Review
Oncology
Chen Li, Yan Wang, Yueqing Gong, Tengrui Zhang, Jiaqi Huang, Zhen Tan, Lixiang Xue
Summary: EZH2 inhibitors have shown anticancer activity by targeting EZH2, but resistance in some lymphomas and solid tumors calls for combination with other treatment modalities to enhance efficacy. Combining EZH2 inhibitors with therapies such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy has demonstrated complementary or synergistic antitumor effects.
CLINICAL EPIGENETICS
(2021)
Article
Biochemistry & Molecular Biology
Sarah Brunty, Kristeena Ray Wright, Brenda Mitchell, Nalini Santanam
Summary: Activation of trimethylation of histone 3 lysine 27 (H3K27me3) by EZH2 plays a role in endometriosis, with higher expression of PRC2 complex components like JARID2, miR-155, and FOXP3 noted in patient tissues. MiR-155 affects the PRC2 complex but has minimal impact on JARID2 expression, suggesting alternative pathways may be involved. A novel crosstalk between miR-155, the PRC2 complex, JARID2, and PHF19 has been identified, providing potential epigenetic targets for further study in endometriosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Michal Wozniak, Malgorzata Czyz
Summary: Melanoma is a deadly skin cancer that is increasing worldwide. EZH2 mutations have been found in melanoma and contribute to abnormal gene silencing. Recent evidence suggests that targeting the interaction between long non-coding RNAs (lncRNAs) and EZH2 may slow down the progression of melanoma. This review summarizes the involvement of lncRNAs in EZH2-mediated gene silencing in melanoma and discusses the potential of blocking lncRNA-EZH2 interaction as a novel therapeutic option.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Cell Biology
Shanshan Wang, Xuewen Xu, Yan Liu, Jianjun Jin, Feng Zhu, Wei Bai, Yubo Guo, Jiali Zhang, Hao Zuo, Zaiyan Xu, Bo Zuo
Summary: The study identified a novel EZH2-binding lincRNA, TCONS-00036665, which promotes pig skeletal satellite cell proliferation and inhibits cell differentiation. Mechanistic studies revealed that TCONS-00036665 interacts with EZH2 to repress target gene expression involved in pig myogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Mikolaj Filon, Joseph Gawdzik, Andrew Truong, Glenn Allen, Wei Huang, Tariq Khemees, Rehaan Machhi, Peter Lewis, Bing Yang, John Denu, David Jarrard
Summary: Histone modifications play a role in cancer progression. EZH2 and NSD2 expression and co-regulation were investigated in hormone-sensitive and castrate-resistant prostate cancer. Increased co-expression of EZH2 and NSD2 was found in castrate-resistant prostate cancer, metastatic tissues, and associated with shorter disease-free survival, highlighting their potential as therapeutic targets.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Pornpimol Phuengmaung, Phuriwat Khiewkamrop, Jiradej Makjaroen, Jiraphorn Issara-Amphorn, Atsadang Boonmee, Salisa Benjaskulluecha, Patcharee Ritprajak, Aleksandra Nita-Lazar, Tanapat Palaga, Nattiya Hirankarn, Asada Leelahavanichkul
Summary: The absence of Ezh2 in macrophages resulted in less severe sepsis, indicating the importance of Ezh2 in regulating the inflammatory response. Additionally, the use of an Ezh2 inhibitor might be beneficial in severe infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Areerat Kunanopparat, Asada Leelahavanichkul, Peerapat Visitchanakun, Patipark Kueanjinda, Pornpimol Phuengmaung, Kritsanawan Sae-khow, Atsadang Boonmee, Salisa Benjaskulluecha, Tanapat Palaga, Nattiya Hirankarn
Summary: The response of macrophages to LPS may determine the clinical manifestations of sepsis, while Ezh2 may interfere with this response. Results showed that Ezh2-deficient macrophages exhibited less severe LPS-induced inflammation and more severe LPS tolerance, partly due to the upregulation of Socs3.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Suzhen Zhang, Jun Liu, Feng Li, Mudan Yang, Junping Wang
Summary: KIF4A is significantly overexpressed in insulinoma and is associated with poor survival in pancreatic adenocarcinoma patients. Knocking down KIF4A inhibits the growth and metastasis of insulinoma cells. Mechanistically, reduced H3K27me3 modifications in KIF4A promoter sequences, as well as decreased expression of EZH2, promote KIF4A expression and contribute to insulinoma development.
