Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies
Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies
批准号:
10812041
负责人:
ROLF F RENNE
金额:
$4.3万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-07-01 至 2027-01-31
关键词:
Acquired Immunodeficiency SyndromeB-Cell LymphomasBinding ProteinsBiological AssayBiologyCodeDataData SetEndothelial CellsGenesGoalsHerpesviridaeHerpesviridae InfectionsHumanHuman Herpesvirus 4Human Herpesvirus 8HybridsKaposi SarcomaLinkMALAT1 geneMalignant NeoplasmsMessenger RNAMicroRNAsModelingMultiomic DataPathogenicityPhenotypeProliferatingProteinsProtocols documentationRNARNA SplicingReportingRoleSamplingSignal PathwayStructureTechniquesTranscriptUntranslated RNAViralVirusVirus Diseasesangiogenesiscircular RNAcomparativecrosslinkgammaherpesvirusgene regulatory networkglucose metabolisminnovationmigrationprimary effusion lymphomaprogramstranscriptome sequencingtumor
中文摘要
项目总结
卡波西肉瘤相关疱疹病毒(KSHV)是一种人类伽玛疱疹病毒,是艾滋病的病原体
恶性疾病,如KS和原发性渗出性淋巴瘤(PEL)。近年来,致病性变得越来越明显
包括EBV、KSHV和MHV68在内的疱疹病毒表达大量的长非编码RNA(LncRNAs),其中许多
它们与蛋白质编码转录本处于反义定向。这些RNAs的功能和结构如下
很大程度上是未知的。此外,这些病毒还表达microRNAs(MiRNAs)。在描述KSHV的同时
使用一种改进的杂交(QClash)交联法和测序方法,我们鉴定了miRNA靶体
数百个宿主细胞中的lncRNAs可能是miRNA的靶标。这些数据强烈表明,KSHV和KSHV
编码的蛋白质和miRNAs参与了宿主lncRNAs的失调。重要的是,34个lncRNA是
报道了KSHV感染后的扰动,包括MALAT1,HotTip,ANRIL,Meg3,UCA1和GAS-5
与人类癌症有关。我们还将mrna和lncRNA靶标与癌症标志联系起来。
表型,如增殖、迁移、血管生成和葡萄糖代谢,并开始识别
作为KS模型的人内皮细胞中受KSHV miRNAs干扰的信号通路。我们也
异常剪接被确定为另一种癌症标志表型。在这里,我们建议扩展我们的研究范围
通过整合QClash、RNAseq和miRNAseq数据中的多个组学数据集来综合分析
KSHV感染的内皮细胞中miRNA调控的基因调控网络。此外,我们还建议验证
我们在大量人类肿瘤样本中的发现,并通过产生第一个KS肿瘤miRNA
由QClash提供的Target ome。这些研究将与项目2和项目3进行比较
此外,还将由核心B、C和D支持。此外,我们正在从功能上研究
反义LANA转录本(ALT),我们已经用高度的
创新的RNA下拉试验。此外,我们还将研究一类新发现的病毒环状RNA的作用。
它已经被这个程序发现了。总而言之,这个项目的目标是描绘病毒的作用
在艾滋病恶性肿瘤中受病毒感染干扰的lncRNA和宿主细胞lncRNAs。
英文摘要
PROJECT SUMMARY
Kaposi's sarcoma-associated herpesvirus (KSHV), a human gamma-herpesvirus, is the causative agent of AIDS
malignancies like KS and primary effusion lymphomas (PEL). In recent years it became clear that pathogenic
herpesviruses including EBV, KSHV, and MHV68 express numerous long non-coding RNAs (lncRNAs) many of
which are in antisense orientation to protein coding transcripts. The function and structure of these RNAs is
largely unknown. In addition, these viruses express microRNAs (miRNAs). While characterizing the KSHV
miRNA targetomes using a modified Crosslinking and Sequencing of Hybrids (qCLASH) protocol, we identified
several hundred host cellular lncRNAs as putative miRNA targets. These data strongly suggest that both KSHV
encoded proteins and miRNAs contribute to dysregulation of host lncRNAs. Importantly, 34 lncRNAs that are
perturbed following KSHV infection, including MALAT1, HOTTIP, ANRIL, Meg3, UCA1 and GAS-5 are reported
to be associated with human cancers. We also linked both mRNA and lncRNA targets to cancer hallmark
phenotypes such as proliferation, migration, angiogenesis, and glucose metabolism, and started to identify
signaling pathways that are perturbed by KSHV miRNAs in human endothelial cells as a model for KS. We also
identified aberrant splicing as an additional cancer hallmark phenotype. Here we propose to extend our studies
by integrating multi-omics data sets from qCLASH, RNAseq and miRNAseq data to comprehensively analyze
miRNA-regulated gene regulatory networks in KSHV infected endothelial cells. Moreover, we propose to validate
our findings in a significant number of human tumor samples and by generating the first KS tumor miRNA
targetome by qCLASH. These studies will be performed in a comparative fashion with Projects 2 and 3 and
