Background:
SWI/SNF chromatin remodelling complex is altered in nearly 20% of all human tumor types, which places it as the most broadly
mutated molecular system in human cancer, just after TP53 [1, 2]. Nevertheless, the molecular mechanisms through which these
alterations foster cancer development remain to be fully understood. In addition, any potential susceptibility associated with
SWI/SNF alterations might be exploited for the treatment of patients affected by different malignancies.
Methodology:
We have generated stably-transduced cell lines for a doxycycline-inducible vector that directs the expression of different shRNAs
targeting ARID1A, ARID1B or ARID2 in different human cancer cell lines. We have studied the transcriptional alterations resulted
from the deficiency of these subunits in different cellular contexts by RNA-Seq, as well as the changes in chromatin accessibility
by ATAC-Seq. Additionally, we have studied the sensitivity of these cell lines to different antitumoral treatments.
Results:
We have identified molecular pathways differently expressed in the SWI/SNF-deficient cell lines that might explain some
characteristics of the behaviour of these tumor cells. Thus, we have seen an overexpression of genes involved in ROS production,
as well as genes encoding metallopeptidases, and a downregulation of genes related to cellular adhesion or tumor suppression.
Finally, we have detected different sensitivities in the ARID-deficient cells to some treatments, like cis-platin, and PARP or EGFR
inhibitors.
