​​​​​​Aging-US: Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells

Aging-US published a Special Collection on Eye Disease which included "Loss of macroH2A1 decreases mitochondrial metabolism and reduces the aggressiveness of uveal melanoma cells" which reported that uveal melanoma (UM) is the most common primary intraocular tumour in adults.

Most accurate prognostic factor of UM is classification by gene expression profiling. These authors recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.

Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach

Dr. Giovanni Li Volti and Dr. Manlio Vinciguerra said, "Uveal melanoma (UM) is the most common primary intraocular tumour in adults."

Metastasis is a frequent occurrence in uveal and cutaneous melanomas with a 5 years survival of 15%. By far the most common site of UM metastasis is the liver, reported in 87% of cases.

Epigenetic mechanisms controlling gene expression have long been known to have a role in cancer development. In UM these include DNA methylation at CpG islands leading to decrease expression of p16/INK4a tumour suppressor protein.

Figure 7. COX4|1 mRNA expression levels correlate with the surviving rate in UM metastatic patients. Correlation analysis of COX4|1 with surviving rate in (A) 88 metastatic (M-UM) and 102 (B) non-metastatic (not-M-UM) UM patients. Data are expressed as z-score intensity expression levels and presented as vertical scatter dot plots. Correlations were determined using Pearson’s ρ correlation. P values <0.05 were considered to be statistically significant (*p<0.05; **p<0.005;***p<0.0005; ****p<0.00005).

The Volti/Vinciguerra Research Team concluded in their Aging-US Research Output, "we suggest that strategies aiming at decreasing the expression of histone variant macroH2A1 [32], might effectively hamper the aggressiveness of UM cells, by inhibiting their mitochondrial phosphorylation. This could be a novel promising therapeutic strategy against UM [51]."

Full Text - https://www.aging-us.com/article/103241/text

Correspondence to: Giovanni Li Volti email: livolti@unict.it and Manlio Vinciguerra email: manlio.vinciguerra@fnusa.cz

Keywords: macroH2A1, histones, uveal melanoma, metabolism, epigenetics