权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

KSHV microRNAs in tumor invasion and angiogenesis

KSHV microRNA 在肿瘤侵袭和血管生成中的作用

基本信息

批准号：
10264784
负责人：
Shou-Jiang Gao
金额：
$ 18.97万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
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：
2017-03-03 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10264784
关键词：
Acquired Immunodeficiency Syndrome Binding Cells China Clinical Trials Coupled Development Etiology Funding G protein coupled receptor kinase Genome Glutamic Acid Goals Herpesviridae Infections Highly Active Antiretroviral Therapy Human Human Herpesvirus 8 Individual Kaposi Sarcoma Laboratories Malignant - descriptor Malignant Neoplasms Mediating Mesenchymal Stem Cells MicroRNAs Modeling Molecular Morbidity - disease rate Multicentric Angiofollicular Lymphoid Hyperplasia Mutagenesis Mutate Organ Pathologic Pathway interactions Patients Phosphotransferases Prevention Proteins Proto-Oncogene Proteins c-akt Role SH3 Domains STAT3 gene Signal Transduction Site Societies Therapeutic Time Tumor Angiogenesis Tumor Cell Invasion Viral Visceral angiogenesis cellular targeting inhibitor/antagonist innovation insight mortality novel novel therapeutic intervention overexpression primary effusion lymphoma programs receptor therapeutic target tumor tumorigenesis

项目摘要

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several cancers. Despite highly active anti-retroviral therapy, Kaposi’s sarcoma (KS) remains as a dominant cancer in AIDS patients. The hallmark pathological features of KS are excessive deregulation of angiogenesis and extreme invasiveness manifested as multifocal tumors and involvement of visceral organs. Thus, understanding the molecular basis of KSHV-induced angiogenesis and cell invasion could serve as the basis for developing novel therapeutic approaches. Our US-China collaborative team funded by previous cycle of the US-China Program has made significant progresses toward this goal by 1) developing a novel model of KSHV infection of human primary mesenchymal stem cells (MSCs), in which KSHV induces angiogenesis, cell invasion, malignant transformation and tumorigenesis closely mimicking human KS tumors;; 2) demonstrating the essential roles of KSHV microRNAs (miRNAs) in KSHV-induced angiogenesis and cell invasion;; 3) identifying KSHV miR-K6-3p as a pro-angiogenic miRNA that induces angiogenesis by targeting SH3 domain-binding glutamic acid-rich protein (SH3BGR) to activate the STAT3 pathway;; and 4) demonstrating that KSHV miR-K3-5p promotes cell invasion by targeting G-protein coupled receptor kinase 2 (GRK2) to activate the AKT signaling. We propose to extend these exciting discoveries with the objective to further dissect the molecular mechanisms by which KSHV miRNAs promote tumorigenesis by inducing angiogenesis and cell invasion, and to explore the therapeutic application of these discoveries. The central hypothesis is that KSHV encodes specific miRNAs to activate angiogenic and invasive pathways contributing to KSHV-induced tumorigenesis, and as a result, targeting these pathways can effectively inhibit the development of KSHV-induced cancers. We will identify KSHV miRNAs that mediate KSHV-induced angiogenesis and define the mechanisms of action (Aim 1);; identify KSHV miRNAs that mediate KSHV-induced cell invasion and define the mechanisms of action (Aim 2);; delineate the roles of pro-angiogenic and pro-invasive miRNAs in the development of tumors, and in tumor angiogenesis and invasion (Aim 3);; and explore the therapeutic application of targeting angiogenic and invasive pathways activated by KSHV miRNAs in KSHV-induced tumorigenesis (Aim 4). This application will further reinforce the collaborative efforts of the two US and China teams with highly complementary expertise to accelerate the advancements of the proposed project that are otherwise difficult to achieve by the individual laboratories. The results from this project will be highly significant and innovative because they will, for the first time, define the functions and mechanisms of action of KSHV miRNAs in tumor angiogenesis and invasion in a genuine KS model, and identify novel targets for developing innovative therapeutic approaches. The study will also establish a novel paradigm of oncogenesis mediated by viral subversion of the miRNA pathway, thus providing insights into the oncogenesis of other cancers.

卡波西肉瘤相关疱疹病毒（KSHV）是几种癌症的病因。尽管高

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Correction: A viral microRNA downregulates metastasis suppressor CD82 and induces cell invasion and angiogenesis by activating the c-Met signaling.

更正：病毒 microRNA 下调转移抑制因子 CD82，并通过激活 c-Met 信号传导诱导细胞侵袭和血管生成。

DOI：
10.1038/s41388-021-01823-4
发表时间：
2021
期刊：
Oncogene
影响因子：
8
作者：
Li,W;Hu,M;Wang,C;Lu,H;Chen,F;Xu,J;Shang,Y;Wang,F;Qin,J;Yan,Q;Krueger,BJ;Renne,R;Gao,S-J;Lu,C
通讯作者：
Lu,C

CircRNA ARFGEF1 functions as a ceRNA to promote oncogenic KSHV-encoded viral interferon regulatory factor induction of cell invasion and angiogenesis by upregulating glutaredoxin 3.

CircRNA ARFGEF1 作为 ceRNA 发挥作用，通过上调谷氧还蛋白 3 促进致癌 KSHV 编码的病毒干扰素调节因子诱导细胞侵袭和血管生成