ABSTRACT :
Lung cancer is the most common cancer as well as the first cause of cancer related deaths in the world.
In this context, any new knowledge on the molecular mechanisms that are involved in lung cancer
development are of great interest to improve patient treatment.
Many tumor types, also including lung cancer, present recurrent mutations in SWI/SNF chromatin
remodeling genes although, the molecular pathways affected by these defects and how to exploit them
for lung cancer treatment are largely unknown.
In this project, we have characterized different lung cancer cellular models knock-down for the most
recurrently altered SWI-SNF subunits (ARID1A, ARID2 and SMARCA4). We have demonstrated that,
in most of the cases, the selected shRNA, used to silence the target genes, is effective in downregulating
the different subunits. Furthermore, we have compared different strategies to extract RNA from these
models to perform ultra-sequencing libraries. Finally, we have performed ATAC-seq and RNA-seq in
these cellular models to identify changes in chromatin structure and the consequent associated gene
expression changes.
The identification of the molecular pathways directly regulated by SWI/SNF complex could open new
lines of research and be translated to improve treatments for lung cancer patients.
