Role of the long non-coding RNA PVT1 in cancer

摘要 在这里，我们提出，一个长的非编码RNA PVT1可以提供一个解决方案，开发有效的治疗 对抗多种人类癌症我们最近已经确定了8q24扩增的机制基础， 几乎所有癌症中最常见的突变。我们发现了一个很长的非编码 RNA，PVT1，是8q24扩增子的一部分，作为主要癌基因。我们已经发现PVT1可以 调节MYC的稳定性，MYC是癌症中最重要的驱动因素之一。我们假设依赖性 可以利用PVT1上MYC的基因来靶向MYC，否则MYC是一个臭名昭著的不可治疗的候选者。在这 我们建议剖析PVT1调节癌症中MYC蛋白水平的机制。 我们还研究了PVT1在没有多余8q4的癌症中的作用。最后，我们将研究 PVT1特异性反义寡核苷酸在体内和异种移植模型中的治疗潜力。我们提出 我们的新发现将使癌症社区能够开发新的癌症治疗策略， 患者在不久的将来

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.