Global CpG DNA Methylation Footprint in Kaposi’s Sarcoma

Journo, Guy; Ahuja, Anuj; Dias‐Polak, David; Eran, Yonatan; Bergman, Reuven; Shamay, Meir

doi:10.3389/fcimb.2021.666143

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…The coding genes containing CpG islands are up to 60% in the usual state and are mostly nonmethylated, while CpG island hypermethylation in the promoter region of oncogenes has become a key marker in the carcinogenesis of some tumors and a common mechanism for transcriptional deletion of oncogenes [ 12 , 13 ]. Studies have shown that the methylation of CpG islands in the promoter region of oncogenes is progressively altered during the carcinogenesis of esophageal squamous carcinoma, and the inactivation of methylation-related genes will have a greater impact on various cell signaling pathways such as DNA damage repair system, apoptosis, and cell adhesion, thus participating in the development of esophageal carcinoma [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Diagnostic and Prognostic Value of DACH1 Methylation in the Sensitivity of Esophageal Cancer to Radiotherapy

Huang

Zhu

Wang

et al. 2022

Contrast Media & Molecular Imaging

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To detect the methylation status of the cell fate determinant (DACH1) gene in esophageal cancer tissues and to explore the predictive value of methylation of DACH1 on the sensitivity to radiotherapy for esophageal cancer. Cancer tissues, corresponding paracancerous tissues, and 30 specimens of normal esophageal mucosal tissues from 70 patients admitted to the hospital after radical esophageal cancer radiotherapy from January 2016 to April 2017 were collected. The methylation status of DACH1 was detected by a methylation-specific polymerase chain reaction (MSP). The 70 esophageal cancer patients were divided into radiotherapy-sensitive and radiotherapy-insensitive groups according to the efficacy of radiotherapy, and the methylation status of DACH1 was compared between the two groups. The χ2 test was used to analyze the relationship between the methylation status of DACH1 and the clinicopathological characteristics of esophageal cancer patients. The Kaplan–Meier survival curve was used to analyze the relationship between the methylation status of DACH1 and radiotherapy sensitivity and survival of esophageal cancer patients, and the Cox proportional risk model was used to analyze the independent influencing factors affecting the radiotherapy sensitivity of esophageal cancer patients. The methylation rate of DACH1 in esophageal cancer tissues was higher than that in paracancerous tissues and normal tissues, and the differences were statistically significant ( P < 0.05 ). 70 patients with esophageal cancer completed radiotherapy, including 46 patients with radiotherapy sensitivity and 24 patients with radiotherapy insensitivity. The DACH1 methylation rate of esophageal cancer patients in the radiotherapy-sensitive group was lower than that in the radiotherapy-insensitive group, and the difference was statistically significant ( P < 0.05 ). The DACH1 methylation rate of esophageal cancer patients with TNM stage (III-IV), tumor differentiation degree (hypofractionation), and lymph node metastasis was higher, and the difference was statistically significant ( P < 0.05 ). The Kaplan–Meier curve showed that the median survival time of patients with DACH1 methylation before radiotherapy was 23 months, which was shorter than that of patients with DACH1 unmethylation before radiotherapy (36 months), and the difference between the survival curves of the two groups was statistically significant (χ2 = 7.425, P < 0.05 ); the median survival time of patients in the radiotherapy-sensitive group was 39 months, which was longer than that of patients in the radiotherapy-insensitive group (25 months), and the difference between the two groups was statistically significant ( P < 0.05 ). The median survival time of patients in the radiotherapy-sensitive group was 39 months, which was longer than that of patients in the radiotherapy-insensitive group (25 months), and the difference in survival curves between the two groups was statistically significant (χ2 = 7.011, P < 0.05 ). The results of the multifactorial Cox regression model showed that TNM stage (stage III-IV) (HR = 1.961, 95% CI: 1.125–2.768), tumor hypofractionation (HR = 1.453, 95% CI: 1.034–2.857), presence of lymph node metastasis (HR = 1.499, 95% CI: 1.025–2.851), and DACH1 methylation (HR = 1.718, 95% CI: 1.067–2.596) may increase the risk of insensitivity to radiotherapy in patients with esophageal cancer ( P < 0.05 ). The rate of DACH1 methylation in esophageal cancer tissues was increased, and the methylation status of DACH1 was related to radiotherapy sensitivity and survival of esophageal cancer patients, which is expected to be a new target for diagnosis and treatment of esophageal cancer patients.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Diagnostic and Prognostic Value of DACH1 Methylation in the Sensitivity of Esophageal Cancer to Radiotherapy

