Kaposi's Sarcoma-Associated Herpesvirus (KSHV) vIL-6 Promotes Cell Proliferation and Migration by Upregulating DNMT1 via STAT3 Activation

Wu, Jing; Xu, Yuqiao; Mo, Dongping; Huang, Peijun; Sun, Ruihong; Huang, Lei; Pan, Shiyang; Xu, Jian

doi:10.1371/journal.pone.0093478

Cited by 49 publications

(46 citation statements)

References 35 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 4A shows that approximately 1% of the total dCTP was methylated in the absence of aza-dC, which was consistent with previous findings [31,32] whereas the amount of methylated dCTP was reduced by approximately half within 1 day in the presence of aza-dC.…”

Section: Resultssupporting

confidence: 91%

Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine

2017

View full text Add to dashboard Cite

We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypomethylated, respectively and that 5-aza-2′-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 h in RPMI8402 cells. That is, such hypermethylation of CpG islands in the BMAL1 promoter restricted PER2 expression which was recovered by aza-dC within 1 day in these cells. These results suggest that the circadian clock system can be recovered through BMAL1 expression induced by aza-dC within a day. The RPIB9 promoter of RPMI8402 cells, which is a methylation hotspot in lymphoblastic leukemia, was also hypermethylated and aza-dC gradually recovered RPIB9 expression in 3 days. In addition, methylation-specific PCR revealed a different degree of aza-dC-induced methylation release between BMAL1 and RPIB9. These results suggest that the aza-dC-induced recovery of gene expression from DNA methylation is dependent on a gene, for example the rapid response to demethylation by the circadian system, and thus, is of importance to clinical strategies for treating cancer.

show abstract

Section: Resultssupporting

confidence: 91%

Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine

2017

View full text Add to dashboard Cite

show abstract

“…While this paper was under review, a paper showing similar effects of vIL-6 on migration was published (55).…”

mentioning

confidence: 99%

Modulation of Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Function by Hypoxia-Upregulated Protein 1

Giffin

Yan

Major

et al. 2014

J Virol

View full text Add to dashboard Cite

Kaposi's sarcoma-associated herpesvirus (KSHV, also called human herpesvirus 8) is linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV expresses several proteins that modulate host cell signaling pathways. One of these proteins is viral interleukin-6 (vIL-6), which is a homolog of human IL-6 (hIL-6). vIL-6 is able to prevent apoptosis and promote proinflammatory signaling, angiogenesis, and cell proliferation. Although it can be secreted, vIL-6 is mainly an intracellular protein that is retained in the endoplasmic reticulum (ER). We performed affinity purification and mass spectrometry to identify novel vIL-6 binding partners and found that a cellular ER chaperone, hypoxia-upregulated protein 1 (HYOU1), interacts with vIL-6. Immunohistochemical staining reveals that both PEL and KS tumor tissues express significant amounts of HYOU1. We also show that HYOU1 increases endogenous vIL-6 protein levels and that HYOU1 facilitates vIL-6-induced JAK/STAT signaling, migration, and survival in endothelial cells. Furthermore, our data suggest that HYOU1 also modulates vIL-6's ability to induce CCL2, a chemokine involved in cell migration. Finally, we investigated the impact of HYOU1 on cellular hIL-6 signaling. Collectively, our data indicate that HYOU1 is important for vIL-6 function and may play a role in the pathogenesis of KSHV-associated cancers. IMPORTANCEKSHV vIL-6 is detectable in all KSHV-associated malignancies and promotes tumorigenesis and inflammation. We identified a cellular protein, called hypoxia-upregulated protein 1 (HYOU1), that interacts with KSHV vIL-6 and is present in KSHV-infected tumors. Our data suggest that HYOU1 facilitates the vIL-6-induced signaling, migration, and survival of endothelial cells.

show abstract

“…65 Also, KSHV-encoded vIL-6 was shown to exploit the STAT3 pathway for genomic methylation by recruiting DNMT1 in endothelial cells. 90 …”

Section: Nm23-h1 Interaction With Epigenetic Modifiersmentioning

confidence: 99%

Oncogenic Epstein–Barr virus recruits Nm23-H1 to regulate chromatin modifiers

Pandey

Robertson

2018

Laboratory Investigation

View full text Add to dashboard Cite

In cancer progression, metastasis is a major cause of poor survival of patients and can be targeted for therapeutic interventions. The first discovered metastatic-suppressor Nm23-H1 possesses nucleoside diphosphate kinase, histidine kinase, and DNase activity as a broad-spectrum enzyme. Recent advances in cancer metastasis have opened new ways for the development of therapeutic molecular approaches. In this review, we provide a summary of the current understanding of Nm23/NDPKs in the context of viral oncogenesis. We also focused on Nm23-H1-mediated cellular events with an emphasis on chromatin modifications. How Nm23-H1 modulates the activities of chromatin modifiers through interaction with Epstein–Barr virus-encoded oncogenic antigens and related crosstalks are discussed in the context of other oncogenic viruses. We also described the current understanding of the cellular and viral interactions of Nm23-H1 and their reference to transcription regulation and metastasis. Further, we summarized the recent therapeutic approaches targeting Nm23 and its potential links to pathways that can be exploited by oncogenic viruses.

show abstract

Kaposi's Sarcoma-Associated Herpesvirus (KSHV) vIL-6 Promotes Cell Proliferation and Migration by Upregulating DNMT1 via STAT3 Activation

Cited by 49 publications

References 35 publications

Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine

Epigenetic regulation of the circadian clock: role of 5-aza-2′-deoxycytidine

Modulation of Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Function by Hypoxia-Upregulated Protein 1

Oncogenic Epstein–Barr virus recruits Nm23-H1 to regulate chromatin modifiers

Contact Info

Product

Resources

About