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Cancer progression chromatin

Siu Ling Wong, Denisa D Wagner
Peptidylarginine deiminase 4 (PAD4) is a nuclear citrullinating enzyme that is critically involved in the release of decondensed chromatin from neutrophils as neutrophil extracellular traps (NETs). NETs, together with fibrin, are implicated in host defense against pathogens; however, the formation of NETs (NETosis) has injurious effects that may outweigh their protective role. For example, PAD4 activity produces citrullinated neoantigens that promote autoimmune diseases, such as rheumatoid arthritis, to which PAD4 is genetically linked and where NETosis is prominent...
June 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Oriol Bachs, Edurne Gallastegui, Serena Orlando, Anna Bigas, José Manuel Morante-Redolat, Joan Serratosa, Isabel Fariñas, Rosa Aligué, Maria Jesús Pujol
The protein p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase (Cdk) inhibitors. It interacts with both the catalytic and the regulatory subunit (cyclin) and introduces a region into the catalytic cleave of the Cdk inducing its inactivation. Its inhibitory capacity can be modulated by specific tyrosine phosphorylations. p27Kip1 also behaves as a transcriptional regulator. It associates with specific chromatin domains through different transcription factors. ChIP on chip, ChIP-seq and expression microarray analysis allowed the identification of the transcriptional programs regulated by p27Kip1 ...
May 25, 2018: Oncotarget
Xiaoru Xin, Mengying Wu, Qiuyu Meng, Chen Wang, Yanan Lu, Yuxin Yang, Xiaonan Li, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Jiao Li, Song Jia, Dongdong Lu
BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. RESULTS: HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer...
June 12, 2018: Molecular Cancer
Sarah M Greenblatt, Na Man, Pierre-Jacques Hamard, Takashi Asai, Daniel Karl, Concepcion Martinez, Daniel Bilbao, Vasileios Stathais, Anna McGrew-Jermacowicz, Stephanie Duffort, Madhavi Tadi, Ezra Blumenthal, Samantha Newman, Ly Vu, Ye Xu, Fan Liu, Stephan C Schurer, Michael T McCabe, Ryan G Kruger, Mingjiang Xu, Feng-Chun Yang, Daniel Tenen, Justin Watts, Francisco Vega, Stephen D Nimer
Chromatin-modifying enzymes, and specifically the protein arginine methyltransferases (PRMTs), have emerged as important targets in cancer. Here, we investigated the role of CARM1 in normal and malignant hematopoiesis. Using conditional knockout mice, we show that loss of CARM1 has little effect on normal hematopoiesis. Strikingly, knockout of Carm1 abrogates both the initiation and maintenance of acute myeloid leukemia (AML) driven by oncogenic transcription factors. We show that CARM1 knockdown impairs cell-cycle progression, promotes myeloid differentiation, and ultimately induces apoptosis...
June 11, 2018: Cancer Cell
Emi Sato, Kentaro Nakayama, Sultana Razia, Kohei Nakamura, Masako Ishikawa, Toshiko Minamoto, Tomoka Ishibashi, Hitomi Yamashita, Kouji Iida, Satoru Kyo
AT-rich interactive domain 1A (ARID1A) and AT-rich interactive domain 1B (ARID1B) are subunits of the SWI/SNF chromatin complex. ARID1A is a tumor suppressor gene that is frequently mutated (46%) in ovarian clear cell carcinomas (OCCC). Loss of ARID1B in an ARID1A-deficient background eliminates the intact SWI/SNF complex, indicating that ARID1B is essential for the formation or stabilization of an intact SWI/SNF complex and, thus, the survival of ARID1A-mutant cancer cell lines. In this study, we investigated the clinicopathologic and prognostic relevance of ARID1B in OCCC by immunohistochemical analysis of 53 OCCC patient samples and loss-of-function experiments in OCCC cell lines...
June 8, 2018: International Journal of Molecular Sciences
Santiago Haase, María Belén Garcia-Fabiani, Stephen Carney, David Altshuler, Felipe J Núñez, Flor M Méndez, Fernando Núñez, Pedro R Lowenstein, Maria G Castro
ATRX is a chromatin remodeling protein whose main function is the deposition of the histone variant H3.3. ATRX mutations are widely distributed in glioma, and correlate with alternative lengthening of telomeres (ALT) development, but they also affect other cellular functions related to epigenetic regulation. Areas covered: We discuss the main molecular characteristics of ATRX, from its various functions in normal development to the effects of its loss in ATRX syndrome patients and animal models. We focus on the salient consequences of ATRX mutations in cancer, from a clinical to a molecular point of view, focusing on both adult and pediatric glioma...