furthermore will be supported by Cores B, C, and D. In addition, we are functionally studying the role of the
antisense LANA transcript (ALT) for which we have identified 81 putative binding proteins using a highly
innovative RNA-pulldown assay. Moreover, we will study the role of a newly identified class of viral circular RNAs
that has been discovered by this program. In summary, the goal of this project is to delineate the role of viral
lncRNAs and host cellular lncRNAs that are perturbed by viral infection in AIDS malignancies.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
"Project 1" KSHV short and long noncoding RNAs and alteration of host IncRNA expression
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批准号:10865781
-
项目类别:
-
资助金额:$4.3万
-
财政年份:2023
-
负责人:ROLF F RENNE
-
依托单位:
The Role of H3.3 histone variant in the pathogenesis of oral Kaposi's Sarcoma
-
批准号:10418661
-
项目类别:
-
资助金额:$35.53万
-
财政年份:2018
-
负责人:ROLF F RENNE
-
依托单位:
"Project 1" KSHV short and long noncoding RNAs and alteration of host IncRNA expression
-
批准号:10403015
-
项目类别:
-
资助金额:$29.3万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
"Project 1" KSHV short and long noncoding RNAs and alteration of host IncRNA expression
-
批准号:10646225
-
项目类别:
-
资助金额:$29.3万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
"Core A" Administrative Core
-
批准号:10403018
-
项目类别:
-
资助金额:$11.0万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies
-
批准号:10646224
-
项目类别:
-
资助金额:$150.57万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
"Core A" Administrative Core
-
批准号:10646248
-
项目类别:
-
资助金额:$11.03万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
"Core C" Recombinant Virus Core
-
批准号:10646256
-
项目类别:
-
资助金额:$13.26万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
"Core C" Recombinant Virus Core
-
批准号:10403020
-
项目类别:
-
资助金额:$12.48万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies
-
批准号:9266979
-
项目类别:
-
资助金额:$135.64万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies
-
批准号:10818838
-
项目类别:
-
资助金额:$4.68万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
Noncoding RNAs in gamma-Herpesvirus Biology and AIDS Malignancies
-
批准号:10403014
-
项目类别:
-
资助金额:$156.95万
-
财政年份:2017
-
负责人:ROLF F RENNE
-
依托单位:
Histone variant H3.3 and KSHV LANA in the pathogenesis of oral Kaposi's sarcoma
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批准号:8889664
-
项目类别:
-
资助金额:$18.6万
-
财政年份:2014
-
负责人:ROLF F RENNE
-
依托单位:
Histone variant H3.3 and KSHV LANA in the pathogenesis of oral Kaposi's sarcoma
-
批准号:8790233
-
项目类别:
-
资助金额:$22.36万
-
财政年份:2014
-
负责人:ROLF F RENNE
-
依托单位:
12th International Workshop on KSHV and Related Agents
-
批准号:7675539
-
项目类别:
-
资助金额:$1.8万
-
财政年份:2009
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负责人:ROLF F RENNE
-
依托单位:
Building a recombinant Herpesvirus core laboratory to systematically analyze the
-
批准号:7942972
-
项目类别:
-
资助金额:$50.0万
-
财政年份:2009
-
负责人:ROLF F RENNE
-
依托单位:
Building a recombinant Herpesvirus core laboratory to systematically analyze the
-
批准号:7854855
-
项目类别:
-
资助金额:$50.0万
-
财政年份:2009
-
负责人:ROLF F RENNE
-
依托单位:
Studying the role of KSHV-encoded microRNAs
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批准号:8197308
-
项目类别:
-
资助金额:$28.61万
-
财政年份:2007
-
负责人:ROLF F RENNE
-
依托单位:
Studying the role of KSHV-encoded microRNAs
-
批准号:7418877
-
项目类别:
-
资助金额:$41.3万
-
财政年份:2007
-
负责人:ROLF F RENNE
-
依托单位:
Studying the role of KSHV-encoded miRNAs
-
批准号:8620613
-
项目类别:
-
资助金额:$29.2万
-
财政年份:2007
-
负责人:ROLF F RENNE
-
依托单位:
海外基金