Role of the long non-coding RNA PVT1 in cancer

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Abstract Here we propose that a long non-coding RNA PVT1 can provide a solution for developing effective therapy against multiple human cancers. We have recently identified the mechanistic basis of 8q24 amplification, one of the most common mutations present in almost all kinds of cancer. We have identified a long noncoding RNA, PVT1, which is a part of the 8q24 amplicon, as a major oncogene. We have found that PVT1 can regulate the stability of MYC, one of the most important drivers in cancer. We hypothesize that the dependence of MYC on PVT1 can be exploited to target MYC, otherwise a notoriously undruggable candidate. In this proposal we propose to dissect the mechanism through which PVT1 regulates MYC protein levels in cancer. We also investigate the role of PVT1 in cancers without supernumerary 8q4. Finally, we will examine the therapeutic potential of PVT1 specific antisense oligonucleotides in vivo and in xenograft models. We propose that our new findings will enable the cancer community to develop new therapeutic strategies for cancer patients in near future.