RNA-seq analysis of CNE1 cells based on LMP1 expression

Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection are the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism remains unclear. Here, we found DNA tumor viruses, such as EBV and HPV, inhibited antioxidant activity and increased oxidative stress of tumor through analyzing RNA-seq data of clinical samples. Further, we found the oncoproteins of DNA tumor viruses, such as LMP1 of EBV and E7 of HPV, interacted with PERK through a conserved motif, which inhibited PERK-Nrf2 signaling and increased the level of reactive oxygen species (ROS). This inhibition of PERK-Nrf2 signaling in LMP1- or E7- positive cancer cells exhibited an increased sensitivity to chemotherapy in vivo. Meanwhile, LMP1- or E7-induced ROS promoted tumor growth. Consistently, disruption of viral oncoprotein-PERK interactions attenuated tumor growth and efficacy of chemotherapy in tumor-bearing mouse models. Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK-Nrf2 signaling might be an attractive strategy for the treatment of NPC and cervical carcinoma. Overall design: mRNA profiles of CNE1 cells stably expressing LMP1