June 11, 2018: Expert Opinion on Therapeutic Targets
Katia Ruggero, Sonia Farran-Matas, Adrian Martinez-Tebar, Alvaro Aytes
Purpose of Review: An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Recent Findings: Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency...
2018: Current Molecular Biology Reports
Peisheng Chen, Zilong Yao, Ganming Deng, Yilong Hou, Siwei Chen, Yanjun Hu, Bin Yu
Osteomyelitis (OM) is a complicated and serious disease and its underlying molecular signatures of disease initiation and progression remain unclear. Staphylococcus aureus (S. aureus) is the most common causative agent of OM. Previous study of Banchereau et al. has established a link between whole blood transcription profiles and clinical manifestations in patients infected with S. aureus . However, the differentially expressed genes (DEGs) in OM induced by S. aureus infection have not been intensively investigated...
2018: Frontiers in Microbiology
Julita Pietrzak, Corinne M Spickett, Tomasz Płoszaj, László Virág, Agnieszka Robaszkiewicz
Although electrophiles are considered as detrimental to cells, accumulating recent evidence indicates that proliferating non-cancerous and particularly cancerous cells utilize these agents for pro-survival and cell cycle promoting signaling. Hence, the redox shift to mild oxidant release must be balanced by multiple defense mechanisms. Our latest findings demonstrate that cell cycle progression, which dictates oxidant level in stress-free conditions, determines PARP1 transcription. Growth modulating factors regulate CDK4/6-RBs-E2Fs axis...
June 2, 2018: Redox Biology
Yang Hu, Qiong-Ni Zhu, Jun-Li Deng, Zhi-Xing Li, Guo Wang, Yuan-Shan Zhu
Cisplatin (CDDP) is one of the most commonly used chemotherapy drugs for the treatment of various cancers. Although platinum-based therapies are highly efficacious against rapidly proliferating malignant tumors, the development of CDDP resistance results in significant relapse as well as decreased overall survival rates, which is a significant obstacle in CDDP-based cancer therapy. Long non-coding RNAs (lncRNAs) are involved in cancer development and progression by the regulation of processes related to chromatin remodeling, transcription, and posttranscriptional processing...
2018: OncoTargets and Therapy
Angela Nebbioso, Francesco Paolo Tambaro, Carmela Dell'Aversana, Lucia Altucci
Defects in chromatin modifiers and remodelers have been described both for hematological and solid malignancies, corroborating and strengthening the role of epigenetic aberrations in the etiology of cancer. Furthermore, epigenetic marks-DNA methylation, histone modifications, chromatin remodeling, and microRNA-can be considered potential markers of cancer development and progression. Here, we review whether altered epigenetic landscapes are merely a consequence of chromatin modifier/remodeler aberrations or a hallmark of cancer etiology...
June 2018: PLoS Genetics
Jan-Henrik Mikesch, Wolfgang Hartmann, Linus Angenendt, Otmar Huber, Christoph Schliemann, Maria Francisca Arteaga, Eva Wardelmann, Claudia Rudack, Wolfgang E Berdel, Markus Stenner, Inga Grünewald
PURPOSE: Salivary gland cancer (SGC) is a rare and heterogeneous disease with significant differences in recurrence and metastasis characteristics. As yet, little is known about the mechanisms underlying the initiation and/or progression of these diverse tumors. In recent years, the AAA+ ATPase family members Pontin (RuvBL1, Tip49a) and Reptin (RuvBL2, Tip49b) have been implicated in various processes, including transcription regulation, chromatin remodeling and DNA damage repair, that are frequently deregulated in cancer...
June 5, 2018: Cellular Oncology (Dordrecht)
Danielle J Sanchez, David J Steger, Nicolas Skuli, Ankita Bansal, M Celeste Simon
OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a subtype of kidney cancer defined by robust lipid accumulation, which prior studies have indicated plays an important role in tumor progression. We hypothesized that the peroxisome proliferator-activated receptor gamma (PPARγ), detected in both ccRCC tumors and cell lines, promotes lipid storage in ccRCC and contributes to tumorigenesis in this setting. PPARγ transcriptionally regulates a number of genes involved in lipid and glucose metabolism in adipocytes, yet its role in ccRCC has not been described...
May 21, 2018: Molecular Metabolism
Ewa Forma, Paweł Jóźwiak, Piotr Ciesielski, Agnieszka Zaczek, Katarzyna Starska, Magdalena Bryś, Anna Krześlak
Enhancer of zest homolog 2 (EZH2) is a histone methyltransferase which plays a crucial role in cancer progression by regulation of genes involved in cellular processes such as proliferation, invasion and self-renewal. Activity and biological function of EZH2 are regulated by posttranslational modifications. It is suggested that EZH2 stability may be regulated by O-GlcNAc transferase (OGT), which is an enzyme catalyzing the addition of GlcNAc moieties to target proteins. In this study, we determined the impact of OGT on expression of EZH2 target genes FOXA1 and FOXC1, that are involved in breast cancer progression...
