Transcriptome profiling of B-cell lymphoma cells with pharmacological inhibition of KDM5A/B by using the inhibitor JQKD82

Histone methylation critically controls the progression of human diseases, including infections and cancers. Our study reported that histone lysine demethylases (KDMs) in the KDM5 family KDM5A/B play profound roles in suppressing lytic reactivation of oncogenic human herpesvirus 8 (HHV-8), i.e., Kaposi's sarcoma-associated herpesvirus (KSHV), a human gamma-herpesvirus and an etiological agent of multiple malignancies. During KSHV lytic reactivation from latency, host innate immune responses are also activated, which is expected to favor the tumor cell killing by generating the additional oncolytic effects. To further study the systemic effect of KSHV on host immune response under the regulation of KDM5A/B, we performed the transcriptome profiling analysis for both KSHV-infected BCBL-1 vs KSHV-negative BJAB cells with or without JQKD82 treatment by RNA-seq. Our RNA-seq analysis and further experimental validation suggested that the KDM5 inhibitor JQKD82 is capable of inducing antiviral/antitumor innate immune responses in KSHV-negative B-cell lymphomas, but such effects are more striking in KSHV-positive B-cell lymphomas likely due to KSHV lytic reactivation that further triggers the innate immune activation in tumor cells.