Kaposi's sarcoma‐associated herpesvirus (KSHV)‐encoded microRNAs promote matrix metalloproteinases (MMPs) expression and pro‐angiogenic cytokine secretion in endothelial cells

Guo, Yuanyuan; Wan, Li; Qin, Jie; Liu, Chun; Fan, Weifei

doi:10.1002/jmv.24773

Cited by 11 publications

(10 citation statements)

References 48 publications

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“…Numerous KSHV miRNAs induce inflammation by activating the NF-κB pathway [112,242]. Ectopic expression of the miRNA cluster in endothelial cells induces the expression of pro-inflammatory and proangiogenic cytokines MMP1, MMP13, and VEGFA [286]. VEGF is important for the recruitment of stem cells and macrophages at the site of infection, and therefore participates in the inflammatory microenvironment of KS tumors [287].…”

Section: Latent Viral Factors Involved In Inflammationmentioning

confidence: 99%

Molecular Biology of KSHV in Relation to HIV/AIDS-Associated Oncogenesis

He¹,

Cheng²,

Silva³

et al. 2018

Cancer Treatment and Research

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Discovered in 1994, KSHV is a human oncogenic gammaherpesvirus [1]. KSHV is causatively associated with several malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and KSHV inflammatory cytokine syndrome (KICS), most of which are commonly found in HIV-1infected individuals [1,2,3,4]. KS is a multifocal mesenchymal neoplasm characterized by neo-angiogenesis, inflammatory infiltration, and spindle-shaped tumor cells that express mixed cellular markers, including vascular and lymphatic endothelial, mesenchymal, and hematopoietic precursor cells [5]. Early stage of KS primarily affects mucocutaneous tissues but advanced stage of KS is often involved with visceral organs [5]. KS is one of the most common malignancies in AIDS patients. While the advent of antiretroviral therapy has substantially reduced the incidence of KS in Western countries, it has stabilized or even rebound in recent years in some populations, and continues to be the most common cancer in some African regions [6]. Hence, KS remains to be one of the most important malignancies in AIDS patients causing significant morbidity and mortality.PEL is a rare and aggressive non-Hodgkin's B cell lymphoma clinically characterized by lymphomatous effusions in body cavities usually without tumor masses [7]. PEL often occurs in advanced AIDS patients with a decreased CD4 T cell count at diagnosis. Approximately, half of PEL patients have KS or are at risk for developing KS. PEL is resistant to conventional chemotherapy with a short median survival of less than 6 months [7].MCD is a polyclonal B cell lymphoproliferative disorder characterized by inflammatory symptoms, including fever, cachexia, lymphadenopathy, splenomegaly, cytopenia, and hypoalbuminemia [8]. MCD in the setting of HIV is typically associated with KSHV infection and is usually fatal without treatment. Furthermore, there is no established standard of treatment for KSHV-associated MCD [8].

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Section: Latent Viral Factors Involved In Inflammationmentioning

confidence: 99%

Molecular Biology of KSHV in Relation to HIV/AIDS-Associated Oncogenesis

He¹,

Cheng²,

Silva³

et al. 2018

Cancer Treatment and Research

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“…Along with in-depth analyses of microRNAs (miRNAs or miRs), certain studies have suggested that upregulation of miRNAs can inhibit MMP13 expression (9,10). miRNAs are associated with regulating differentiation and maturation of immune cells, including T cells and B cells (11); osteogenic differentiation of stromal cells (12); expression of inflammatory cytokines and immune responses (13); host-virus interactions (14); and the sugar metabolism in the body (15).…”

Section: Introductionmentioning

confidence: 99%

miRNA‑155 expression and role in pathogenesis in spinal tuberculosis‑induced intervertebral disc destruction

