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S F Lax
The 2014 World Health Organization (WHO) classification of uterine tumors revealed simplification of the classification by fusion of several entities and the introduction of novel entities. Among the multitude of alterations, the following are named: a simplified classification for precursor lesions of endometrial carcinoma now distinguishes between hyperplasia without atypia and atypical hyperplasia, the latter also known as endometrioid intraepithelial neoplasia (EIN). For endometrial carcinoma a differentiation is made between type 1 (endometrioid carcinoma with variants and mucinous carcinoma) and type 2 (serous and clear cell carcinoma)...
October 13, 2016: Der Pathologe
Na Keum Lee, Jung Hwa Lee, Won Kyu Kim, Seongju Yun, Young Hoon Youn, Chan Hyuk Park, Yun Young Choi, Hogeun Kim, Sang Kil Lee
HOTAIR, a long non-coding RNA (lncRNA), plays a crucial role in tumor initiation and metastasis by interacting with the PRC2 complex and the modulation of its target genes. The role of HOTAIR in gastrointestinal stromal tumors (GISTs) is remains unclear. Herein we investigate the mechanism of HOTAIR in the genesis and promotion of GISTs. The expression of HOTAIR was found to be higher in surgically resected high-risk GISTs than that in low- and intermediate-risk GISTs. Using GIST-T1 and GIST882 cells, we demonstrated that HOTAIR repressed apoptosis, was associated with cell cycle progression, and controlled the invasion and migration of GIST cells...
September 21, 2016: Oncotarget
Giorgio Oliviero, Gerard L Brien, Ariane Watson, Gundula Streubel, Emilia Jerman, Darrell Andrews, Benjamin Doyle, Nayla Munawar, Kieran Wynne, John Crean, Adrian P Bracken, Gerard Cagney
Polycomb proteins assemble to form complexes with important roles in epigenetic regulation. The Polycomb Repressive Complex 2 (PRC2) modulates the di- and tri-methylation of lysine 27 on histone H3, each of which are associated with gene repression. Although three subunits, EZH1/2, SUZ12 and EED, form the catalytic core of PRC2, a wider group of proteins associate with low stoichiometry. This raises the question of whether dynamic variation of the PRC2 interactome results in alternative forms of the complex during differentiation...
September 15, 2016: Molecular & Cellular Proteomics: MCP
Danfeng Sun, Yanwei Lin, Jie Hong, Haoyan Chen, Nisha Nagarsheth, Dongjun Peng, Shuang Wei, Emina Huang, Jingyuan Fang, Ilona Kryczek, Weiping Zou
Th22 cells traffic to and retain in the colon cancer microenvironment, and target core stem cell genes and promote colon cancer stemness via STAT3 and H3K79me2 signaling pathway and contribute to colon carcinogenesis. However, whether Th22 cells affect colon cancer cell proliferation and apoptosis remains unknown. We studied the interaction between Th22 cells and colon cancer cells in the colon cancer microenvironment. Colon cancer proliferation was examined by flow cytometry analysis and H(3) thymidine incorporation...
August 2016: Oncoimmunology
Nan Xie, Cheng Wang, Zehang Zhuang, Jinson Hou, Xiqiang Liu, Yue Wu, Haichao Liu, Hongzhang Huang
We aimed to determine the specific miRNA profile of tumor budding cells and investigate the potential role of miR-320a in invasion and metastasis of tongue squamous cell carcinoma (TSCC). We collected tumor budding cells and paired central tumor samples from five TSCC specimens with laser capture microdissection and examined the specimens using a miRNA microarray. The specific miRNA signature of tumor budding cells was identified. We found that miR-320a was dramatically decreased in tumor budding cells. Knockdown of miR-320a significantly enhanced migration and invasion of TSCC cell lines...
August 25, 2016: Oncotarget
Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon
BACKGROUND: A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs)...
September 2016: Journal of Pathology and Translational Medicine
Hong-Wei Ma, Min Xie, Ming Sun, Tian-Yu Chen, Rong-Rong Jin, Tian-Shi Ma, Qin-Nan Chen, Er-Bao Zhang, Xue-Zhi He, Wei De, Zhi-Hong Zhang
Gastric cancer (GC) is the third leading cause of cancer death due to its poor prognosis and limited treatment options. Evidence indicates that pseudogene-derived long noncoding RNAs (lncRNAs) may be important players in human cancer progression, including GC. In this paper, we report that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in GC. Additionally, a higher level of DUXAP8 expression in GC was significantly associated with greater tumor size, advanced clinical stage, and lymphatic metastasis...
