Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells.

Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells. Aging (Albany NY). 2020 May 12;12: Authors: Giallongo S, Di Rosa M, Caltabiano R, Longhitano L, Reibaldi M, Distefano A, Lo Re O, Amorini AM, Puzzo L, Salvatorelli L, Palmucci S, Tibullo D, Russo A, Longo A, Lazzarino G, Li Volti G, Vinciguerra M Abstract Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.MacroH2A1 loss significantly attenuated UM cells proliferation and aggressiveness. Furthermore, genes involved in oxidative phosphorylation displayed a decreased expression in KD cells. Consistently, macroH2A1 loss resulted also in a significant decrease of mitochondrial transcription factor A (TFAM) expression, suggesting impaired mitochondrial replication. ...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research

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Malignant melanoma is the most deadly form of skin cancer. It originates from melanocytic cells and can also arise at other body sites. Early diagnosis and appropriate medical care offer excellent prognosis with up to 5-year survival rate in more than 95% of all patients. However, long-term survival rate for metastatic melanoma patients remains at only 5%. Indeed, malignant melanoma is known for its notorious resistance to most current therapies and is characterized by both genetic and epigenetic alterations. In cutaneous melanoma (CM), genetic alterations have been implicated in drug resistance, yet the main cause of this...
Source: Theranostics - Category: Molecular Biology Authors: Tags: Review Source Type: research
Conclusions: The infiltration of immune cells in 32 cancer types was quantified, and considerable heterogeneity was observed in the prognostic relevance of these cells in different cancer types. An ICCS model was constructed for LUAD with competent prognostic performance, which can further deepen our understanding of the TME of LUAD and can have implications for immunotherapy.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It has been demonstrated that microRNA-145 (miR-145) is correlated with the progression of various cancers by regulating the expression of multiple target genes, especially a number of genes that regulate angiogenesis and proliferation. However, the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated. Thus, we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis. METHODS: Totally, 24 ch...
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
In unpublished studies, we recently found that a cyclin-dependent kinase 9 (CDK9) degrader (Thal-SNS-032, TS-032) selectively inhibited BRAF/NRAS wild type melanomas. We now confirm this finding using another competitive CDK9 inhibitor, NVP-2. To further explore the context of this vulnerability, we undertook a large RNA seq analysis of 9 pigment cell lines (1 triple wild-type melanoma line, 2 uveal lines, 2 BRAF-mutated, 2 NRAS-mutated, 1 NF1-mutated, and 1 immortalized melanocyte line) in order to uncover transcriptional programs which may be preferentially extinguished or activated by TS-032 and NVP-2.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
The purpose of this study is to systematically review the safety and efficacy of carbon ‐ion radiotherapy (CIRT) for malignant melanoma. Eleven studies were eligible. For overall survival, cutaneous melanoma, and uveal melanoma had a slight advantage than mucosal melanoma. Concurrent CIRT with chemotherapy exhibited superior PFS than CIRT alone. Younger patients presented a higher di stant metastasis for gynecological melanoma. Although available data demonstrated that malignant melanoma is effectively and safely treated with CIRT, it is suitable to organically combine systemic therapy to obtain the best prognosis for me...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: REVIEW Source Type: research
Authors: Zhang Z, Ni Y, Chen G, Wei Y, Peng M, Zhang S Abstract Uveal melanoma (UM) is the most frequent primary ocular tumour among adults. Here, we aimed to establish the immune cell-based signature to predict the overall survival (OS) of UM patients. The mRNA profile and matched clinical records of 80 UM patients were downloaded from The Cancer Genome Atlas (TCGA) database. CIBERSORT was used to verify the immune cell types of individuals. The univariate analysis found the CD8+ T cell, monocyte, CD4+ memory T cell (resting) and mast cell (resting) were significantly associated with the OS of UM patients. Subsequ...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
Abstract Immunotherapy has recently become a powerful weapon against cancer. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) was the first immune checkpoint used for immunotherapy. However, CTLA-4-related mechanisms in various cancers have not been comprehensively investigated. This aim of this study was an in-depth investigation of CTLA-4 in the tumor microenvironment and its relationship with other immunomodulators, immune-related pathways and survival outcomes of 33 cancer types. Overall 9,743 tumor samples and 710 normal samples of 33 cancer types from The Cancer Genome Atlas (TCGA) database were included...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
Queirolo Rosaria Gangemi Uveal melanoma (UM) is a rare tumor of the eye that leads to deadly metastases in about half of the patients. ADAM10 correlates with c-Met expression in UM and high levels of both molecules are related to the development of metastases. MiR122 and miR144 modulate ADAM10 and c-Met expression in different settings. We hypothesized a potential onco-suppressive role for miR122 and miR144 through modulation of ADAM10 and c-Met in UM. We analyzed the UM Cancer Genome Atlas data portal (TCGA) dataset, two other cohorts of primary tumors and five human UM cell lines for miR122 and miR144 expression b...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Uveal melanoma (UM) is the most common intraocular malignancy. The incidence of UM is 10 cases per million per year in New Zealand (twice the US incidence). Treatment options include enucleation, plaque brachytherapy and localised radiotherapy. Despite successful treatment of the primary tumour, metastasis occurs in up to half of all patients.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
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