Sci Adv: ARID1A deficiency promotes epinephrine-interstitial transformation of neuroblastoma cells.

15% of the total number of deaths from !---- 1.MYCN gene amplification (MYCN amplification) is the most common genetic abnormality of neuroblastoma and is positively correlated with advanced disease (mostly stage 3 or 4) and adverse prognosis2.myCN gene amplification of neuroblastomas are often accompanied by chromosomal 1p36 heterogeneous deficiency, and ARID1A is also distributed in this region as the sub-base of the SWI/SNF chromatin retinive complex (chromatin-remodeling complexes) in malignant tumors.according to the transcription factor expression network of super-enhanced sub-couples, neuroblastoma cells can be divided into two different lineages, epinephrine energy (ADRN) cells and mecemic (MES) cells, which can transform each other under certain conditions3.MES cells are more resistant and migrate than ADRN cells., Science Advances published an online report on the Dana-Farber Cancer Institute at Harvard Medical School. The results of Professor Thomas Look's team (Dr. Shi Hui and Dr. Tao Ting are co-authors of the article): ARID1A ross in neuroblastoma promots the adrenergic-to mesenchymal transition by regulating fod-mediated gene gene.study reveals arid1A's regulation and transformation of neuroblastoma.ARID1A has two homologous genes in zebrafish, arid1aa and arid1ab.the authors found that the absence of only one copy of arid1aa or arid1ab could promote the occurrence and progression of MYCN-induced zebrafish neuroblastoma, suggesting that ARID1A is a haploid deficiency tumor suppressor gene in MYCN-induced neuroblastoma., the authors then conducted further work on the mechanism of the NGP neuroblastoma cell line in which the MYCN gene amplification but the ARID1A gene was not found to be missing or mutated.studies have found that in neuroblastoma cells, the absence of function of ARID1A can change the distribution of BAF and PBAF chromatin remodeling complex on the enhancer, which in turn regulates the activity of the enhancer and alters the level of gene expression.more interesting, they found that the enhancer signal of the PHOX2B gene weakened significantly in the cells missing from ARID1A, and the corresponding RNA and protein expression nearly disappeared.in contrast, the enhancer signal of the FN1 gene increases significantly in cells missing from ARID1A, and RNA and protein expression increase significantly.phoX2B is a characteristic transcription factor for ADRN cells, and FN1 is an important signature gene for MES cells.this means that ARID1A may play an important role in the cell state transition of neuroblastoma.gene enrichment analysis also shows that ARID1A missing cells have a tendency to convert to MES cells.they also confirmed that ARID1A-defective cells have higher resistance to general chemotherapy drugs (cisplatin) and greater migration. concluded that the absence of ARID1A led to changes in the distribution of BAF and PBAF complexes in enhancers, which in turn regulated the activity of the enhanced daughter and altered gene expression levels, further leading to the transformation of neuroblastoma cells from ADRN cells to MES cells, resulting in greater migration and resistance. in addition, the missing neuroblastoma model of zebrafish arid1a and arid1ab in this study could be further used as screening for neuroblastoma drugs for the absence of aRID1A in humans. .