Article
Medicine, Research & Experimental
Yan Jiang, Chan Xiang, Fan Zhong, Yang Zhang, Liyan Wang, Yuanyuan Zhao, Jiucun Wang, Chen Ding, Li Jin, Fuchu He, Haijian Wang
Summary: In this study, it was found that EZH2 and JMJD3 antagonistically modulate HSCs activation. The therapeutic effects of DZNep as an epigenetic drug in liver fibrosis are associated with the regulation of EZH2 towards direct target genes encoding TGF-I31 pseudoreceptor BAMBI, anti-inflammatory cytokine IL10 and cell cycle regulators CDKN1A, GADD45A and GADD45B, which are also regulated by JMJD3. This study provides new mechanistic insight into the epigenetic modulation of EZH2 and JMJD3 in HSCs biology and hepatic fibrogenesis.
Review
Medicine, General & Internal
Haixia Wang
Summary: Obesity is a major public health issue worldwide and is associated with excessive accumulation of adiposity, metabolic disorders, and cancer susceptibility. Recent studies have shown that not only genetic variants but also epigenetic predisposition contribute to the intrinsic risk of obesity. EZH2 plays an important role in adipogenesis and obesity.
Article
Oncology
Jose Diaz-Chavez, Olga Gutierrez-Hernandez, Lucia Taja-Chayeb, Sindy Gutierrez-Chavarria, Alejandro Aviles-Salas, Myrna Candelaria
Summary: The study demonstrates the utility of using ctDNA to search for EZH2 mutations in diffuse large B-cell lymphoma, highlighting the importance of studying this gene and the potential effectiveness of targeted therapy in patients with activating mutations in EZH2.
Article
Oncology
Lennart Versemann, Shilpa Patil, Benjamin Steuber, Zhe Zhang, Waltraut Kopp, Hannah Elisa Krawczyk, Silke Kaulfuss, Bernd Wollnik, Philipp Stroebel, Albrecht Neesse, Shiv K. Singh, Volker Ellenrieder, Elisabeth Hessmann
Summary: Epigenetic alterations contribute to the aggressiveness and therapy resistance of Pancreatic Ductal Adenocarcinoma (PDAC). In this study, the authors aimed to explore the molecular prerequisites and underlying mechanisms of oncogenic EZH2 activity in PDAC progression. They found that the TP53 status critically determines oncogenic EZH2 activity in PDAC, with EZH2 blockade only being effective in TP53-wildtype PDAC subtypes. Mechanistically, EZH2 depletion increases p53wt stability by de-repressing CDKN2A. These findings highlight the significance of molecular stratification and the CDKN2A-p53wt axis for successful epigenetic targeting in PDAC.
Article
Biochemistry & Molecular Biology
Julian Aldana, Miranda L. L. Gardner, Michael A. A. Freitas
Summary: A comprehensive multi-omics approach was used to study the effects of differential H3K27me3 deposition driven by EZH2 mutations. The study identified pathways involved in cellular proliferation, differentiation, and migration that are impacted by EZH2 GOF and LOF mutants. The results shed light on EZH2-mediated cell transformative processes from the epigenetic to the phenotypic level, providing insights for improved diagnostics and treatment in hematologic malignancies with mutated EZH2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Fan Chen, Aria L. L. Byrd, Jinpeng Liu, Robert M. M. Flight, Tanner J. J. DuCote, Kassandra J. J. Naughton, Xiulong Song, Abigail R. R. Edgin, Alexsandr Lukyanchuk, Danielle T. T. Dixon, Christian M. M. Gosser, Dave-Preston Esoe, Rani D. D. Jayswal, Stuart H. H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson
Summary: The impact of EZH2 deficiency on KRAS-driven lung adenocarcinomas was studied, and it was found that haplo-insufficiency and full-insufficiency of EZH2 have divergent effects. Tumors with EZH2 haplo-insufficiency were less lethal and lower grade compared to tumors with EZH2 full-insufficiency. Three-dimensional cultures were used to explore epigenetic drug sensitivities for cancer.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Landon C. Brown, Susan Halabi, Jason A. Somarelli, Michael Humeniuk, Yuan Wu, Taofik Oyekunle, Lauren Howard, Jiaoti Huang, Monika Anand, Catrin Davies, Prekshaben Patel, Janet Staats, Kent J. Weinhold, Michael R. Harrison, Tian Zhang, Daniel J. George, Andrew J. Armstrong
Summary: Immunotherapy with avelumab showed poor efficacy in men with progressive neuroendocrine or aggressive-variant metastatic prostate cancer, but potential mechanisms for immune activation were identified in an extraordinary responder.
PROSTATE CANCER AND PROSTATIC DISEASES
(2022)