Effects of ACSS2 deficiency on transcriptomic profiling in BE(2)-C neuroblastoma cells

Tumorigenesis also relies on the reprogramming of cellular metabolism, which greatly influences epigenetic and transcriptomic regulation. Specifically, the metabolite acetate serves as an important bioenergetic fuel and a precursor of acetyl-CoA, the substrate for histone acetylation. The enzyme ACSS2, responsible for converting acetate to acetyl-CoA in the cytosol and nucleus, has been associated with substantial reductions in tumor burden in various types of cancer. Our reports have shown that ACSS2 is highly expressed in neuroblastoma, and its expression level is usually associated with unfavorable clinical outcomes and poor survival. In this study, to further elucidate the underlying mechanism that ACSS2 overexpression regulates neuroblastoma tumorigenesis, we performed RNA-seq to examine the transcriptome alternation in neuroblastoma. We discovered that increased MYCN expression in human NB tumors correlates with elevated ACSS2 expression. Furthermore, we found that ACSS2-mediated biosynthesis of acetyl-CoA in regulating MYCN expression in MYCN-amplified neuroblastoma. Together, These results suggested that ACSS2-mediated biosynthesis of acetyl-CoA may be crucial for MYCN expression and progressive malignancy of neuroblastoma by capturing acetate as a carbon source in the cytosol and nucleus. Comparative gene expression analysis of RNASeq data for BE(2)-C cells (NB_NS) and ACSS2 deficient BE(2)-C cells (NB_siACSS2).