Huang

Zhu

Wang

et al. 2022

Contrast Media & Molecular Imaging

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“…In a recent study by Journo et al (2021), the cellular CpG global methylation pattern was observed in KS infected biopsy samples [80]. Methylation EPIC BeadChip was performed to compare the global methylation pattern in normal skin cells and KS biopsy samples, which led to the conclusion that extensive global methylation alterations occur in KS.…”

Section: Dna Methylation In Kshv Infectionmentioning

confidence: 99%

“…These alterations can be attributed to the dramatic hypermethylation and hypomethylation of promoters and enhancers of genes that play a role in the regulation of abnormal skin morphology. An inference was made on this basis that hypermethylation occurs early in KS, followed by hypomethylation at a later stage [80].…”

Section: Dna Methylation In Kshv Infectionmentioning

confidence: 99%

Insight into the Epigenetics of Kaposi’s Sarcoma-Associated Herpesvirus

Srivastava,

Singh

2023

IJMS

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Epigenetic reprogramming represents a series of essential events during many cellular processes including oncogenesis. The genome of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic herpesvirus, is predetermined for a well-orchestrated epigenetic reprogramming once it enters into the host cell. The initial epigenetic reprogramming of the KSHV genome allows restricted expression of encoded genes and helps to hide from host immune recognition. Infection with KSHV is associated with Kaposi’s sarcoma, multicentric Castleman’s disease, KSHV inflammatory cytokine syndrome, and primary effusion lymphoma. The major epigenetic modifications associated with KSHV can be labeled under three broad categories: DNA methylation, histone modifications, and the role of noncoding RNAs. These epigenetic modifications significantly contribute toward the latent–lytic switch of the KSHV lifecycle. This review gives a brief account of the major epigenetic modifications affiliated with the KSHV genome in infected cells and their impact on pathogenesis.

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“…However, after 24 hours post infection (hpi), a transcriptionally repressive chromatin forms on the KSHV genome and is accompanied by the downregulation of viral lytic gene expression [4,6,7]. Several epigenetic mechanisms such as DNA methylation, chromatin remodeling, and the regulation of histone modifications on the viral chromatin have been implicated in the inhibition of lytic viral gene expression and subsequent establishment and maintenance of viral latency following primary infection [4,[8][9][10][11][12][13][14]. While lytic genes have many transcriptional repressors, Polycomb group proteins in particular have been shown to bind to KSHV lytic genes genomewide and are crucial for the inhibition of lytic genes [4,10,15,16].…”

Section: Introductionmentioning

confidence: 99%

PRC1-independent binding and activity of RYBP on the KSHV genome during de novo infection

Lee

Tóth

2022

PLoS Pathog

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Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic virus that causes lifelong infection in humans by establishing latency after primary infection. Latent infection is a prerequisite for both persistent infection and the development of KSHV-associated cancers. While viral lytic genes are transiently expressed after primary infection, their expression is significantly restricted and concomitant with the binding of host epigenetic repressors Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2) to lytic genes. PRC1 and PRC2 mediate the repressive histone marks H2AK119ub and H3K27me3, respectively, and maintain heterochromatin structure on KSHV lytic genes to inhibit their expression. In contrast to PRC2, little is known about the recruitment and role of PRC1 factors on the KSHV genome following de novo infection. Thus, the goal of this study was to examine the function of PRC1 factors in the establishment of KSHV latency. To address this question, we performed an shRNA screen targeting 7 different components of the canonical and non-canonical PRC1 complexes during primary KSHV infection. We found that RYBP, a main subunit of the non-canonical PRC1 complexes, is a potent repressor of KSHV lytic genes that can bind to the viral genome and inhibit lytic genes as early as 4 hours post infection. Surprisingly, our ChIP analyses showed that RYBP binds to lytic viral gene promoters in a PRC1-independent manner, does not affect PRC1 activity on the KSHV genome, and can reduce the level of histone marks associated with transcription elongation. Our data also suggest that RYBP can repress the viral lytic cycle after primary infection by inhibiting the transcription elongation of the lytic cycle inducer KSHV gene RTA. Based on our results we propose that RYBP uses a PRC1-independent mechanism to block KSHV RTA expression thereby promoting the establishment of KSHV latency following de novo infection.

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Global CpG DNA Methylation Footprint in Kaposi’s Sarcoma

Cited by 7 publications

References 35 publications

[Retracted] Diagnostic and Prognostic Value of DACH1 Methylation in the Sensitivity of Esophageal Cancer to Radiotherapy

[Retracted] Diagnostic and Prognostic Value of DACH1 Methylation in the Sensitivity of Esophageal Cancer to Radiotherapy

Insight into the Epigenetics of Kaposi’s Sarcoma-Associated Herpesvirus

PRC1-independent binding and activity of RYBP on the KSHV genome during de novo infection

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