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Cancer progression chromatin

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https://www.readbyqxmd.com/read/28526299/mir-200a-regulates-cdk4-6-inhibitor-effect-by-targeting-cdk6-in-metastatic-melanoma
#1
Matias A Bustos, Shigeshi Ono, Diego M Marzese, Takashi Oyama, Yuuki Iida, Garrett Cheung, Nellie Nelson, Sandy C Hsu, Qiang Yu, Dave S B Hoon
Cyclin-dependent kinase (CDK) 4 and 6 pathway is frequently dysregulated in cutaneous melanoma. Recently, CDK4/6 inhibitors have shown promising clinical activity against several cancer types, including melanoma. Here, we demonstrate that miR-200a decreases CDK6 expression and thus reduces the response of CDK4/6 inhibitor in highly proliferative metastatic melanoma. Down-regulation of miR-200a expression in melanoma cells is associated with disease progression and a higher number of lymph node metastases. Furthermore, miR-200a expression is epigenetically modulated by both DNA methylation at the promoter region and chromatin accessibility of an upstream genomic region with enhancer activity...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28524162/targeted-sequencing-based-analyses-of-candidate-gene-variants-in-ulcerative-colitis-associated-colorectal-neoplasia
#2
Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai, Kapaettu Satyamoorthy
BACKGROUND: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. METHODS: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28522598/immunotherapeutic-approaches-of-il-1-neutralization-in-the-tumor-microenvironment
#3
REVIEW
Ron N Apte, Elena Voronov
IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type I (IL-1R1) and induce similar biologic functions. The IL-1R antagonist (IL-1Ra) is a physiologic inhibitor of IL-1R1 signaling. In the tumor microenvironment, IL-1 is expressed by malignant, stromal, and infiltrating cells and supports tumor invasiveness and progression. We have shown that in the tumor microenvironment, the IL-1 agonistic molecules act different as a result of their local amounts and their compartmentalization within the producing cells...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28514453/chromatin-states-define-tumour-specific-t-cell-dysfunction-and-reprogramming
#4
Mary Philip, Lauren Fairchild, Liping Sun, Ellen L Horste, Steven Camara, Mojdeh Shakiba, Andrew C Scott, Agnes Viale, Peter Lauer, Taha Merghoub, Matthew D Hellmann, Jedd D Wolchok, Christina S Leslie, Andrea Schietinger
Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours to progress. The epigenetic regulation of T cell dysfunction and therapeutic reprogrammability (for example, to immune checkpoint blockade) is not well understood. Here we show that T cells in mouse tumours differentiate through two discrete chromatin states: a plastic dysfunctional state from which T cells can be rescued, and a fixed dysfunctional state in which the cells are resistant to reprogramming. We identified surface markers associated with each chromatin state that distinguished reprogrammable from non-reprogrammable PD1(hi) dysfunctional T cells within heterogeneous T cell populations from tumours in mice; these surface markers were also expressed on human PD1(hi) tumour-infiltrating CD8 T cells...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28504714/cytoplasmic-translocation-of-mta1-coregulator-promotes-de-repression-of-sgk1-transcription-in-hypoxic-cancer-cells
#5
H Marzook, S Deivendran, B George, G Reshmi, T R Santhoshkumar, R Kumar, M R Pillai
Chromatin remodeling factor metastatic tumor protein 1 (MTA1), one of the most upregulated oncogene in human cancer, has an important role in gene expression, cell survival and promoting hypoxic response. Successful cancer progression is dependent on the ability of cells to utilize its survival pathways for adapting to hypoxic microenvironment. Although MTA1 is a stress-responsive gene, but whether hypoxia modulates its function and its role in engaging other core stress-responsive survival pathway(s) remains unknown...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28504694/the-prohibitin-repressive-interaction-with-e2f1-is-rapidly-inhibited-by-androgen-signalling-in-prostate-cancer-cells
#6
S Koushyar, G Economides, S Zaat, W Jiang, C L Bevan, D A Dart
