Epigenetic Regulation of Inflammatory Cytokines and Associated Genes in Human Malignancies

Yasmin, Rehana; Siraj, Sami; Hassan, Amjad; Khan, Abdul Rehman; Abbasi, Rashda; Ahmad, Nafees

doi:10.1155/2015/201703

Cited by 102 publications

(90 citation statements)

References 103 publications

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“…H2Bub1 was previously shown to promote ER target gene expression, 21,27 in conjunction with the histone chaperone SUPT6H. 21 In agreement, RNF20 silencing in luminal cancer cells decreased the expression of the ER targets PGR and CXCL12 (Figure 4c), which can drive breast cancer progression, proliferation and migration, 31,32 as well as of FOXA1, encoding the pioneer transcription factor regulating ER function. 33 The same genes were downregulated also in RNF20-silenced MCF7-RAS cells (Supplementary Figure S5A).…”

Section: Resultssupporting

confidence: 65%

RNF20 and histone H2B ubiquitylation exert opposing effects in Basal-Like versus luminal breast cancer

et al. 2017

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Breast cancer subtypes display distinct biological traits that influence their clinical behavior and response to therapy. Recent studies have highlighted the importance of chromatin structure regulators in tumorigenesis. The RNF20-RNF40 E3 ubiquitin ligase complex monoubiquitylates histone H2B to generate H2Bub1, while the deubiquitinase (DUB) USP44 can remove this modification. We found that RNF20 and RNF40 expression and global H2Bub1 are relatively low, and USP44 expression is relatively high, in basal-like breast tumors compared with luminal tumors. Consistent with a tumor-suppressive role, silencing of RNF20 in basal-like breast cancer cells increased their proliferation and migration, and their tumorigenicity and metastatic capacity, partly through upregulation of inflammatory cytokines. In contrast, in luminal breast cancer cells, RNF20 silencing reduced proliferation, migration and tumorigenic and metastatic capacity, and compromised estrogen receptor transcriptional activity, indicating a tumor-promoting role. Notably, the effects of USP44 silencing on proliferation and migration in both cancer subtypes were opposite to those of RNF20 silencing. Hence, RNF20 and H2Bub1 have contrasting roles in distinct breast cancer subtypes, through differential regulation of key transcriptional programs underpinning the distinctive traits of each subtype.

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Section: Resultssupporting

confidence: 65%

RNF20 and histone H2B ubiquitylation exert opposing effects in Basal-Like versus luminal breast cancer

et al. 2017

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“…The T-bet region, as one vital bivalent domain, can be activated by removal of the H3K27me3 suppressive effect and can thereby promote Th1 cell plasticity through elevated IL-12Rβ2 expression. In contrast, upregulated IL-23R expression is associated with Th17 cell plasticity with maintenance of the H3K27me3 effect by TGF-β1 [45,47]. However, the precise role of IL-23 on Th17 cell plasticity remains unclear and requires further research within the tumor microenvironment.…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 99%

Combined Effect of IL-12Rβ2 and IL-23R Expression on Prognosis of Patients with Laryngeal Cancer

Tao

Gross

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study aimed to pathologically elucidate the roles of interleukin-12 receptor (IL-12R) β2 and interleukin-23 receptor (IL-23R) expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment and to determine their combined effect on prognosis of laryngeal cancer (LC). Methods: The tumor-cell expression scores and TIL positivity ratiosof IL-12Rβ2 and IL-23R in matched LC and normal laryngeal tissue samples from 61 LC patients were measured via immunohistochemistry (IHC). We adopted a linear regression model to analyze the correlation between IL-12Rβ2 and IL-23R expression in tumor cells and TIL ratios. TheKaplan-Meier log-rank test and Cox regression hazard ratios were used to analyze survival. Results: LC tumor cells had a higher IL-12Rβ2 expression and TIL ratio than IL-23R expression and TIL ratio. The significant correlations between IL-12Rβ2 and IL-23R expression and TIL ratios were identified in LC tissues, particularly in well-differentiated LC. Furthermore, either high tumor cell IL-12Rβ2 or low IL-23R expression had better survival than its corresponding low or high expression, respectively. Similar results did for IL-12Rβ2 ratio and IL-23R ratio. Finally, patients with both high IL-12Rβ2 and low IL-23R had the best prognosis among any other combined groups with both gene expression (HR, 0.1; 95% CI, 0.0-0.8). Likewise, patients with positive ratios of high IL-12Rβ2 and low IL-23R TILs had the best survival (HR, 0.1; 95% CI, 0.0-0.4). Conclusion: IL-12Rβ2 and IL-23R create a homeostasis within the tumor cells and TILs, and this homeostasis affects prognosis. While the intrinsic mechanisms of epigenetic immunoediting for IL-12Rβ2 and IL-23R remain unknown, additional larger and functional studies are warranted for validation.

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“…Thus, altered expression of genes associated with immunity and inflammation might act as a predisposing factor for carcinogenesis. There are numerous lines of evidence to show the altered epigenetic modulation of inflammatory cytokines and genes related to immune function during cervical carcinogenesis [105] . Interestingly, these genes can even be targeted by HPV oncoproteins.…”

Section: The Immune System Epigenetics and Cervical Cancermentioning

confidence: 99%

Epigenomics, Pharmacoepigenomics, and Personalized Medicine in Cervical Cancer

Kabekkodu

Chakrabarty

Ghosh

et al. 2017

Public Health Genomics

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Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events. Recent studies have also mapped these epigenetic modification and pathways leading to carcinogenesis. Discovery of drugs that target proteins/enzymes in the epigenetic pathways may provide better therapeutic opportunities, and identification of such modulators for DNA methylation, histone modifications, and expression of noncoding RNAs for several cancer types is underway. In this review, we provide a detailed description of recent developments in the field of epigenetics and its impact on personalized medicine to manage cervical cancer.

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Epigenetic Regulation of Inflammatory Cytokines and Associated Genes in Human Malignancies

Cited by 102 publications

References 103 publications

RNF20 and histone H2B ubiquitylation exert opposing effects in Basal-Like versus luminal breast cancer

RNF20 and histone H2B ubiquitylation exert opposing effects in Basal-Like versus luminal breast cancer

Combined Effect of IL-12Rβ2 and IL-23R Expression on Prognosis of Patients with Laryngeal Cancer

Epigenomics, Pharmacoepigenomics, and Personalized Medicine in Cervical Cancer

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