August 5, 2016: Oncotarget
Jasmine Naru, Ritu Aggarwal, Usha Singh, Ashok Kumar Mohanty, Deepak Bansal, Navdeep Mangat, Nandita Kakkar, Navneet Agnihotri
There is close proximity of vitreous humor with the tumor bulk in eyes with retinoblastoma. This renders vitreous humor a promising source to evaluate disease-specific protein targets in retinoblastoma. We studied the differential proteome of vitreous fluid in retinoblastoma tumors (n = 4) as compared to controls (n = 4). The vitreous humor was depleted off the high abundant fraction using MARS-6 affinity column. Subsequently, the tryptic peptides were derivatised with iTRAQ labels. The labelled peptides were pooled and subjected to fractionation using bRPLC...
August 3, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yiqun Zhang, Ji-Fan Hu, Hong Wang, Jiuwei Cui, Sujun Gao, Andrew R Hoffman, Wei Li
The normally imprinted insulin-like growth factor II (IGF2) gene is aberrantly upregulated in a variety of human malignancies, yet the mechanisms underlying this dysregulation are still poorly defined. In this report, we used a novel CRISPR Cas9-guided chromatin immunoprecipitation assay to characterize the molecular components that participate in the control of IGF2 gene expression in human tumor cells. We found that miR483, an oncogenic intronic miRNA, binds to the most upstream imprinted IGF2 promoter, P2...
July 29, 2016: Oncotarget
Maria Ramaglia, Velia D'Angelo, Adriana Iannotta, Daniela Di Pinto, Elvira Pota, Maria Carmen Affinita, Vittoria Donofrio, Maria Elena Errico, Angela Lombardi, Cristiana Indolfi, Fiorina Casale, Michele Caraglia
BACKGROUND: Enhancer of Zeste Drosophila Homologue 2 (EZH2) is a key regulator of transcription as a member of polycomb repressive complex 2 (PRC2) which exerts repression of downstream genes and is correlated to invasiveness and progression of different tumours. Therefore, we evaluated the expression of PRC2 proteins in pediatric soft tissue sarcoma (rhabdomyosarcoma, RMS and extraosseous Ewing sarcoma, EES) correlating them to the clinical outcome of the patients. METHODS: We analyzed PRC2 protein expression by quantitative real time PCR, western blotting and immunohistochemistry in 17 soft tissue sarcomas (11 RMS and 6 EES) enrolled at Paediatric Oncology Units of the Second University of Naples...
2016: Cancer Cell International
Garima Kushwaha, Mikhail Dozmorov, Jonathan D Wren, Jing Qiu, Huidong Shi, Dong Xu
BACKGROUND: Methylation changes are frequent in cancers, but understanding how hyper- and hypomethylated region changes coordinate, associate with genomic features, and affect gene expression is needed to better understand their biological significance. The functional significance of hypermethylation is well studied, but that of hypomethylation remains limited. Here, with paired expression and methylation samples gathered from a patient/control cohort, we attempt to better characterize the gene expression and methylation changes that take place in cancer from B cell chronic lymphocyte leukemia (B-CLL) samples...
2016: Human Genomics
Vladimir A Botchkarev, Andrei N Mardaryev
The Polycomb group proteins are transcriptional repressors that are critically important in the control of stem cell activity and maintenance of the identity of differentiated cells. Polycomb proteins interact with each other to form chromatin-associated repressive complexes (Polycomb repressive complexes 1 and 2) leading to chromatin compaction and gene silencing. However, the roles of the distinct components of the Polycomb repressive complex 2 in the control of skin development and keratinocyte differentiation remain obscure...
August 2016: Journal of Investigative Dermatology
Jiahui An, Mengying Wu, Xiaoru Xin, Zhuojia Lin, Xiaonan Li, Qidi Zheng, Xin Gui, Tianming Li, Hu Pu, Haiyan Li, Dongdong Lu
Cancer stem cells are associated with tumor recurrence. IKK is a protein kinase that is composed of IKKα, IKKβ, IKKγ. Herein, we demonstrate that IKKα plus IKKβ promoted and IKKγ inhibited liver cancer stem cell growth in vitro and in vivo. Mechanistically, IKKα plus IKKβ enhanced and IKKγ inhibited the interplay among HP1α, HP1β and HP1γ that competes for the interaction among HP1α, SUZ12, HEZ2. Therefore, IKKα plus IKKβ inhibited and IKKγ enhanced the activity of H3K27 methyltransferase SUZ12 and EZH2, which methylates H3K27 immediately sites on HOTAIR promoter region...
