Article
Biochemistry & Molecular Biology
Yang Yi, Yanqiang Li, Chao Li, Longxiang Wu, Dongyu Zhao, Fuxi Li, Ladan Fazli, Rui Wang, Long Wang, Xuesen Dong, Wei Zhao, Kaifu Chen, Qi Cao
Summary: CDCA8 overexpression is associated with poor clinical outcome in patients with prostate cancer, and EZH2 is responsible for CDCA8 activation in PCa.
Article
Biochemistry & Molecular Biology
Xufen Yu, Jun Wang, Weida Gong, Anqi Ma, Yudao Shen, Chengwei Zhang, Xijuan Liu, Ling Cai, Jing Liu, Gang Greg Wang, Jian Jin
Summary: This passage focuses on the noncanonical function of EZH2 in the development of multiple myeloma (MM), and proposes a novel therapeutic strategy, pharmacological degradation of EZH2, for treating EZH2-dependent MM.
Article
Biochemistry & Molecular Biology
Husheng Mei, Hong Wu, Jing Yang, Bin Zhou, Aoli Wang, Chen Hu, Shuang Qi, Zongru Jiang, Fengming Zou, Beilei Wang, Feiyang Liu, Yongfei Chen, Wenchao Wang, Jing Liu, Qingsong Liu
Summary: Enhancer of zeste homolog 2 (EZH2), as an enzymatic subunit of the PRC2 complex, plays a crucial role in tumor development and has gained research interest as a potential therapeutic target. Overexpression or mutations of EZH2 have been associated with tumor cell proliferation in TNBC and DLBCL. Current EZH2 inhibitors have shown promise but resistance can occur due to noncatalytic or transcriptional activity. Researchers have discovered a new irreversible EZH2 inhibitor, IHMT-337, which degrades EZH2 and inhibits cell proliferation in TNBC and DLBCL models in vitro and in vivo. This finding suggests that destroying EZH2 in addition to enzymatic inhibition may be a promising therapeutic strategy.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Oncology
Min Gao, Yongwen Li, Peijun Cao, Hongyu Liu, Jun Chen, Shirong Kang
Summary: This paper reviews the importance of PRC2 in the development and progression of lung cancer, and explores its role in tumor immunity, cellular behavior regulation, and drug treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Medicinal
Yajie Shi, Qiuyue Zhang, Maoying Zhang, Yongsong Chen, Jianwen Sun, Lu Chen, Sen Liu, Zhongbo Liu, Jingyu Yang, Chunfu Wu, Zhonghui Zheng, Lihui Wang, Guoliang Chen
Summary: In recent years, the dual inhibition of G9a and EZH2 has emerged as a promising strategy for cancer treatment. This study introduces the discovery of G9a/EZH2 dual inhibitors that combine the pharmacophores of G9a and EZH2 inhibitors. Among them, compound 15h demonstrates potent inhibitory activities against G9a and EZH2, as well as superior antiproliferative effects on RD and SW982 cell lines. In a xenograft mouse model, 15h exhibits significant antitumor efficacy against human rhabdoid tumor, with an inhibitory rate of 86.6%, without causing observable toxic effects. The results suggest that 15h is a potential candidate for the treatment of malignant rhabdoid tumor.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Juyeon Seo, Minsu Park, Dongmi Ko, Seongjae Kim, Jung Min Park, Soeun Park, Kee Dal Nam, Lee Farrand, Jinsol Yang, Chaok Seok, Eunsun Jung, Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo
Summary: We investigated the effectiveness of the second-generation antihistamine ebastine (EBA) in suppressing breast cancer stem cells (BCSCs) in triple-negative breast cancer (TNBC). Our findings demonstrate that EBA can inhibit the FAK-mediated JAK2/STAT3 and MEK/ERK signaling pathways by binding to FAK's tyrosine kinase domain. Furthermore, EBA treatment induces apoptosis and reduces the expression of BCSC markers, suggesting its potential in targeting BCSC-like cell populations and reducing tumor bulk. In vivo, EBA administration significantly impedes BCSC-enriched tumor burden, angiogenesis, and distant metastasis. These results highlight the potential of EBA as a therapeutic agent for treating TNBC by simultaneously targeting JAK2/STAT3 and MEK/ERK pathways. Further investigation of EBA as an anti-metastatic agent for TNBC is warranted.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Cell Biology
Yu Wang, Liming Zhu, Mei Guo, Gang Sun, Kun Zhou, Wenjing Pang, Dachun Cao, Xin Tang, Xiangjun Meng
Summary: The study demonstrated that WHSC1 plays a crucial role in regulating tumorigenesis and chemosensitivity in colorectal cancer through histone modification. Reduction of WHSC1 enhances apoptosis in colon cancer cells and improves chemosensitivity. Targeting WHSC1 and H3K36me2 modification could potentially disrupt CRC progression and overcome chemotherapeutic resistance.