Prohibitin (PHB) is a tumour suppressor molecule with pleiotropic activities across several cellular compartments including mitochondria, cell membrane and the nucleus. PHB and the steroid-activated androgen receptor (AR) have an interplay where AR downregulates PHB, and PHB represses AR. Additionally, their cellular locations and chromatin interactions are in dynamic opposition. We investigated the mechanisms of cell cycle inhibition by PHB and how this is modulated by AR in prostate cancer. Using a prostate cancer cell line overexpressing PHB, we analysed the gene expression changes associated with PHB-mediated cell cycle arrest...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28504305/intranuclear-and-higher-order-chromatin-organization-of-the-major-histone-gene-cluster-in-breast-cancer
#7
Andrew J Fritz, Prachi N Ghule, Joseph R Boyd, Coralee E Tye, Natalie A Page, Deli Hong, Adam S Weinheimer, A Rasim Barutcu, Diana L Gerrard, Seth Frietze, Sayyed K Zaidi, Anthony Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Alterations in nuclear morphology are common in cancer progression. However, the degree to which gross morphological abnormalities translate into compromised higher-order chromatin organization is poorly understood. To explore the functional links between gene expression and chromatin structure in breast cancer, we performed RNA-seq gene expression analysis on the basal breast cancer progression model based on human MCF10A cells. Positional gene enrichment identified the major histone gene cluster at chromosome 6p22 as one of the most significantly upregulated (and not amplified) clusters of genes from the normal-like MCF10A to premalignant MCF10AT1 and metastatic MCF10CA1a cells...
May 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28496363/prognostic-value-of-histone-chaperone-fact-subunits-expression-in-breast-cancer
#8
Kristopher Attwood, Daria Fleyshman, Laura Prendergast, Geraldine Paszkiewicz, Angela R Omilian, Wiam Bshara, Katerina Gurova
Understanding the underlying reasons for tumor aggressiveness, such as why some tumors grow slowly and locally, while others rapidly progress to a lethal metastatic disease, is still limited. This is especially critical in breast cancer (BrCa) due to its high prevalence and also due to the possibility that it can be detected early. Several oncogenes and tumor suppressors have been identified and are used in the prognosis and treatment of BrCa. However, even with these markers, the outcome within BrCa subtypes is highly variable...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28493830/ing5-knockdown-enhances-migration-and-invasion-of-lung-cancer-cells-by-inducing-emt-via-egfr-pi3k-akt-and-il-6-stat3-signaling-pathways
#9
Xin-Li Liu, Xu-Tao Zhang, Jin Meng, Hong-Fei Zhang, Yong Zhao, Chen Li, Yang Sun, Qi-Bing Mei, Feng Zhang, Tao Zhang
ING5 belongs to the Inhibitor of Growth (ING) candidate tumor suppressor family, whose functions have been involved in the regulation of chromatin remodeling, cell cycle progression, proliferation and apoptosis. Our previous study has shown that ING5 overexpression inhibits lung cancer aggressiveness via suppressing epithelial to mesenchymal transition (EMT). However, the mechanisms remain largely unknown. In the current study, by Phospho-Kinase array and western blot, we have defined significantly upregulated EGFR/PI3K/Akt and IL-6/STAT3 oncogenic signaling pathways in ING5 knockdown A549 cells, which could be downregulated by ING5 overexpression...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28490482/conditional-ablation-of-raptor-in-the-male-germ-line-causes-infertility-due-to-meiotic-arrest-and-impaired-inactivation-of-sex-chromosomes
#10
Mengneng Xiong, Zhiping Zhu, Suwen Tian, Ruping Zhu, Shun Bai, Kaiqiang Fu, James G Davis, Zheng Sun, Joseph A Baur, Ke Zheng, Lan Ye
Rapamycin is a clinically important drug that is used in transplantation and cancer therapy but which causes a number of side effects, including male infertility. Its canonical target, mammalian target of rapamycin complex 1 (mTORC1), plays a key role in metabolism and binds chromatin; however, its precise role in the male germ line has not been elucidated. Here, we inactivate the core component, Raptor, to show that mTORC1 function is critical for male meiosis and the inactivation of sex chromosomes. Disruption of the Raptor gene impairs chromosomal synapsis and prevents the efficient spreading of silencing factors into the XY chromatin...
May 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28490335/ing5-suppresses-breast-cancer-progression-and-is-regulated-by-mir-24
#11
Shufang Cui, Xin Liao, Chao Ye, Xin Yin, Minghui Liu, Yeting Hong, Mengchao Yu, Yanqing Liu, Hongwei Liang, Chen-Yu Zhang, Xi Chen
BACKGROUND: The inhibitor of growth (ING) gene family of tumor suppressors is involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is a new member of the ING family whose function and regulation remain largely unknown. METHODS: Quantitative real-time PCR and western blot were used to examine the expression levels of ING5 in breast cancer tissues. The miRNAs that potentially targeted ING5 were determined by bioinformatics analysis and luciferase reporter assay...
May 10, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28487942/cyclic-amp-responsive-element-binding-protein-induces-metastatic-renal-cell-carcinoma-by-mediating-the-expression-of-matrix-metallopeptidase-2-9-and-proteins-associated-with-epithelial-mesenchymal-transition
#12
Xue Wang, Hui Cui, Zhongguan Lou, Shuaishuai Huang, Yu Ren, Ping Wang, Guobin Weng
Renal cell carcinoma (RCC) is the most frequently occurring malignancy of the kidney worldwide. Anti-angiogenic targeted therapies inhibit the progression of RCC, however, limited effects on the invasion or metastasis of tumor cells have been observed. Cyclic AMP responsive element‑binding protein (CREB) is a serine/threonine kinase that has been implicated in the regulation of cell proliferation, apoptosis, cycle progression and metastasis, amongst others. Our previous research demonstrated that phosphorylated CREB (pCREB) was upregulated in human renal cancer cell lines and tissues, and decreased pCREB at the Ser133 site inhibited the growth and metastatic activity of OS‑RC‑2 cells...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28485541/yy1-directly-suppresses-myct1-leading-to-laryngeal-tumorigenesis-and-progress
#13
Si-Yao Qu, Yuan-Yuan Sun, Yun-Hui Li, Zhen-Ming Xu, Wei-Neng Fu
YY1 is a key transcription factor and plays different roles in various cancers. However, role and mechanism of YY1 in laryngeal cancer are still unknown. YY1 and MYCT1 mRNA and protein levels were detected by Real-time RT-PCR and Western Blot methods, respectively. Binding of YY1 to MYCT1 promoter was predicted and confirmed by bioinformatics and chromatin immunoprecipitation assays, respectively. MYCT1 promoter activity was assessed by dual luciferase assay system. Laryngeal cancer cell proliferation, migration, and apoptosis were evaluated by cell viability, colony formation, cell scratch assay, transwell assay, and flow cytometry methods, respectively...
May 9, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28473532/novel-androgen-receptor-co-regulator-grhl2-exerts-both-oncogenic-and-anti-metastatic-functions-in-prostate-cancer
#14
Steve Paltoglou, Rajdeep Das, Scott L Townley, Theresa Hickey, Gerard Tarulli, Isabel Coutinho, Rayzel C Fernandes, Adrienne Hanson, Iza Denis, Jason Carroll, Scott M Dehm, Ganesh V Raj, Steve Plymate, Wayne D Tilley, Luke A Selth
Alterations to the expression and activity of androgen receptor (AR) co-regulators in prostate cancer is an important mechanism driving disease progression and therapy resistance. Using a novel proteomic technique, we identified a new AR co-regulator, the transcription factor Grainyhead-like 2 (GRHL2), and demonstrated its essential role in the oncogenic AR signaling axis. GRHL2 colocalized with AR in prostate tumors and was frequently amplified and upregulated in prostate cancer. Importantly, GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and co-located with AR at specific sites on chromatin to regulate genes relevant to disease progression...
