The effect of SATB2, circ3915 on gene expression in arsenic-transformed BEAS2B lung epithelial cells [RNA-seq; SATB2 shRNA]

Thus, it is still unclear if non-genetic mechanisms are sufficient to trigger malignant transformation. Chronic, low-dose exposure to inorganic arsenic is known to cause lung malignancies, yet arsenic at low levels does not induce point mutations.

Arsenic exposure upregulates Special AT-rich binding protein 2 (SATB2), a chromatin organizer that reprograms cell-specific and/or developmentally-sensitive gene networks, along with a SATB2-derived circRNA, circ3915. Here we show circ3915 and SATB2 work together to drive mutant KRAS-like gene expression patterns during arsenic-mediated transformation of BEAS2B cells. Thus, oncogenic pathways can be activated in mammalian cells without pre-disposing mutations in oncogenes or epigenetic regulators.