CELL DEATH DISCOVERY
(2021)
Review
Pharmacology & Pharmacy
Cinzia Lanzi, Noemi Arrighetti, Sandro Pasquali, Giuliana Cassinelli
Summary: Soft tissue sarcomas (STSs) are rare mesenchymal malignancies characterized by distinctive molecular, histological, and clinical features. Underlying chromatin deregulation plays a major role in the development of STSs. The antagonistic interaction between BAFs and PRCs has been identified as a potential target for therapeutic intervention in certain types of STSs, such as epithelioid sarcoma (ES), extracranial extrarenal malignant rhabdoid tumors (eMRTs), and synovial sarcoma (SS).
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Wei Zhang, Xianghui Fu, Jiansheng Xie, Hongming Pan, Weidong Han, Wendong Huang
Summary: miR-26a suppresses intestinal inflammatory response by reducing NF-kB/STAT3 activation and IL-6 production, and potentially serves as a novel therapeutic target for CAC. NF-kB regulators including TLR3, PTEN, and PKCd are identified as potential targets of miR-26a.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Chemistry, Medicinal
Jia Zeng, Jifa Zhang, Ying Sun, Jiaxing Wang, Changyu Ren, Souvik Banerjee, Liang Ouyang, Yuxi Wang
Summary: This article reviews the structure and biological functions of the EZH2 protein, as well as its relationship with various diseases. It also provides an overview of the current development of specific inhibitors for EZH2, and highlights the latest progress in new strategies such as drug combination, dual-target inhibitors, targeted protein degradation technology, and protein-protein interaction inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Maria E. Gonzalez, Giuseppina Daniela Naimo, Talha Anwar, Alessandro Paoli, Shilpa R. Tekula, Suny Kim, Natasha Medhora, Shoshana A. Leflein, Jacob Itkin, Raymond Trievel, Kelley M. Kidwell, Yu-Chih Chen, Loredana Mauro, Euisik Yoon, Sebastiano Ando, Celina G. Kleer
Summary: This study uncovers the non-canonical function of EZH2 in promoting TNBC metastasis through phosphorylation at T367. It also reveals the ability of cytosolic EZH2 to methylate p38 alpha, enhancing its stability. Dual inhibition of EZH2 methyltransferase and p38 kinase activities can reduce TNBC growth and metastasis.
Review
Medicine, Research & Experimental
Mahshid Deldar Abad Paskeh, Atefeh Mehrabi, Mohammad Hossein Gholami, Amirhossein Zabolian, Ehsan Ranjbar, Hossein Saleki, Adnan Ranjbar, Mehrdad Hashemi, Yavuz Nuri Ertas, Kiavash Hushmandi, Sepideh Mirzaei, Milad Ashrafizadeh, Ali Zarrabi, Saeed Samarghandian
Summary: EZH2 plays a crucial role in brain tumors, promoting the proliferation and invasion of cancer cells while demonstrating tumor-suppressor activity in medulloblastoma. In addition to regulating gene expression, EZH2 can also influence the response of brain tumors to chemotherapy and radiotherapy.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Amira Fitieh, Andrew J. Locke, Mobina Motamedi, Ismail Hassan Ismail
Summary: Polycomb group proteins play roles in stem cell maintenance, gene silencing, and DNA damage repair. BMI1, a member of PRC1, is involved in DNA repair and genome integrity, making it a potential pharmacological target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nanoscience & Nanotechnology
Konika Choudhury, Arun Chattopadhyay, Siddhartha Sankar Ghosh
Summary: This study successfully targeted lung adenocarcinoma cells by loading levocetirizine into copper nanoclusters and then loading them into mannose functionalized chitosan nanoparticles. The as-synthesized nanocomposites showed promising anticancer activity and pH-dependent drug release.
