Shugoshin 1 is dislocated by KSHV-encoded LANA inducing aneuploidy

Lang, Fengchao; Sun, Zhiguo; Pei, Yue‐Hu; Singh, Rajnish Kumar; Jha, Hem Chandra

doi:10.1371/journal.ppat.1007253

Cited by 13 publications

(10 citation statements)

References 70 publications

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“…Mu et al found that SGOL1 expression levels are higher in prostate cancer tissues, and SGLO1 knockdown results in the inhibition of tumor cell proliferation, migration, and invasion [42]. In addition, SGOL1 has been found in other cancers (e.g., breast cancer and glioblastoma) [43–45]. However, few studies have described the methylation state of SGOL1, and research on SGOL1 in CCA has been rarely reported.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Zhang

Meng

et al. 2019

Cancer Cell Int

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Background: The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylationregulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods:The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein-protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results:We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions:Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Zhang

Meng

et al. 2019

Cancer Cell Int

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“…LANA prevents Bub1-mediated phosphorylation of H2A at position T120 to influence Sgo1 localization, resulting in chromosomal instability [129] PEL cell lines (BC-3, JSC-1); in vitro infection (BJAB, HT1080); ectopic expression (BJAB, HEK293, HT1080)…”

Section: Viral Manipulation Of the Host Epigenomementioning

confidence: 99%

“…Lastly, a recent publication found that LANA interacts with Bub1, a component of the spindle checkpoint complex, to inhibit phosphorylation of histone 2A at residue T120 (H2AT120) [129]. LANA-dependent inhibition of H2AT120 phosphorylation resulted in dislocation of Sgo1, a protein which protects centromere integrity, and induction of aneuploidy.…”

Section: Rta (Lytic)mentioning

confidence: 99%

Epigenetic control in Kaposi sarcoma-associated herpesvirus infection and associated disease

Fröhlich

Grundhoff

2020

Semin Immunopathol

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Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several malignancies of endothelial and B-cell origin. The fact that latently infected tumor cells in these malignancies do not express classical viral oncogenes suggests that pathogenesis of KSHV-associated disease results from multistep processes that, in addition to constitutive viral gene expression, may require accumulation of cellular alterations. Heritable changes of the epigenome have emerged as an important co-factor that contributes to the pathogenesis of many non-viral cancers. Since KSHV encodes a number of factors that directly or indirectly manipulate host cell chromatin, it is an intriguing possibility that epigenetic reprogramming also contributes to the pathogenesis of KSHV-associated tumors. The fact that heritable histone modifications have also been shown to regulate viral gene expression programs in KSHV-infected tumor cells underlines the importance of epigenetic control during latency and tumorigenesis. We here review what is presently known about the role of epigenetic regulation of viral and host chromatin in KSHV infection and discuss how viral manipulation of these processes may contribute to the development of KSHV-associated disease.

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“…LANA, in addition to tethering of the KSHV genome regulates several cellular functions required for oncogenic transformation of infected cells. The major pathways modulated by KSHV-encoded LANA include cell cycle[19], apoptosis[20], Epithelial-Mesenchymal transition (EMT)[21, 22] and chromosome instability (CIN)[23]. Nevertheless, other KSHV-encoded latent genes also plays a major role in oncogenic transformation of infected cells.…”

Section: Introductionmentioning

confidence: 99%

KSHV-encoded vCyclin can modulate HIF1α levels to promote DNA replication in hypoxia

Singh

Pei

Lamplugh

et al. 2020

Preprint

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The cellular adaptive response to hypoxia, mediated by high HIF1α levels includes metabolic reprogramming, restricted DNA replication and cell division. In contrast to healthy cells, the genome of cancer cells, and Kaposi’s sarcoma associated herpesvirus (KSHV) infected cells maintains replication in hypoxia. We show that KSHV infection, despite promoting expression of HIF1α in normoxia, can also restricts transcriptional activity, and promoted its degradation in hypoxia. KSHV-encoded vCyclin, expressed in hypoxia, mediated HIF1a cytosolic translocation, and its degradation through a non-canonical lysosomal pathway. Attenuation of HIF1α levels by vCyclin allowed cells to bypass the block to DNA replication and cell proliferation in the hypoxia. These results demonstrated that KSHV utilizes a unique strategy to balance HIF1α levels to overcome replication arrest and induction of the oncogenic phenotype, which are dependent on the levels of oxygen in the microenvironment.

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Shugoshin 1 is dislocated by KSHV-encoded LANA inducing aneuploidy

Cited by 13 publications

References 70 publications

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Epigenetic control in Kaposi sarcoma-associated herpesvirus infection and associated disease

KSHV-encoded vCyclin can modulate HIF1α levels to promote DNA replication in hypoxia

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