HULLK, a novel lncRNA that functions as a targetable oncogene in PCa
HULLK,一种新型 lncRNA,可作为 PCa 中的靶向癌基因
基本信息
- 批准号:10198408
- 负责人:
- 金额:$ 41.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:Androgen AntagonistsAndrogensAreaBindingBiological ProcessCWR22Rv1Cancer Cell GrowthCellsComplementComplexCytoplasmDNADataDevelopmentDiseaseDoseElementsFOLH1 geneFailureFoundationsGrowthHormone ResponsiveHormonesIn VitroInterdisciplinary StudyLNCaPLeadLigandsLymphocyte-Specific p56LCK Tyrosine Protein KinaseMalignant NeoplasmsMalignant neoplasm of prostateMass Spectrum AnalysisMediator of activation proteinMessenger RNAMetastatic Prostate CancerMicroRNAsModelingMolecularNamesOncogenesOncogenicPatientsPrognosisPropertyProstate Cancer therapyProteinsPublishingRegulatory ElementRelapseSmall Interfering RNATechniquesTestingTexasThe Cancer Genome AtlasTherapeuticTissuesTranscriptTranslationsTreatment EfficacyUniversitiesUntranslated RNAVCaPVirginiaantigen bindingcancer cellcastration resistant prostate cancercell growthclinically relevantcohortcombatdesigneffective therapyexperimental studyin vitro Modelin vivoin vivo Modelin vivo evaluationinnovationknock-downnanocarriernext generation sequencingnovelnovel strategiesnovel therapeuticsoverexpressionpatient derived xenograft modelprostate cancer cellprostate cancer modelprostate cancer progressionprotein transportresponsesmall hairpin RNAtherapeutic targettumor growthvirtual
项目摘要
Abstract
There remains a critical need for more effective therapies for prostate cancer and for castration resistant prostate
cancer. While localized prostate cancer (PCa) has a favorable prognosis, castration-resistant prostate cancer
(CRPC) remains incurable. The failure of current therapies demonstrates a need for new approaches, and
exposes an incomplete understanding of the underlying mechanisms that drive PCa to CRPC. Long noncoding
RNAs (lncRNAs) have been underappreciated as critical regulatory elements of many cellular biological
processes relevant to cancer development and progression. These IncRNAs may be targets for potent new
therapies to combat PCa progression. We have recently published the discovery of a novel lncRNA that acts as
an oncogene in PCa. This unannotated lncRNA is dramatically upregulated by androgen in a dose-dependent
manner and the hormone-induced increase is completely blocked by the anti-androgen enzalutamide. We have
named this lncRNA “HULLK” for Hormone-Upregulated lncRNA within LCK. HULLK transcripts are expressed in
patient tissue and there is a significant positive correlation between HULLK expression and high-grade PCa in
three independent cohorts: The Cancer Genome Atlas, the University of Virginia, and the University of Texas
Southwestern. Important for potential therapeutics, shRNAs specifically targeting HULLK significantly decreased
PCa cell growth, including CRPC cells expressing the ligand independent ARv7. These data lead to the
hypothesis that HULLK is a novel lncRNA that functions as a targetable oncogene in PCa. In this proposal we
will test HULLK as a driver of PCa in patient-derived xenograft in vivo models, provide proof-of-concept
therapeutic targeting of HULLK, and identify HULLK binding partners, which is the critical first step for
determining the molecular mechanism of HULLK. This proposal integrates innovative conceptual, technical, and
translational elements to uncover the molecular mechanisms through which HULLK drives PCa and to evaluate
HULLK as a potential therapeutic target in this devastating disease.
