple mechanisms, including secondary mutations, target gene mutations, changes in drug metabolism, and the activation of compensatory pathways [ 41 ].…”

Section: Discussionsupporting

confidence: 61%

RTL1 promotes melanoma proliferation by regulating Wnt/β-catenin signalling

Fan

Ye²,

Zhu³

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Cutaneous melanoma is a highly malignant and metastatic skin cancer with high mortality. However, its underlying mechanisms remain largely unclear. Here, we found that retrotransposon-like 1 (RTL1) is highly enriched in melanoma tissue, especially in early and horizontal growth tissues. Knockdown of RTL1 in melanoma cells resulted in cell proliferation suppression; cell cycle arrest at G1 phase; and down-regulation of E2F1, CYCLIN D1, cyclin-dependent kinase 6 (CDK6) and c-MYC. Moreover, overexpression of RTL1 in melanoma cells accelerated cell proliferation, promoted passage of the cell cycle beyond G1 phase, and increased the expression of cell cycle related genes. Mechanistically, we found that knockdown of RTL1 inhibited the Wnt/β-Catenin pathway by regulating the expression of genes specifically involved in β-CATENIN stabilization. Furthermore, the overexpression and knockdown of β-CATENIN rescued the effects of RTL1 on melanoma cell proliferation and the cell cycle. These findings were also confirmed via tumour xenografts in nude mice. Together, our results demonstrated that RTL1 promotes melanoma cell proliferation by regulating the Wnt/β-Catenin signalling pathway.

show abstract

Section: Discussionsupporting

confidence: 61%

RTL1 promotes melanoma proliferation by regulating Wnt/β-catenin signalling

Fan

Ye²,

Zhu³

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…In our study, FOXM1 was upregulated in tumor tissues compared to normal tissues, suggesting a signi cant correlation with melanoma. Previous studies have shown that higher levels of FOXM1 in tumor tissues have been strongly associated with poor prognosis in melanoma patients, consistent with our study [33][34][35]. Kinesin Family Member 20A (KIF20A) is also a proteinencoding gene, and what is known about the diseases associated with this gene is mainly familial restriction Familial Isolated Restrictive Cardiomyopathy and Charcot-Marie-Tooth Disease, Type 4C.…”

Section: Discussionsupporting

confidence: 91%

Identification of Hub Genes Associated with Melanoma Development by Comprehensive Bioinformatics Analysis

Jiang

Liang

et al. 2020

Preprint

View full text Add to dashboard Cite

Introduction: The aim of this study was to identify important genes associated with melanoma for further development of new target gene therapies and to analyze their significance in relation to prognosis.Materials and methods: Gene expression data for melanoma and normal tissue were downloaded from three databases. Differentially co-expressed genes were identified by WGCNA and DEGs analysis. These genes were subjected to GO and KEGG enrichment analysis as well as construction of the PPI, visualized with Cytoscape, and screened for the top 10 Hub genes using CytoHubba. We verified the protein levels of the Hub gene using the HPA database.Results: A total of 435 differentially co-expressed genes were obtained. Survival curves showed that high expression of FOXM1, EXO1, KIF20A, TPX2 and CDC20 in melanoma patients with 5 of the top 10 hub genes was associated with reduced overall survival (OS). The HPA database results showed that FOXM1, KIF20A, TPX2 and CDC20 showed upregulated expression in melanoma compared to normal tissues.Conclusion: FOXM1, KIF20A, TPX2, and CDC20 are prognosis-associated core genes of melanoma, and their high expression correlates with low prognosis of melanoma patients, and can be used as biomarkers for melanoma diagnosis, treatment, and prognosis prediction.

show abstract

“…AURKA protein kinase plays an important role in the development of malignant tumors. AURKA has been highly expressed in various malignant tumors, such as esophageal cancer, laryngeal cancer, liver cancer, and ovarian cancer [52][53][54]. AURKA may participate in the formation of tumors through two functions.…”

Section: Discussionmentioning

confidence: 99%

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Chu

Liu

et al. 2019

J Transl Med

View full text Add to dashboard Cite

Background: Glioma accounts for a large proportion of cancer, and an effective treatment for this disease is still lacking because of the absence of specific driver molecules. Current challenges in the treatment of glioma are the accurate and timely diagnosis of brain glioma and targeted treatment plans. To investigate the diagnostic biomarkers and prospective role of miRNAs in the tumorigenesis and progression of glioma, we analyzed the expression of miRNAs and key genes in glioma based on The Cancer Genome Atlas database. Methods: Of the 701 cases that were downloaded, five were normal and 696 were glioma. Then, 1626 differentially expressed genes were identified, and 173 aberrantly expressed miRNAs were calculated by edgeR. GO and KEGG pathway enrichment analyses were performed using Cytoscape software. A coexpression network was built by weighted correlation network analysis (WGCNA). A cell scratch test and transwell, cell apoptosis and cell cycle assays were performed to validate the function of hsa-let-7b-5p. Results: Based on crosstalk genes in the KEGG, PPI network, and WGCNA analyses, PLK1, CCNA2, cyclin B2 (CCNB2), and AURKA were screened as candidate diagnostic marker genes. The survival analysis revealed that high mRNA expression of PLK1, CCNA2, and AURKA was significantly associated with poor overall survival. Furthermore, hsalet-7b-5p was identified as a core miRNA in the regulation of candidate genes involved in glioma development. We confirmed that hsa-let-7b-5p could inhibit the migration, invasion, and cell cycle of glioma cells. Conclusions: This study provides four potential biomarkers for the diagnosis of glioma, offers a potential explanation of its pathogenesis, and proposes hsa-let-7b-5p as a therapeutic target.

show abstract

AURKA Overexpression Is Driven by FOXM1 and MAPK/ERK Activation in Melanoma Cells Harboring BRAF or NRAS Mutations: Impact on Melanoma Prognosis and Therapy

Cited by 48 publications

References 48 publications

RTL1 promotes melanoma proliferation by regulating Wnt/β-catenin signalling

RTL1 promotes melanoma proliferation by regulating Wnt/β-catenin signalling

Identification of Hub Genes Associated with Melanoma Development by Comprehensive Bioinformatics Analysis

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Contact Info

Product

Resources

About