AI Article Synopsis
- - The study found that cancer cells surviving from a specific treatment (ALA-PDT) had abnormal mitochondria and reduced ability to invade other cells.
- - Increased levels of histone deacetylase (HDAC) in these cells led to changes in gene expression, decreasing the activity of invasion-related genes like MMP9 and PEG1.
- - The research suggests that dysfunctional mitochondria can influence the invasiveness of cancer cells by activating HDAC, which modifies histones and affects the expression of certain genes.
Article Abstract
Previously, we have found that cancer cells survived from 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) have abnormal mitochondrial function and suppressed cellular invasiveness. Here we report that both the mRNA expression level and enzymatic activity of histone deacetylase (HDAC) were elevated in the PDT-derived variants with dysfunctional mitochondria. The activated HDAC deacetylated histone H3 and further resulted in the reduced migration and invasion, which correlated with the reduced expression of the invasion-related genes, matrix metalloproteinase 9 (MMP9), paternally expressed gene 1 (PEG1), and miR-355, the intronic miRNA. Using chromatin immunoprecipitation, we further demonstrate the reduced amount of acetylated histone H3 on the promoter regions of MMP9 and PEG1, supporting the down-regulation of these two genes in PDT-derived variants. These results indicate that HDAC activation induced by mitochondrial dysfunction could modulate the cellular invasiveness and its related gene expression. This argument was further verified in the 51-10 cybrid cells with the 4977 bp mtDNA deletion and A375 ρ⁰ cells with depleted mitochondria. These results indicate that mitochondrial dysfunction might suppress tumor invasion through modulating histone acetylation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632734 | PMC |
| http://dx.doi.org/10.3390/ijms161023994 | DOI Listing |
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