ACS APPLIED NANO MATERIALS
(2023)
Article
Cell Biology
Liping Chu, Yuxiu Qu, Yang An, Linjun Hou, Juewan Li, Weijia Li, Gaofeng Fan, Bao-Liang Song, En Li, Liye Zhang, Wei Qi
Summary: This study investigates the pharmacological mechanism of the PRC2 inhibitor MAK683 and identifies a group of senescence-associated genes that are derepressed upon PRC2 inhibition, leading to tumor regression and improved therapeutic efficacy. Furthermore, the combination of PRC2 inhibitors and CDK4/6 inhibitors shows even better effects, providing a novel strategy for clinical treatment.
CELL DEATH & DISEASE
(2022)
Article
Genetics & Heredity
Guangyu Wang, Ana Sofia Cruz, Keith Youker, Hernan G. Marcos-Abdala, Rajarajan A. Thandavarayan, John P. Cooke, Guillermo Torre-Amione, Kaifu Chen, Arvind Bhimaraj
Summary: The transition between endothelial and mesenchymal cell types plays a key role in the pathophysiology of heart failure and subsequent recovery, as observed in both murine models and human myocardial samples.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Guangyu Wang, Bo Xia, Man Zhou, Jie Lv, Dongyu Zhao, Yanqiang Li, Yiwen Bu, Xin Wang, John P. Cooke, Qi Cao, Min Gyu Lee, Lili Zhang, Kaifu Chen
Summary: The study explores the role of MACMIC analysis in identifying feature pairs with maximal colocalization and minimal correlation in the epigenomic landscape. It reveals a dual role of CTCF in epigenetic regulation of cell identity genes.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ting-You Wang, Qi Liu, Yanan Ren, Sk Kayum Alam, Li Wang, Zhu Zhu, Luke H. Hoeppner, Scott M. Dehm, Qi Cao, Rendong Yang
Summary: Exitron splicing (EIS) functions in cancer by affecting 63% of human coding genes, 95% of which are tumor specific. EIS alters cancer driver genes, leading to gain- or loss-of-function, and also produces neoepitopes that bind to MHC class I or II. Analysis of clinical data shows a correlation between EIS-derived neoantigen load and checkpoint inhibitor response in clear cell renal cell carcinoma.
Article
Cell Biology
Yang Yi, Yanqiang Li, Qingshu Meng, Qiaqia Li, Fuxi Li, Bing Lu, Jiangchuan Shen, Ladan Fazli, Dongyu Zhao, Chao Li, Weihua Jiang, Rui Wang, Qipeng Liu, Aileen Szczepanski, Qianru Li, Wei Qin, Adam B. Weiner, Tamara L. Lotan, Zhe Ji, Sundeep Kalantry, Lu Wang, Edward M. Schaeffer, Hengyao Niu, Xuesen Dong, Wei Zhao, Kaifu Chen, Qi Cao
Summary: EZH2 functions in cancer-related translational regulation by enhancing rRNA 2'-O methylation through interaction with FBL, facilitating C/D box small nucleolar ribonucleoprotein assembly, and impairing translation initiation in cancer cells.
NATURE CELL BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Anahita Mojiri, Brandon K. Walther, Chongming Jiang, Gianfranco Matrone, Rhonda Holgate, Qiu Xu, Elisa Morales, Guangyu Wang, Jianhua Gu, Rongfu Wang, John P. Cooke
Summary: The study on a unique HGPS cell model demonstrated the impact of telomere repair on vascular cell aging, suggesting telomerase mRNA as a potential effective therapeutic approach for HGPS. Research on endothelial cells differentiated from patients with HGPS showed that hTERT treatment improved cellular function, restored endothelial function, and reduced the release of inflammatory markers.
EUROPEAN HEART JOURNAL
(2021)
Article
Oncology
Andrea Loehr, Akash Patnaik, David Campbell, Jeremy Shapiro, Alan H. Bryce, Ray McDermott, Brieuc Sautois, Nicholas J. Vogelzang, Richard M. Bambury, Eric Voog, Jingsong Zhang, Josep M. Piulats, Arif Hussain, Charles J. Ryan, Axel S. Merseburger, Gedske Daugaard, Axel Heidenreich, Karim Fizazi, Celestia S. Higano, Laurence E. Krieger, Cora N. Sternberg, Simon P. Watkins, Darrin Despain, Andrew D. Simmons, Melanie Dowson, Tony Golsorkhi, Simon Chowdhury, Wassim Abida
Summary: The study showed that plasma, tissue, and local testing of mCRPC patients can effectively identify men with BRCA(+) mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yang Yi, Yanqiang Li, Chao Li, Longxiang Wu, Dongyu Zhao, Fuxi Li, Ladan Fazli, Rui Wang, Long Wang, Xuesen Dong, Wei Zhao, Kaifu Chen, Qi Cao
Summary: CDCA8 overexpression is associated with poor clinical outcome in patients with prostate cancer, and EZH2 is responsible for CDCA8 activation in PCa.
Article
Oncology
Brian W. Labadie, David S. Morris, Alan H. Bryce, Robert Given, Jingsong Zhang, Wassim Abida, Simon Chowdhury, Akash Patnaik
Summary: This article summarizes the safety data of the PARP inhibitor rucaparib for the treatment of metastatic castration-resistant prostate cancer and provides guidelines for managing treatment-emergent adverse events. The study found that the adverse events observed with rucaparib were consistent with other PARP inhibitors, with gastrointestinal events, asthenia/fatigue, and anemia being the most common. Most adverse events were self-limiting and did not require treatment modification or interruption.
CANCER MANAGEMENT AND RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Dongyu Zhao, Min Zhang, Shaodong Huang, Qi Liu, Sen Zhu, Yanqiang Li, Weihua Jiang, Daniel L. Kiss, Qi Cao, Lili Zhang, Kaifu Chen
Summary: In this study, elevated expression of CHD6 in prostate cancer is found to be associated with poor prognosis. CHD6 regulates the oncogenicity of prostate cancer cells by evicting nucleosomes and activating prostate cancer pathways.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Krishan Gupta, Guangyu Wang, Shuo Zhang, Xinlei Gao, Rongbin Zheng, Yanchun Zhang, Qingshu Meng, Lili Zhang, Qi Cao, Kaifu Chen
Summary: Recent studies have found stripes as architectural features of three-dimensional chromatin and their connection to epigenetic regulation of transcription. While there are tools available to define stripes in a single sample, there is no reported method to quantitatively measure the dynamic change of each stripe between samples. In this study, a bioinformatics tool called StripeDiff was developed to detect differential stripes between samples. StripeDiff showed optimal performance in both simulation data analysis and real Hi-C data analysis. Applying StripeDiff to Hi-C data revealed new insights into the connection between change of chromatin stripe and change of chromatin modification, transcriptional regulation, and cell differentiation.
Article
Oncology
Brian M. Olson, Kiranj Chaudagar, Riyue Bao, Sweta Sharma Saha, Christina Hong, Marguerite Li, Srikrishnan Rameshbabu, Raymond Chen, Alison Thomas, Akash Patnaik
Summary: Retinoblastoma loss-of-function (LOF) can lead to non-T-cell-inflamed immunologically cold tumor microenvironments, reducing the responsiveness to immune checkpoint blockade. Inhibiting BET domain and extraterminal (BET) protein can reprogram the tumor microenvironment, increasing T-cell infiltration and enhancing the sensitivity of Rb-deficient prostate cancer to immune checkpoint blockade.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Biotechnology & Applied Microbiology
Shengyu Li, Pengzhi Zhang, Weiqing Chen, Lingqun Ye, Kristopher W. Brannan, Nhat-Tu Le, Jun-ichi Abe, John P. Cooke, Guangyu Wang
Summary: RNA velocity offers a method to infer cell state transitions from single-cell RNA sequencing data. cellDancer is a scalable deep neural network that locally infers velocity for each cell and provides single-cell resolution inference of velocity kinetics. It shows robust performance in multiple kinetic regimes, high dropout ratio datasets, and sparse datasets. Additionally, cellDancer provides cell-specific predictions of transcription, splicing, and degradation rates, which are potential indicators of cell fate.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xinlei Gao, Yang Yi, Jie Lv, Yanqiang Li, Kulandaisamy Arulsamy, Sahana Suresh Babu, Ivone Bruno, Lili Zhang, Qi Cao, Kaifu Chen
Summary: RNA expression of a gene is influenced by both transcriptional and post-transcriptional regulation, including RNA decay and m6A modification. Tumor suppressor RNAs tend to decay faster and have preferential deposition of m6A modification. In prostate cancer cells, there is increased abundance of m6A and faster decay of tumor suppressor RNAs. Knockdown of m6A methyltransferase METTL3 and reader YTHDF2 affects tumor suppressor RNAs more significantly.
NUCLEIC ACIDS RESEARCH
(2023)