Yang

Shi

et al. 2019

Exp Ther Med

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The current study aimed to investigate microRNA-155 (miR-155) expression in spinal tuberculosis-induced intervertebral disc destruction and its regulatory role in disease pathogenesis. A total of 26 patients with intervertebral disc destruction induced by spinal tuberculosis and 31 healthy individuals were included. Reverse transcription-quantitative polymerase chain reactions, western blot analysis and ELISA were performed to detect mRNA and protein expression levels. A bioinformatics analysis was applied to predict the upstream regulator of matrix metalloproteinase (MMP)13, which was confirmed by dual-luciferase reporter assay. Compared with the control group, mRNA and protein expression levels of MMP13 were significantly increased in the intervertebral disc of patients with spinal tuberculosis. However, miR-155 expression in the intervertebral disc of patients with spinal tuberculosis was significantly decreased compared with the control group. Dual-luciferase reporter assays suggested that miR-155 bound to the 3′-untranslated region of MMP13 to regulate gene expression. In primary annulus fibrosus cells, upregulated miR-155 expression significantly decreased MMP13 expression in the cells and culture supernatant, whereas it increased type II collagen expression. Upregulated MMP13 expression in the intervertebral disc in patients with spinal tuberculosis may be correlated with downregulated miR-155 expression. miR-155 may regulate expression levels of associated proteins in the intervertebral disc via modulating MMP13 expression, which contributes to the disease pathogenesis. The results of the current study may provide the theoretical basis for the diagnosis and treatment of disc damages caused by spinal tuberculosis.

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“…For instance, KSHV vIL-6 induced VEGFA expression, which promoted vascular permeability [64] while K1 promoted the expression and release of VEGFA [65]. Furthermore, KSHV miRNAs also increased the expression of VEGFA, as well as the secretion of VEGFA protein [66,67]. It is well known that activation of JNK signaling induces VEGFA production [33,68].…”

Section: Plos Pathogensmentioning

confidence: 99%

Sperm associated antigen 9 promotes oncogenic KSHV-encoded interferon regulatory factor-induced cellular transformation and angiogenesis by activating the JNK/VEGFA pathway

Wan¹,

Wang²,

Shi³

et al. 2020

PLoS Pathog

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Kaposi's sarcoma (KS), caused by Kaposi's sarcoma-associated herpesvirus (KSHV), is a highly angioproliferative disseminated tumor of endothelial cells commonly found in AIDS patients. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) mediates KSHV-induced cell motility (PLoS Pathog. 2019 Jan 30;15(1):e1007578). However, the role of vIRF1 in KSHV-induced cellular transformation and angiogenesis remains unknown. Here, we show that vIRF1 promotes angiogenesis by upregulating sperm associated antigen 9 (SPAG9) using two in vivo angiogenesis models including the chick chorioallantoic membrane assay (CAM) and the matrigel plug angiogenesis assay in mice. Mechanistically, vIRF1 interacts with transcription factor Lef1 to promote SPAG9 transcription. vIRF1-induced SPAG9 promotes the interaction of mitogen-activated protein kinase kinase 4 (MKK4) with JNK1/2 to increase their phosphorylation, resulting in enhanced VEGFA expression, angiogenesis, cell proliferation and migration. Finally, genetic deletion of ORF-K9 from KSHV genome abolishes KSHV-induced cellular transformation and impairs angiogenesis. Our results reveal that vIRF1 transcriptionally activates SPAG9 expression to promote angiogenesis and tumorigenesis via activating JNK/VEGFA signaling. These novel findings define the mechanism of KSHV induction of the SPAG9/JNK/ VEGFA pathway and establish the scientific basis for targeting this pathway for treating KSHV-associated cancers.

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Kaposi's sarcoma‐associated herpesvirus (KSHV)‐encoded microRNAs promote matrix metalloproteinases (MMPs) expression and pro‐angiogenic cytokine secretion in endothelial cells

Cited by 11 publications

References 48 publications

Molecular Biology of KSHV in Relation to HIV/AIDS-Associated Oncogenesis

Molecular Biology of KSHV in Relation to HIV/AIDS-Associated Oncogenesis

miRNA‑155 expression and role in pathogenesis in spinal tuberculosis‑induced intervertebral disc destruction

Sperm associated antigen 9 promotes oncogenic KSHV-encoded interferon regulatory factor-induced cellular transformation and angiogenesis by activating the JNK/VEGFA pathway

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