May 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28465488/rack1-promotes-lung-cancer-cell-growth-via-an-mcm7-rack1-akt-signaling-complex
#15
Liangru Fei, Yinan Ma, Meiyu Zhang, Xiaofang Liu, Yuan Luo, Congcong Wang, Haiyan Zhang, Wenzhu Zhang, Yuchen Han
MCM7, a member of the miniature chromosome maintenance (MCM) protein family, is crucial for the initiation of DNA replication and proliferation in eukaryotic cells. In this report, we demonstrate that RACK1 regulates cell growth and cell cycle progression in human non-small-cell lung cancer by mediating MCM7 phosphorylation through an MCM7/RACK1/Akt signaling complex. RACK1 functions as a central scaffold that brings Akt into physical proximity with MCM7. Overexpression of RACK1 increases interactions between Akt and MCM7 and promotes Akt-dependent MCM7 phosphorylation, which in turn increases MCM7 binding to chromatin and MCM complex formation...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465257/5-fluorouracil-targets-histone-acetyltransferases-p300-cbp-in-the-treatment-of-colorectal-cancer
#16
Changzheng Du, Dandan Huang, Yifan Peng, Yunfeng Yao, Ying Zhao, Yang Yang, Haiying Wang, Linlin Cao, Wei-Guo Zhu, Jin Gu
Although 5-fluorouracil (5-FU) is known to interfere with the synthesis of ribonucleic acid and deoxyribonucleic acid, the mechanism underlying its therapeutic efficacy in colorectal cancer (CRC) has not been fully elucidated. We aimed to investigate the influence of 5-FU on histone acetylation, a well-established anti-cancer target, to reveal novel pharmacological effects of 5-FU and their significance for CRC therapy. Results demonstrated that 5-FU induces global histone de-acetylation in multiple CRC cell lines...
April 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28454092/hoxb7-promotes-tumor-progression-via-bfgf-induced-activation-of-mapk-erk-pathway-and-indicated-poor-prognosis-in-hepatocellular-carcinoma
#17
Wei-Min Wang, Yang Xu, Yao-Hui Wang, Hai-Xiang Sun, Yun-Fan Sun, Yi-Feng He, Qing-Feng Zhu, Bo Hu, Xin Zhang, Jing-Lin Xia, Shuang-Jian Qiu, Jian Zhou, Xin-Rong Yang, Jia Fan
The homeobox-containing gene HOXB7 plays an important role in the pathogenesis and progression of many cancers, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study comprehensively analyzed the expression and clinical significance of HOXB7 in HCC and explored its potential mechanism in tumor progression. We found HOXB7 was highly expressed in HCC cell lines with highly metastatic potential and cancerous tissues from patients with tumor recurrence. The abilities of proliferation, migration, and invasion were notably decreased by depletion of HOXB7, and were enhanced by its enforced expression in vitro...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450738/dna-methylation-an-epigenetic-mark-of-cellular-memory
#18
REVIEW
Mirang Kim, Joseph Costello
DNA methylation is a stable epigenetic mark that can be inherited through multiple cell divisions. During development and cell differentiation, DNA methylation is dynamic, but some DNA methylation patterns may be retained as a form of epigenetic memory. DNA methylation profiles can be useful for the lineage classification and quality control of stem cells such as embryonic stem cells, induced pluripotent cells and mesenchymal stem cells. During cancer initiation and progression, genome-wide and gene-specific DNA methylation changes occur as a consequence of mutated or deregulated chromatin regulators...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#19
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28441948/over-expressed-long-noncoding-rna-hoxa11-as-promotes-cell-cycle-progression-and-metastasis-in-gastric-cancer
#20
Zhili Liu, Zhenyao Chen, Ruihua Fan, Bin Jiang, Xin Chen, Qinnan Chen, Fengqi Nie, Kaihua Lu, Ming Sun
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1...
April 26, 2017: Molecular Cancer
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