Decoding the Role of the Long Non-Coding RNA PVT1 in Medulloblastoma

Pediatric Cancer

Anindya Bagchi (SBP)

Lukas Chavez (UCSD)

Medulloblastoma is the most common malignant childhood brain tumor. It is a highly heterogeneous cancer, comprising four subgroups: Sonic Hedgehog, Wingless, Group 3, and Group 4. Group 3 MB has the worst prognosis of all Medulloblastomas. Group 3 often exhibits amplification of chromosome 8q24, which contains the potent oncogene MYC. Unfortunately, patients with MYC-driven MB have few therapeutic options, since MYC is extremely refractile as a drug target. We have previously uncovered an important sensitizer of MYC, in form of PVT1. Inhibition of PVT1 effectively eliminates MYC protein, which in turn inhibits tumor growth. We have recently discovered that the critical unit in PVT1 is a 104 aa peptide, which we call Firefox (FFX), which augments MYC protein in cells. Here we propose to investigate the molecular mechanisms by which FFX controls MYC expression, and to design ways to target FFX which can, in turn, reduce MYC, and inhibit the cancer in these patients. This will uncover a novel way for new therapies for MYC driven MB patients