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PARP1 inhibition counteracts EBV+ lymphoma progression through EBNA2/MYC axe

ABSTRACT: Our group has previously identified how PARP1 can control EBV latency by: (1) altering the 3D virus chromatin structure [28]; (2) regulating CTCF binding on EBV promoters and supporting the latency expression program [29-32]; (3) repressing the lytic gene expression by binding BZLF1 promoter [33, 34]. To date, the therapeutic effect of PARP1 inhibitors on EBV+ lymphomagenesis has been poorly explored. Therefore, we aimed to investigate whether PARP1i was able to counteract EBV-driven tumors in a LCL xenograft model and identify, and confirm, possible mechanisms underlying its therapeutic effect. In the present study we demonstrate that PARP1 inhibition restricts EBV-driven lymphoma in vivo, pointing out the oncogene MYC as its functional target. Specifically, PARP1 inhibition reverts the tumor growth and the metastatic potential of EBV+ LCL, inducing a dramatic transcriptional reprogramming. Interestingly, the absence of PARP1 activity causes a decrease in MYC expression, subsequently leading to a dysregulation of MYC-associated co-factors and targets, both in vivo and in vitro. Our findings also corroborate the link between PARP1 and EBNA2 expression, that we previously demonstrated in vitro. Overall, our study strengthens the central role of PARP1 in EBV malignant transformation and outlines the EBNA2/MYC pathway as an additional target of PARP1 regulation in LCL

ORGANISM(S): Mus musculus

PROVIDER: GSE236050 | GEO | 2024/06/27

REPOSITORIES: GEO

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