Expression inactivation of SMARCA4 by microRNAs in lung tumors
SMARCA4 is the catalytic subunit of the SWI/SNF chromatin-remodeling complex, which alters the interactions between DNA and histones and modifies the availability of the DNA for transcription. The latest deep sequencing of tumor genomes has reinforced the important and ubiquitous tumor suppressor role of the SWI/SNF complex in cancer. However, although SWI/SNF complex plays a key role in gene expression, the regulation of this complex itself is poorly understood. Significantly, an understanding of the regulation of SMARCA4 expression has gained in importance due to recent proposals incorporating it in therapeutic strategies that use synthetic lethal interactions between SMARCA4-MAX and SMAR…
Abstract 4479: Unveiling the relationship between the SWI/SNF chromatin remodeling complex and noncoding RNAs
Abstract Chromatin remodeling complexes are crucial for the viability of the cells due to their role in regulating interactions between DNA and histones and, therefore, modifying the accessibility of the genetic information to the transcriptional machinery. This relevance can also been seen in the SWI/SNF complex that has been associated with cancer in the last deep-sequencing efforts on tumoral genomes. BRG1 is the helicase/ATPase catalytic subunit of the SWI/SNF complex and it is frequently lost in NSCLC cell lines with a high mutation rate. In primary tumors, the loss of expression of BRG1 is also frequent, however it cannot be explained by mutations or by promoter hypermethylation. In t…
Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models
Simple Summary: Mammalian SWI/SNF complexes regulate gene expression by reorganizing the way DNA is packaged into chromatin. SWI/SNF subunits are recurrently altered in tumors at multiple levels, including DNA mutations as well as alteration of the levels of RNA and protein. Cancer cell lines are often used to study SWI/SNF function, but their patterns of SWI/SNF alterations can be complex. Here, we present a comprehensive characterization of DNA mutations and RNA and protein expression of SWI/SNF members in 38 lung adenocarcinoma (LUAD) cell lines. We show that over 85% of our cell lines harbored at least one alteration in one SWI/SNF subunit. In addition, over 75% of our cell lines lacked…
BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.
Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromat…