PARP inhibition offsets LMP1-mediated gene activation.

A) Expression of 292 genes were significantly changed (FDR2 I1I Fold Change) when comparing LMP1- vs LMP1+ cells and overlaying this dataset with LMP1+ untreated cells vs LMP1+ cells treated with 1 μM olaparib for 72 hrs. B) Of these 292 genes, the majority (225) were upregulated by LMP1, which was offset by PARP inhibition. C) Heat map showing two gene clusters- cluster 1 genes are those upregulated by LMP1 and subsequently downregulated following PARP1 inhibition, and cluster 2 genes are those downregulated by LMP1 and subsequently upregulated following PARP1 inhibition. Gene expression is plotted as z-score normalized FPKM values. D) Ingenuity Pathway Analysis, IPA, reveals the gene functions of the PARP1/LMP1 targets are largely involved in metabolism and signaling. E) IPA Disease or function analysis identifies cancer, proliferation of lymphatic system and proliferation of lymphocytes as being LMP1/PARP1 targets that are decreased following olaparib treatment. F) IPA identified HIF-1α as a top upstream regulator activated by LMP1/PARP1 and inhibited following PARP inhibition.