摘要
对于前列腺癌和去势抵抗性前列腺癌,仍然迫切需要更有效的疗法。
癌虽然局限性前列腺癌(PCa)具有良好的预后,但去势抵抗性前列腺癌(PCa)
CRPC仍然无法治愈。目前治疗的失败表明需要新的方法,
暴露了对驱动PCa至CRPC的潜在机制的不完整理解。长非编码
RNA(lncRNA)作为许多细胞生物学过程的关键调控元件一直被低估。
与癌症发展和进展相关的过程。这些IncRNA可能是有效的新靶点。
治疗以对抗PCa进展。我们最近发表了一种新的lncRNA的发现,
PCa中的癌基因。这种未注释的lncRNA被雄激素以剂量依赖性方式显著上调。
抗雄激素Enzalutamide可完全阻断雄激素诱导的增加。我们有
将这种lncRNA命名为“HULLK”,表示LCK内的激素上调的lncRNA。HULLK转录本在
患者组织中HULLK表达与高级别PCa之间存在显著正相关,
三个独立的队列:癌症基因组图谱,弗吉尼亚大学和德克萨斯大学
西南部对于潜在的治疗重要的是,特异性靶向HULLK的shRNA显著减少了
PCa细胞生长,包括表达配体非依赖性ARv 7的CRPC细胞。这些数据导致
假设HULLK是一种新的lncRNA,在PCa中作为靶向癌基因发挥作用。在本提案中,我们
将在患者来源的异种移植物体内模型中测试HULLK作为PCa的驱动因素,提供概念验证
HULLK的治疗靶向,并确定HULLK结合伴侣,这是关键的第一步,
确定HULLK的分子机制。该提案将创新的概念、技术和
翻译元件,以揭示HULLK驱动PCa的分子机制,并评估
HULLK作为这种毁灭性疾病的潜在治疗靶点。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Daniel G Gioeli其他文献
Daniel G Gioeli的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Daniel G Gioeli', 18)}}的其他基金
Checkpoint Signaling and Androgen Receptor Function in Prostate Cancer
前列腺癌中的检查点信号传导和雄激素受体功能
- 批准号:
9262061 - 财政年份:2014
- 资助金额:
$ 41.07万 - 项目类别:
Checkpoint Signaling and Androgen Receptor Function in Prostate Cancer
前列腺癌中的检查点信号传导和雄激素受体功能
- 批准号:
8691047 - 财政年份:2014
- 资助金额:
$ 41.07万 - 项目类别:
Role of Androgen Receptor Phosphorylation in Prostate Cancer
雄激素受体磷酸化在前列腺癌中的作用
- 批准号:
7663252 - 财政年份:2008
- 资助金额:
$ 41.07万 - 项目类别:
Role of Androgen Receptor Phosphorylation in Prostate Cancer
雄激素受体磷酸化在前列腺癌中的作用
- 批准号:
7523740 - 财政年份:2008
- 资助金额:
$ 41.07万 - 项目类别:
Role of Androgen Receptor Phosphorylation in Prostate Cancer
雄激素受体磷酸化在前列腺癌中的作用
- 批准号:
7841736 - 财政年份:2008
- 资助金额:
$ 41.07万 - 项目类别:
Role of Androgen Receptor Phosphorylation in Prostate Cancer
雄激素受体磷酸化在前列腺癌中的作用
- 批准号:
8278464 - 财政年份:2008
- 资助金额:
$ 41.07万 - 项目类别:
Role of Androgen Receptor Phosphorylation in Prostate Cancer
雄激素受体磷酸化在前列腺癌中的作用
- 批准号:
8115780 - 财政年份:2008
- 资助金额:
$ 41.07万 - 项目类别:
相似海外基金
Abnormalities in androgens and ovarian markers in reproductive-age racially and ethnically diverse women in a prospective longitudinal cohort
前瞻性纵向队列中不同种族和民族的育龄女性雄激素和卵巢标志物的异常
- 批准号:
10930196 - 财政年份:2023
- 资助金额:
$ 41.07万 - 项目类别:
Nonalcoholic Fatty Liver Disease (NAFLD) in Polycystic Ovary Syndrome: The Role of Androgens on Liver Injury and NAFLD Progression
多囊卵巢综合征中的非酒精性脂肪肝 (NAFLD):雄激素在肝损伤和 NAFLD 进展中的作用
- 批准号:
10735807 - 财政年份:2023
- 资助金额:
$ 41.07万 - 项目类别:
Sexual Differentiation of the Brain and Behaviour: Central and Peripheral Targets of Androgens
大脑和行为的性别分化:雄激素的中枢和外周目标
- 批准号:
RGPIN-2019-04999 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别:
Discovery Grants Program - Individual
Elucidation of the mechanisms by which cells recognize and respond to different levels of androgens
阐明细胞识别和响应不同水平雄激素的机制
- 批准号:
10418461 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别:
Influence of Androgens on Tissue-Specific Lipid Metabolites and Liver Injury in Young Women with NAFLD
雄激素对患有 NAFLD 的年轻女性组织特异性脂质代谢和肝损伤的影响
- 批准号:
10570208 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别:
Influence of Androgens on Tissue-Specific Lipid Metabolites and Liver Injury in Young Women with NAFLD
雄激素对患有 NAFLD 的年轻女性组织特异性脂质代谢和肝损伤的影响
- 批准号:
10355174 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别:
Paxillin and Androgens in the Regulation of Ovarian Follicle Development
桩蛋白和雄激素在卵巢卵泡发育调节中的作用
- 批准号:
10688086 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别:
Defining the impact of androgens on uterine immune cell function during endometrial tissue repair
确定子宫内膜组织修复过程中雄激素对子宫免疫细胞功能的影响
- 批准号:
2744296 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别:
Studentship
Use of novel 11-oxygenated androgens to improve diagnostic accuracy and therapeutics in polycystic ovary syndrome
使用新型 11-含氧雄激素提高多囊卵巢综合征的诊断准确性和治疗效果
- 批准号:
10431620 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别:
Paxillin and Androgens in the Regulation of Ovarian Follicle Development
桩蛋白和雄激素在卵巢卵泡发育调节中的作用
- 批准号:
10525097 - 财政年份:2022
- 资助金额:
$ 41.07万 - 项目类别: