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https://www.readbyqxmd.com/read/29468525/valproic-acid-promotes-apoptosis-and-cisplatin-sensitivity-through-downregulation-of-h19-noncoding-rna-in-ovarian-a2780-cells
#1
Zahre Sajadpoor, Zeinab Amini-Farsani, Hossein Teimori, Mehdi Shamsara, Mohammad Hossein Sangtarash, Payam Ghasemi-Dehkordi, Farrokh Yadollahi
Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a lncRNA involving in cisplatin resistance in cancers. Valproic acid (VPA) is a commonly used drug for clinical treatment of seizure disorders. In addition, this drug may display its effects through regulation of noncoding RNAs controlling gene expression. The aim of the present study was the investigation of VPA treatment effect on H19 expression in ovarian cancer cells and also the relation of the H19 levels with apoptosis and cisplatin resistance...
February 22, 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29467191/targeted-next-generation-sequencing-in-blast-phase-myeloproliferative-neoplasms
#2
Terra L Lasho, Mythri Mudireddy, Christy M Finke, Curtis A Hanson, Rhett P Ketterling, Natasha Szuber, Kebede H Begna, Mrinal M Patnaik, Naseema Gangat, Animesh Pardanani, Ayalew Tefferi
Among 248 consecutive patients with blast phase myeloproliferative neoplasm (MPN-BP), DNA collected at the time of blast transformation was available in 75 patients (median age, 66 years; 64% men). MPN-BP followed primary myelofibrosis in 39 patients, essential thrombocythemia in 20 patients, and polycythemia vera in 16 patients. A myeloid neoplasm-relevant 33-gene panel was used for next-generation sequencing. Driver mutation distribution was JAK2 57%, CALR 20%, MPL 9%, and triple-negative 13%. Sixty-four patients (85%) harbored other mutations/variants, including 37% with ≥3 mutations; most frequent were ASXL1 47%, TET2 19%, RUNX1 17%, TP53 16%, EZH2 15%, and SRSF2 13%; relative mutual exclusivity was expressed by TP53 , EZH2 , LNK , RUNX1 , SRSF2 , and NRAS/KRAS mutations...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29466876/srebp2-contributes-to-cisplatin-resistance-in-ovarian-cancer-cells
#3
Lei Zheng, Li Li, Yun Lu, Fangfang Jiang, Xiu-An Yang
This study is to investigate transcription factors involved in cisplatin resistance in ovarian cancer cells. The transcriptome of cisplatin resistant and sensitive A2780 epithelial ovarian cancer cells was obtained from GSE15372. Ovarian transcriptome data GSE62944 was downloaded from TCGA and applied for transcription regulatory network analysis. The analysis results were confirmed using quantitative polymerase chain reaction. The roles of SREBP2 in cisplatin-resistant cells were investigated by RNA inference and cell viability analysis...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29466371/ezh2-is-not-required-for-cardiac-regeneration-in-neonatal-mice
#4
Abdalla Ahmed, Tao Wang, Paul Delgado-Olguin
The neonatal mouse heart has the remarkable capacity to regenerate lost myocardium within the first week of life. Neonatal cardiomyocytes re-express fetal genes that control cell proliferation after injury to promote regeneration. The loss of regenerative capacity of the heart one week after birth coincides with repression of a fetal transcriptional program coordinated by epigenetic regulators. The histone methyltransferase enhancer of zeste homolog 2 (Ezh2) is a repressor of fetal cardiac transcriptional programs and suppresses cardiomyocyte cell proliferation, suggesting a potential function in heart regeneration...
2018: PloS One
https://www.readbyqxmd.com/read/29465369/altered-gene-expression-profiles-of-histone-lysine-methyltransferases-and-demethylases-in-rheumatoid-arthritis-synovial-fibroblasts
#5
Yasuto Araki, Yoshimi Aizaki, Kojiro Sato, Hiromi Oda, Riki Kurokawa, Toshihide Mimura
OBJECTIVES: Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs. METHODS: SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement...
January 31, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29456795/discovery-of-ebi-2511-a-highly-potent-and-orally-active-ezh2-inhibitor-for-the-treatment-of-non-hodgkin-s-lymphoma
#6
Biao Lu, Xiaodong Shen, Lei Zhang, Dong Liu, Caihua Zhang, Jingsong Cao, Ru Shen, Jiayin Zhang, Dan Wang, Hong Wan, Zhibin Xu, Ming-Hsun Ho, Minsheng Zhang, Lianshan Zhang, Feng He, Weikang Tao
A novel series of benzofuran derived EZH2 inhibitors were discovered through a scaffold hopping approach based on the clinical compound of EPZ-6438. Further rational structure-activity relationship exploration and optimization led to the discovery of more potent EZH2 inhibitors with oral bioavailability in mice and rats. A lead compound EBI-2511 (compound 34 ) demonstrated excellent in vivo efficacy in Pfeiffer tumor Xenograft models in mouse and is under preclinical development for the treatment of cancers associated with EZH2 mutations...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29447387/ezh2-promotes-clock-function-and-hematopoiesis-independent-of-histone-methyltransferase-activity-in-zebrafish
#7
Yingbin Zhong, Qiang Ye, Chengyan Chen, Mingyong Wang, Han Wang
EZH2 is a subunit of polycomb repressive complex 2 (PRC2) that silences gene transcription via H3K27me3 and was shown to be essential for mammalian liver circadian regulation and hematopoiesis through gene silencing. Much less, however, is known about how Ezh2 acts in live zebrafish. Here, we show that zebrafish ezh2 is regulated directly by the circadian clock via both E-box and RORE motif, while core circadian clock genes per1a, per1b, cry1aa and cry1ab are down-regulated in ezh2 null mutant and ezh2 morphant zebrafish, and either knockdown or overexpression of ezh2 alters locomotor rhythms, indicating that Ezh2 is required for zebrafish circadian regulation...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29445179/long-noncoding-rna-gas5-promotes-bladder-cancer-cells-apoptosis-through-inhibiting-ezh2-transcription
#8
Miao Wang, Chen Guo, Liang Wang, Gang Luo, Chao Huang, Yawei Li, Dong Liu, Fuqing Zeng, Guosong Jiang, Xingyuan Xiao
Aberrant expression of long noncoding RNA GAS5 in bladder cancer (BC) cells was identified in recent studies. However, the regulatory functions and underlying molecular mechanisms of GAS5 in BC development remain unclear. Here, we confirmed that there was a negative correlation between GAS5 level and bladder tumor clinical stage. Functionally, overexpression of GAS5 reduced cell viability and induced cell apoptosis in T24 and EJ bladder cancer cells. Mechanistically, GAS5 effectively repressed EZH2 transcription by directly interacting with E2F4 and recruiting E2F4 to EZH2 promoter...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445149/let-7c-inhibits-cholangiocarcinoma-growth-but-promotes-tumor-cell-invasion-and-growth-at-extrahepatic-sites
#9
Yu Xie, Hang Zhang, Xing-Jun Guo, Ye-Chen Feng, Rui-Zhi He, Xu Li, Shuo Yu, Yan Zhao, Ming Shen, Feng Zhu, Xin Wang, Min Wang, Asha Balakrishnan, Michael Ott, Feng Peng, Ren-Yi Qin
Cholangiocarcinoma (CCA) is a cancer type with high postoperative relapse rates and poor long-term survival largely due to tumor invasion, distant metastasis, and multidrug resistance. Deregulated microRNAs (miRNAs) are implicated in several cancer types including CCA. The specific roles of the miRNA let-7c in cholangiocarcinoma are not known and need to be further elucidated. In our translational study we show that microRNA let-7c expression was significantly downregulated in human cholangiocarcinoma tissues when compared to adjacent tissues of the same patient...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29438697/ezh2-and-runx1-mutations-collaborate-to-initiate-lympho-myeloid-leukemia-in-early-thymic-progenitors
#10
Christopher A G Booth, Nikolaos Barkas, Wen Hao Neo, Hanane Boukarabila, Elizabeth J Soilleux, George Giotopoulos, Noushin Farnoud, Alice Giustacchini, Neil Ashley, Joana Carrelha, Lauren Jamieson, Deborah Atkinson, Tiphaine Bouriez-Jones, Rab K Prinjha, Thomas A Milne, David T Teachey, Elli Papaemmanuil, Brian J P Huntly, Sten Eirik W Jacobsen, Adam J Mead
Lympho-myeloid restricted early thymic progenitors (ETPs) are postulated to be the cell of origin for ETP leukemias, a therapy-resistant leukemia associated with frequent co-occurrence of EZH2 and RUNX1 inactivating mutations, and constitutively activating signaling pathway mutations. In a mouse model, we demonstrate that Ezh2 and Runx1 inactivation targeted to early lymphoid progenitors causes a marked expansion of pre-leukemic ETPs, showing transcriptional signatures characteristic of ETP leukemia. Addition of a RAS-signaling pathway mutation (Flt3-ITD) results in an aggressive leukemia co-expressing myeloid and lymphoid genes, which can be established and propagated in vivo by the expanded ETPs...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#11
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29435158/osteopontin-integrin-engagement-induces-hif-1%C3%AE-tcf12-mediated-endothelial-mesenchymal-transition-to-exacerbate-colorectal-cancer
#12
Chi-Shuan Fan, Wei-Shone Chen, Li-Li Chen, Chia-Chi Chen, Yu-Ting Hsu, Kee Voon Chua, Horng-Dar Wang, Tze-Sing Huang
Osteopontin (OPN) is a multi-functional phospho-glycoprotein that can stimulate angiogenesis through acting on endothelial cells. As angiogenic sprouting involves endothelial-to-mesenchymal transition (EndoMT), we are intrigued to know whether OPN exerts an effect on EndoMT. Clinically, we indeed detected EndoMT-derived cells next to OPN-expressing cells in colorectal cancer tissues. Furthermore, we treated OPN to primary cultures of endothelial cells to investigate the EndoMT-inducing activity and the underlying mechanisms...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435063/inhibition-of-enhancer-of-zeste-homolog-2-increases-the-expression-of-p16-and-suppresses-the-proliferation-and-migration-of-ovarian-carcinoma-cells-in-vitro-and-in-vivo
#13
Fangfang Lu, Hong Xu, Qi Wang, Meiyi Li, Jiahua Meng, Yan Kuang
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase, which targets histone H3 lysine 27. Studies have reported that EZH2 is involved in the development of several types of tumor, including ovarian cancer. p16, a well-known cell cycle regulator, has been demonstrated to be a tumor suppressor gene in a variety of malignant cells. However, the regulatory association between EZH2 and p16 in ovarian cancer remains to be fully elucidated. The present study aimed to determine whether EZH2 is involved in the development of ovarian cancer by regulating the expression of p16...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29435024/expression-of-ezh2-is-associated-with-poor-outcome-in-colorectal-cancer
#14
Zhuanpeng Chen, Ping Yang, Wanglin Li, Feng He, Jianchang Wei, Tong Zhang, Junbin Zhong, Huacui Chen, Jie Cao
Enhancer of zeste homolog 2 (EZH2), the critical component of polycomb group protein family, has been demonstrated to be overexpressed in various types of human cancer, including hepatocellular carcinoma, breast, bladder and lung cancer. The mechanism of how EZH2 promotes oncogenesis has also been well studied. However, little is known about the role of EZH2 in colorectal cancer (CRC). The main purpose of the present study was to analyze the association between EZH2 expression and the clinicopathological features of CRC...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434212/carm1-expressing-ovarian-cancer-depends-on-the-histone-methyltransferase-ezh2-activity
#15
Sergey Karakashev, Hengrui Zhu, Shuai Wu, Yuhki Yokoyama, Benjamin G Bitler, Pyoung-Hwa Park, Jeong-Heon Lee, Andrew V Kossenkov, Krutika Satish Gaonkar, Huihuang Yan, Ronny Drapkin, Jose R Conejo-Garcia, David W Speicher, Tamas Ordog, Rugang Zhang
CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in human cancers. However, clinically applicable cancer therapeutic strategies based on CARM1 expression remain to be explored. Here, we report that EZH2 inhibition is effective in CARM1-expressing epithelial ovarian cancer. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppresses the growth of CARM1-expressing, but not CARM1-deficient, ovarian tumors in two xenograft models and improves the survival of mice bearing CARM1-expressing ovarian tumors...
February 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29433384/region-specific-knock-out-reveals-distinct-roles-of-chromatin-modifiers-in-adult-neurogenic-niches
#16
Christopher T Rhodes, Giulia Zunino, Shu-Wei Angela Huang, Sandra M Cardona, Astrid E Cardona, Mitchel S Berger, Vance P Lemmon, Chin-Hsing Annie Lin
Histone methyltransferases (HMTs) are present in heterogeneous cell populations within the adult brain including neurogenic niches. Yet the question remains whether loss of HMTs and the resulting changes in histone methylation alter cell fate in a region-specific manner. We utilized stereotaxic injection of Cre recombinant protein into the adult neurogenic niches, the subventricular zone (SVZ) adjacent to the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus. We confirmed that Cre protein was enzymatically active in vivo and recombination events were restricted to the vicinity of injection areas...
February 13, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29432129/identification-of-two-distinct-classes-of-the-human-ino80-complex-genome-wide
#17
John S Runge, Jesse R Raab, Terry Magnuson
Chromatin remodeling and histone modifying enzymes play a critical role in shaping the regulatory output of a cell. Although much is known about these classes of proteins, identifying the mechanisms by which they coordinate gene expression programs remains an exciting topic of investigation. One factor that may contribute to the targeting and activity of chromatin regulators is local chromatin landscape. We leveraged genomic approaches and publically-available datasets to characterize the chromatin landscape at targets of the human INO80 chromatin remodeling complex (INO80-C)...
February 5, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29425303/regulation-of-the-positive-transcriptional-effect-of-plzf-through-a-non-canonical-ezh2-activity
#18
Myriam Koubi, Mathilde Poplineau, Julien Vernerey, Lia N'Guyen, Guillaume Tiberi, Sylvain Garciaz, Abdessamad El-Kaoutari, Muhammad A Maqbool, Jean-Christophe Andrau, Christel Guillouf, Andrew J Saurin, Estelle Duprez
The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level...
February 7, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29423052/mage-a11-is-activated-through-tfcp2-zeb1-binding-sites-de-methylation-as-well-as-histone-modification-and-facilitates-escc-tumor-growth
#19
Shina Liu, Fei Liu, Weina Huang, Lina Gu, Lingjiao Meng, Yingchao Ju, Yunyan Wu, Juan Li, Lihua Liu, Meixiang Sang
Recently, we have reported that the product of Melanoma Antigens Genes (MAGE) family member MAGE-A11 is an independent poor prognostic marker for esophageal squamous cell carcinoma (ESCC). However, the reason how MAGE-A11 is activated in ESCC progression still remains unclear. In the current study, we demonstrated that DNA methylation and the subsequent histone posttranslational modifications play crucial roles in the regulation of MAGE-A11 in ESCC progression. We found that the methylation rate of TFCP2/ZEB1 binding site on MAGE-A11 promoter in ESCC tissues and cells is higher than the normal esophageal epithelial tissues and cells...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29422082/cbx7-regulates-stem-cell-like-properties-of-gastric-cancer-cells-via-p16-and-akt-nf-%C3%AE%C2%BAb-mir-21-pathways
#20
Su-Jie Ni, Li-Qin Zhao, Xiao-Feng Wang, Zhen-Hua Wu, Rui-Xi Hua, Chun-Hua Wan, Jie-Yun Zhang, Xiao-Wei Zhang, Ming-Zhu Huang, Lu Gan, Hua-Lin Sun, Goberdhan P Dimri, Wei-Jian Guo
BACKGROUND: Chromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs' constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms...
February 8, 2018: Journal of Hematology & Oncology
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