June 29, 2016: Oncotarget
Hao Zhang, Zheng Xing, Saravana Kumar Kailasam Mani, Brigitte Bancel, David Durantel, Fabien Zoulim, Elizabeth J Tran, Philippe Merle, Ourania Andrisani
UNLABELLED: Chronic hepatitis B virus (HBV) infection is a major factor in hepatocellular carcinoma (HCC) pathogenesis by a mechanism not yet understood. Elucidating mechanisms of HBV-mediated hepatocarcinogenesis is needed to gain insights into classification and treatment of HCC. In HBV replicating cells, including virus-associated HCCs, suppressor of zeste 12 homolog (SUZ12), a core subunit of Polycomb repressive complex2 (PRC2), undergoes proteasomal degradation. This process requires the long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR)...
October 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Lamia Abdalkader, Takashi Oka, Katsuyoshi Takata, Hiaki Sato, Ichiro Murakami, Arie P Otte, Tadashi Yoshino
The Polycomb repressive complex-2 members (EZH2, EED, SUZ12 and EZH1) are important regulators of haematopoiesis, cell cycle and differentiation. Over-expression of EZH2 has been linked to cancer metastases and poor prognosis. Detailed information on the expression of other members in normal and neoplastic lymphoid tissue remains to be elucidated. Immunohistochemical and immunofluorescent analyses of 156 samples from haematopoietic neoplasms patients and 27 haematopoietic cell lines were used. B-cell neoplasms showed a significant over-expression of EZH2, EED and SUZ12 in the aggressive subtypes compared to the indolent subtypes and normal tissue (p = 0...
August 2016: Pathology
Mohamad Zamani-Ahmadmahmudi
Canine breast cancer was considered as an ideal model of comparative oncology for the human breast cancer, as there is significant overlap between biological and clinical characteristics of the human and canine breast cancer. We attempt to clarify expression profile of the embryonic stem cell (ES) gene signatures in canine breast cancer. Using microarray datasets (GSE22516 and GSE20718), expression of the three major ES gene signatures (modules or gene-sets), including Myc, ESC-like, and PRC modules, was primarily analyzed through Gene-Set Enrichment Analysis (GSEA) method in tumor and healthy datasets...
August 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Sylvia Mahara, Puay Leng Lee, Min Feng, Vinay Tergaonkar, Wee Joo Chng, Qiang Yu
Despite the established oncogenic function of Polycomb repressive complex 2 (PRC2) in human cancers, its role as a tumor suppressor is also evident; however, the mechanism underlying the regulation of the paradoxical functions of PRC2 in tumorigenesis is poorly understood. Here we show that hypoxia-inducible factor 1, α-subunit (HIFI-α) is a crucial modulator of PRC2 and enhancer of zeste 2 (EZH2) function in breast cancer. Interrogating the genomic expression of breast cancer indicates high HIF1A activity correlated with high EZH2 expression but low PRC2 activity in triple-negative breast cancer compared with other cancer subtypes...
June 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
Veit Schwämmle, Simone Sidoli, Chrystian Ruminowicz, Xudong Wu, Chung-Fan Lee, Kristian Helin, Ole N Jensen
Histones are abundant chromatin constituents carrying numerous post-translational modifications (PTMs). Such PTMs mediate a variety of biological functions, including recruitment of enzymatic readers, writers and erasers that modulate DNA replication, transcription and repair. Individual histone molecules contain multiple coexisting PTMs, some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. Here, we present an integrated experimental and computational systems level molecular characterization of histone PTMs and PTM crosstalk...
August 2016: Molecular & Cellular Proteomics: MCP
Prasanna K Kallingappa, Pavla M Turner, Michael P Eichenlaub, Andria L Green, Fleur C Oback, Alice M Chibnall, David N Wells, Björn Oback
Reprogramming by nuclear transfer (NT) cloning forces cells to lose their lineage-specific epigenetic marks and reacquire totipotency. This process often produces molecular anomalies that compromise clone development. We hypothesized that quiescence alters the epigenetic status of somatic NT donor cells and elevates their reprogrammability. To test this idea, we compared chromatin composition and cloning efficiency of serum-starved quiescent (G0) fibroblasts versus nonstarved mitotically selected (G1) controls...
July 2016: Biology of Reproduction
Simin Zhang, Guangzheng Zhong, Wang He, Hao Yu, Jian Huang, Tianxin Lin
PURPOSE: While lncRNAs (long noncoding RNAs) have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle invasive bladder cancer remain largely unknown. We identified a lncRNA termed lncRNA-UNMIBC (up-regulated in nonmuscle invasive bladder cancer) and evaluated its prognostic value in patients with primary nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We analyzed the expression of lncRNA-UNMIBC in the tissues of 75 cases of primary nonmuscle invasive bladder cancer and adjacent normal mucosa by quantitative real-time polymerase chain reaction...
October 2016: Journal of Urology
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