ArticlePLoS pathogens2015
A KSHV microRNA Directly Targets G Protein-Coupled Receptor Kinase 2 to Promote the Migration and Invasion of Endothelial Cells by Inducing CXCR2 and Activating AKT Signaling.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 82 citations in OpenAlex.
- The HCMV-encoded miR-UL36-3p promotes angiogenesis of endothelial cells by downregulating FOXO3.Animal models and experimental medicine · 2026Article
- miR-181a post-transcriptionally targets GRK2 to limit maladaptive signaling in cardiomyocytes.Frontiers in cardiovascular medicine · 2026Article
- Heterogeneous Activation of Signaling Pathways and Therapeutic Vulnerabilities in KSHV-Associated Primary Effusion Lymphoma Cell Lines.Journal of medical virology · 2025Article
- Exome Sequencing Reveals a Sparse Genomic Landscape in Kaposi Sarcoma.Molecular cancer research : MCR · 2025Article
- Hepatitis B virus confers innate immunity evasion through hepatitis B virus-miR-3 down-regulation of cGAS-Sting-IFN signaling.World journal of hepatology · 2025Article
- G-protein coupled receptor kinase-2 regulates the migration of chronic lymphocytic leukaemia cells to sphingosine-1 phosphate in vitro and their trafficking in vivo.Scientific reports · 2025Article
- Lactylation of RNA mProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB.NPJ Regenerative medicine · 2024Article
- From enhancers to genome conformation: complex transcriptional control underlies expression of a single herpesviral gene.bioRxiv : the preprint server for biology · 2024Article
- KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation.PLoS pathogens · 2024Article
- Viral miRNA regulation of host gene expression.Seminars in cell & developmental biology · 2023Review
- Immune evasion strategy involving propionylation by the KSHV interferon regulatory factor 1 (vIRF1).PLoS pathogens · 2023Article
- A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA.Cell death and differentiation · 2022Article
- Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology.Microorganisms · 2022Review
- Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms.Diagnostics (Basel, Switzerland) · 2022Review
- Human herpesvirus-encoded MicroRNA in host-pathogen interaction.Advances in biological regulation · 2021Review
- The GRKs Reactome: Role in Cell Biology and Pathology.International journal of molecular sciences · 2021Review
- 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.PLoS pathogens · 2021Article
- Potential Regulatory Roles of GRK2 in Endothelial Cell Activity and Pathological Angiogenesis.Frontiers in immunology · 2021Review
- A Non-Coding RNA Network Involved in KSHV Tumorigenesis.Frontiers in oncology · 2021Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Kaposi's sarcoma (KS) is a highly disseminated angiogenic tumor of endothelial cells linked to infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV encodes more than two dozens of miRNAs but their roles in KSHV-induced tumor dissemination and metastasis remain unknown. Here, we found that ectopic expression of miR-K12-3 (miR-K3) promoted endothelial cell migration and invasion. Bioinformatics and luciferase reporter analyses showed that miR-K3 directly targeted G protein-coupled receptor (GPCR) kinase 2 (GRK2, official gene symbol ADRBK1). Importantly, overexpression of GRK2 reversed miR-K3 induction of cell migration and invasion. Furthermore, the chemokine receptor CXCR2, which was negatively regulated by GRK2, was upregulated in miR-K3-transduced endothelial cells. Knock down of CXCR2 abolished miR-K3-induced cell migration and invasion. Moreover, miR-K3 downregulation of GRK2 relieved its direct inhibitory effect on AKT. Both CXCR2 induction and the release of AKT from GRK2 were required for miR-K3 maximum activation of AKT and induction of cell migration and invasion. Finally, deletion of miR-K3 from the KSHV genome abrogated its effect on the GRK2/CXCR2/AKT pathway and KSHV-induced migration and invasion. Our data provide the first-line evidence that, by repressing GRK2, miR-K3 facilitates cell migration and invasion via activation of CXCR2/AKT signaling, which likely contribute to the dissemination of KSHV-induced tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.