Effect of p53 on the expression of combo induced dsRNAs in 2153L GEM tumors
We analyzed the expression of dsRNAs in control and p53 restored 2153L GEM tumors upon different treatments. Our ChIP-seq and RNA-seq experiments showed that the restored p53 bound to the regulatory regions of dsRNA-containing genes that account for 91% of the total dsRNA abundance in combination therapy–treated 2153L tumors, and suppressed their expression upon combination therapy. The abundance of dsRNA (TPM) was calculated from the dsRIP experiment. Overall design: 2153L GEM tumors were transduced with empty vector control or tamoxifen inducible p53ERTAM. These tumors were further treated with vehicle control or IRE1? RNase inhibitor ORIN1001 (150 mg/kg, daily) and docetaxel (20 mg/kg, weekly) for 8 days. RNA from these tumors was subjected to RNAseq. The dsRNAs-containing genes whose regulatory regions have p53 binding were flited out first, followed by a second selection for genes that upregulated upon combination compared to vehicle in empty vector control transduced tumors. The expression (TPM) of these genes in p53 restored tumors under vehicle or combination therapy was analyzed.