EZH2 suppresses endogenous retroviruses and an interferon response in cancers

Jayabal, Panneerselvam; Ma, Xiuye; Shiio, Yuzuru

doi:10.18632/genesandcancer.218

Cited by 9 publications

(4 citation statements)

References 28 publications

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“…Notably, separating tumors by HSATII expression revealed significantly shorter overall survival of patients with HSATII-high tumors (Figure 4D). Taken together, this work shows that repeats are a diverse set of RNA species; some are associated with tumor cell IFN response (9,10,12,13,27,28), while others, such as SAT repeats, are associated with EMT and low IFN signaling that is typically seen in more aggressive tumors.…”

Section: Sat Repeat Rna Expression Is Linked With An Immunosuppressiv...mentioning

confidence: 70%

Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype

Porter¹,

Sun²,

Flores³

et al. 2022

Journal of Clinical Investigation

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Aberrant expression of viral-like repeat elements is a common feature of epithelial cancers, and the substantial diversity of repeat species provides a distinct view of the cancer transcriptome. Repeatome profiling across ovarian, pancreatic, and colorectal cell lines identifies distinct clustering independent of tissue origin that is seen with coding gene analysis. Deeper analysis of ovarian cancer cell lines demonstrated that human satellite II (HSATII) satellite repeat expression was highly associated with epithelial-mesenchymal transition (EMT) and anticorrelated with IFN-response genes indicative of a more aggressive phenotype. SATII expression — and its correlation with EMT and anticorrelation with IFN-response genes — was also found in ovarian cancer RNA-Seq data and was associated with significantly shorter survival in a second independent cohort of patients with ovarian cancer. Repeat RNAs were enriched in tumor-derived extracellular vesicles capable of stimulating monocyte-derived macrophages, demonstrating a mechanism that alters the tumor microenvironment with these viral-like sequences. Targeting of HSATII with antisense locked nucleic acids stimulated IFN response and induced MHC I expression in ovarian cancer cell lines, highlighting a potential strategy of modulating the repeatome to reestablish antitumor cell immune surveillance.

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Section: Sat Repeat Rna Expression Is Linked With An Immunosuppressiv...mentioning

confidence: 70%

Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype

Porter¹,

Sun²,

Flores³

et al. 2022

Journal of Clinical Investigation

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“…These six genes have been extensively studied in the context of human diseases. NELL2 is a neuron-specific secretory protein widely involved in various disease processes [ 21 , 22 ], and interference with NELL2 inhibits the interferon-beta (IFN-β) response [ 21 ]. The COL12A1 gene is associated with multiple disease prognoses and immune infiltration, and high COL12A1 expression in cancer tissues can promote disease development and progression [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated Proteotranscriptomics Reveals Differences in Molecular Immunity between Min and Large White Pig Breeds

Yang

Liu

Huang

et al. 2022

Biology

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Long-term selection or evolution is an important factor governing the development of disease resistance in pigs. To better clarify the molecular mechanisms underlying different levels of disease resistance, we used transcriptomics and proteomics analysis to characterize differences in the immunities between six resistant (Min pig) and six susceptible (Large White, LW) pigs which were raised in the same environment. A total of 135 proteins and 791 genes were identified as being differentially expressed between the Large White and Min pig groups. Protein expression clustering and functional analysis revealed that proteins related to immune system process, humoral immune response, the B cell receptor signaling pathway, lymphocyte-mediated immunity, and innate immune responses were more highly expressed in Min pigs. Transcriptome gene set enrichment analysis was used to reveal that pathways of cell adhesion molecules and antigen processing and presentation are significantly enriched in Min pigs. Integrated proteomics and transcriptomics data analysis identified 16 genes that are differentially expressed at both the mRNA and protein levels. In addition, 13 out of these 16 genes were related to the quantitative trait loci of immune diseases, including neural EGFL-like 2 (NELL2) and lactate dehydrogenase B (LDHB), which are involved in innate immunity. Correlation analysis between the genes/proteins and cytokines shows upregulated proteins in LW pigs in association with immunosuppressive/pro-inflammatory cytokines, such as interleukin (IL) 10, IL6, and tumor necrosis factor alpha. This was further validated using parallel reaction monitoring analysis. In summary, we discovered several potential candidate pathways and key genes/proteins involved in determining differences in disease resistance between the two studied pig breeds, which could provide new insights into the breeding of pigs for disease resistance.

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“…We therefore compared three different cultivation settings commonly used for RB cell cultures [ 3 , 5 , 6 , 7 , 8 ] in order to identify differences in morphology, growth and gene expression patterns. We could show that RB morphology is not affected by the culture conditions analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…Thirty-five percent of RB patients develop secondary tumors and 50% of these patients die after therapy [ 4 ].Therefore, reliable in vitro and in vivo systems are indispensable for studying RB tumor biology in order to develop new treatment strategies for an optimization of RB management. However, different cultivation protocols for the same RB cell lines have been published so far [ 3 , 5 , 6 , 7 , 8 ]. It is well-known that varying cell culture conditions, e.g., using different media and/or supplements as well as different CO 2 concentrations, have a huge impact on the tumor cell growth, viability and gene expression, e.g., of epithelial-mesenchymal transition (EMT) markers.…”

Section: Introductionmentioning

confidence: 99%

Retinoblastoma Cell Growth In Vitro and Tumor Formation In Ovo—Influence of Different Culture Conditions

Doege

Steens

Dünker

et al. 2022

MPs

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Retinoblastoma (RB) is a primary intraocular malignancy in childhood. Relapses may develop and cause secondary cancers during later development. This study was set up to identify optimal cell culture conditions for RB cell growth in vitro and to optimize tumor growth in an in vivo model. RB cell lines (Y79 and WERI-Rb1) were cultivated under three different in vitro conditions and apoptosis, proliferation and cell growth, as well as expression profiles of two epithelial-mesenchymal transition (EMT) markers, were analyzed. EMT gene expression profiles were not generally changed, whereas apoptosis levels, tumor cell proliferation, and in vitro growth were significantly influenced by different cell culture conditions. In order to optimize the time-limited chick chorioallantoic membrane (CAM) assay, we investigated two different time points of tumor cell inoculation (embryonic development day EDD8 and EDD10) as well as three different cell concentrations. We showed that inoculation at EDD8 led to decreased tumor formation and chicken viability, whereas different cell concentrations did not change size and weight of developing tumors. Our findings demonstrate that medium conditions in vitro as well as the starting point for CAM inoculation in ovo significantly influence the experimental outcome of investigations using RB cell lines.

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EZH2 suppresses endogenous retroviruses and an interferon response in cancers

Cited by 9 publications

References 28 publications

Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype

Satellite repeat RNA expression in epithelial ovarian cancer associates with a tumor-immunosuppressive phenotype

Integrated Proteotranscriptomics Reveals Differences in Molecular Immunity between Min and Large White Pig Breeds

Retinoblastoma Cell Growth In Vitro and Tumor Formation In Ovo—Influence of Different Culture Conditions

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