MDA-MB-231 gene expression upon IRE1 RNase inhibition with MKC-8866

The IRE1 Rnase domain has been implicated in the pathology of triple negative breast cancer (TNBC), a disease with limited treatment options. The IRE1 Rnase mediates it's effects on the transcriptome via activation of the trancription factor XBP1s and via direct cleavage of mRNA through a process called RIDD. The processes through which the RNase domain contributes to TNBC is not fully understood. We used a novel small molecule inhibitor of the IRE1 Rnase to find novel targets of IRE1 in TNBC, in an effort to elucidate how it contributes to the disease. A TNBC cell line MDA-MB 231 was treated with the IRE1 Rnase inhibitor for 4, and 24h in normoxic and hypoxic (1% O2) conditions. We aimed to determine effects of inhibiting IRE1 on an early and a later timepoint to have a broader uderstand how IRE1 Rnase effects cells. Recent reports suggest that XBP1s plays a role in controlling the hypoxic stress response in TNBC cells. To find novel hypoxia-specific functions for IRE1 we inhibited the RNase under hypoxic condditions.