2018: PloS One
Ruiqiong Liu, Jie Gao, Yang Yang, Rongfang Qiu, Yu Zheng, Wei Huang, Yi Zeng, Yongqiang Hou, Shuang Wang, Shuai Leng, Dandan Feng, Wenqian Yu, Gancheng Sun, Hang Shi, Xu Teng, Yan Wang
Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. PHF1 [plant homeodomain (PHD) finger protein 1], which contains two kinds of histone reader modules, a Tudor domain and two PHD fingers, is an essential factor for epigenetic regulation and genome maintenance. While significant progress has been made in characterizing the function of the Tudor domain, the roles of the two PHD fingers are poorly defined...
May 29, 2018: Nucleic Acids Research
Hem Sapkota, Emilia Wasiak, John R Daum, Gary J Gorbsky
Cells delayed in metaphase with intact mitotic spindles undergo cohesion fatigue, where sister chromatids separate asynchronously, while cells remain in mitosis. Cohesion fatigue requires release of sister chromatid cohesion. However, the pathways that breach sister chromatid cohesion during cohesion fatigue remain unknown. Using moderate-salt buffers to remove loosely bound chromatin Cohesin, we show that "cohesive" Cohesin is not released during chromatid separation during cohesion fatigue. Using a regulated protein heterodimerization system to lock different Cohesin ring interfaces at specific times in mitosis, we show that the Wapl-mediated pathway of Cohesin release is not required for cohesion fatigue...
May 30, 2018: Molecular Biology of the Cell
Huazhang Wu, Xiufang Liu, Pihai Gong, Wei Song, Menghan Zhou, Yiping Li, Zhujiang Zhao, Hong Fan
Cancer cell invasion and metastasis are the leading causes of the high mortality rates in patients with malignant tumors. There is accumulating evidence to indicate that dysregulated long non‑coding RNAs (lncRNAs) may be involved in the progression of tumor invasion and metastasis. However, the regulatory mechanisms of the aberrant expression of lncRNAs remain largely unknown, although the roles of lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types in recent years...
May 25, 2018: Oncology Reports
Zhong Chen, Dayong Wu, Jennifer M Thomas-Ahner, Changxue Lu, Pei Zhao, Qingfu Zhang, Connor Geraghty, Pearlly S Yan, William Hankey, Benjamin Sunkel, Xiaolong Cheng, Emmanuel S Antonarakis, Qi-En Wang, Zhihua Liu, Tim H-M Huang, Victor X Jin, Steven K Clinton, Jun Luo, Jiaoti Huang, Qianben Wang
The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting therapies, how AR-V7 mediates genomic functions in CRPC remains largely unknown. Using a ChIP-exo approach, we show AR-V7 binds to distinct genomic regions and recognizes a full-length androgen-responsive element in CRPC cells and patient tissues. Remarkably, we find dramatic differences in AR-V7 cistromes across diverse CRPC cells and patient tissues, regulating different target gene sets involved in CRPC progression...
May 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
Johanna Melo-Cardenas, Yuanming Xu, Juncheng Wei, Can Tan, Sinyi Kong, Beixue Gao, Elena Montauti, Gina Kirsammer, Jonathan D Licht, Jindan Yu, Peng Ji, John D Crispino, Deyu Fang
Ras mutations are commonly observed in Juvenile Myelomonocytic Leukemia (JMML) and Chronic Myelomonocytic Leukemia (CMML). JMML and CMML transform into Acute Myeloid Leukemia (AML) in about 10% and 50% of patients respectively. However, how additional events cooperate with Ras to promote this transformation are largely unknown. We show that absence of the Ubiquitin-Specific-peptidase 22 (USP22), a component of the SAGA chromatin-remodeling complex linked to cancer progression, unexpectedly promotes AML transformation in mice expressing oncogenic KrasG12D/+ USP22 deficiency in KrasG12D/+ mice resulted in shorter survival compared to control mice...
May 29, 2018: Blood
B Madhu Krishna, Sanjib Chaudhary, Dipti Ranjan Mishra, Sanoj K Naik, S Suklabaidya, A K Adhya, Sandip K Mishra
BACKGROUND: Breast cancer (BC) is highly heterogeneous with ~ 60-70% of estrogen receptor positive BC patient's response to anti-hormone therapy. Estrogen receptors (ERs) play an important role in breast cancer progression and treatment. Estrogen related receptors (ERRs) are a group of nuclear receptors which belong to orphan nuclear receptors, which have sequence homology with ERs and share target genes. Here, we investigated the possible role and clinicopathological importance of ERRβ in breast cancer...
May 30, 2018: BMC Cancer
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