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Role of the Long Non-coding RNA PVT1 in Cancer

长非编码 RNA PVT1 在癌症中的作用

基本信息

批准号：
9464456
负责人：
Anindya Bagchi
金额：
$ 44.61万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9464456
关键词：
8q24 Ablation Advanced Malignant Neoplasm Affect Alleles American American Cancer Society Antisense Oligonucleotides Attenuated Biochemical Bioinformatics Biological Assay Breast CRISPR/Cas technology Cancer Intervention Cancer Patient Cell Line Cell Nucleus Cessation of life Colorectal Colorectal Cancer Communities Complex Data Databases Dependence Development Diagnosis Discipline Disease Effectiveness Family Fatty acid glycerol esters Feedback Future Genes Genetic Techniques Goals Health Human Intestines Lead Life Malignant - descriptor Malignant Neoplasms Mammary Neoplasms Mammary gland Measures Mediating Molecular Mouse Mammary Tumor Virus Mus Mutation Oncogenes Oncogenic Outcome Pharmaceutical Preparations Pharmacologic Substance Phosphorylation Plasmacytoma Play Proteins RNA Splicing Regulation Ribonucleoproteins Role Societies Testing The Cancer Genome Atlas Therapeutic Therapeutic Intervention Transplantation Tumorigenicity Untranslated RNA Variant Work Xenograft Model Xenograft procedure adenoma cancer cell cancer therapy drug candidate effective therapy in vivo insight malignant breast neoplasm metaplastic cell transformation neoplastic cell novel novel therapeutic intervention small molecule targeted treatment therapy development transcriptome sequencing tumor tumor growth tumorigenesis tumorigenic villin

项目摘要

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.

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，开发有效的治疗方法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