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https://www.readbyqxmd.com/read/28098896/microrna-194-represses-glioma-cell-epithelial%C3%A2-to%C3%A2-mesenchymal-transition-by-targeting-bmi1
#1
Xi Zhang, Chunyan Wei, Jin Li, Jiali Liu, Jianqiang Qu
MicroRNA-194 (miR-194) is frequently dysregulated in many types of cancer. However, the function of miR-194 in glioma remains unknown. In the present study, we aimed to investigate the biological functions of miR-194 in glioma and the potential molecular mechanism of miR-194 involved in glioma progression. We found that miR-194 expression was significantly reduced in glioma specimens and cell lines, as detected by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. The overexpression of miR-194 inhibited while the suppression of miR-194 promoted cell migration, invasion and epithelial mesenchymal transition (EMT) in glioma cells...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28079973/a-regulatory-bmi1-let-7i-erk3-pathway-controls-the-motility-of-head-and-neck-cancer-cells
#2
Lobna Elkhadragy, Minyi Chen, Kennon Miller, Muh-Hwa Yang, Weiwen Long
Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK), whose biological activity is tightly regulated by its cellular abundance. Recent studies have revealed that ERK3 is upregulated in multiple cancers and promotes cancer cell migration/invasion and drug resistance. Little is known, however, about how ERK3 expression level is upregulated in cancers. Here, we have identified the oncogenic polycomb group protein BMI1 as a positive regulator of ERK3 level in head and neck cancer cells...
November 9, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28041973/prognostic-significance-of-stromal-grem1-expression-in-colorectal-cancer
#3
Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Hyeon Jeong Oh, Xianyu Wen, Seorin Jeong, Nam Yun Cho, Woo Ho Kim, Gyeong Hoon Kang
Cancer associated fibroblasts (CAFs) are the dominant cell population in the cancer stroma. Gremlin 1 (GREM1), an antagonist of the bone morphogenetic protein pathway, is expressed by CAFs in a variety of human cancers. However, its biological significance for cancer patients is largely unknown. We applied RNA in situ hybridization (ISH) to evaluate the prognostic value of stromal GREM1 expression in a large cohort of 670 colorectal cancers (CRCs). Overall GREM1 expression in CRCs was lower than that of the matched normal mucosa, and GREM1 expression had a strong positive correlation with BMI1 and inverse correlations with EPHB2 and OLFM4...
December 29, 2016: Human Pathology
https://www.readbyqxmd.com/read/28004815/bmi1-positive-cells-in-the-lingual-epithelium-could-serve-as-cancer-stem-cells-in-tongue-cancer
#4
Toshihiro Tanaka, Naho Atsumi, Naohiro Nakamura, Hirotsugu Yanai, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Kazuichi Okazaki, Hiroo Ueno
We recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells (LESCs), which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. However, the precise role of LESCs in generating tongue tumors and Bmi1-positive cell lineage dynamics in tongue cancers are unclear. Here, using a mouse model of chemically (4-nitroquinoline-1-oxide: 4-NQO) induced tongue cancer and the multicolor lineage tracing method, we found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27965321/suppressing-p16ink4a-and-p14arf-pathways-overcomes-apoptosis-in-individualized-human-embryonic-stem-cells
#5
Wenqian Wang, Yanling Zhu, Ke Huang, Yongli Shan, Juan Du, Xiaoya Dong, Ping Ma, Penafei Wu, Jian Zhang, Wenhao Huang, Tian Zhang, Baojian Liao, Deyang Yao, Guangjin Pan, Jiajun Liu
Dissociation-induced apoptosis is a striking phenomenon in human embryonic stem cells (hESCs), but not in naïve mouse ESCs. Rho-associated kinase-dependent actin-myosin hyperactivation is an underlying mechanism that triggers apoptosis in dissociated hESCs; however, in this study, we show that the Ink4A-ARF-mediated senescence pathway is another mechanism to cause apoptosis in individualized hESCs. We show that P16(INK4A) and P14(ARF) are immediately induced in hESCs upon dissociation, but not in mouse ESCs...
December 13, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27926533/andrographolide-impedes-cancer-stemness-and-enhances-radio-sensitivity-in-oral-carcinomas-via-mir-218-activation
#6
Po-Yu Yang, Pei-Ling Hsieh, Tong Hong Wang, Cheng-Chia Yu, Ming-Yi Lu, Yi-Wen Liao, Tzu-Hsin Lee, Chih-Yu Peng
Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1-CD44- non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27920552/the-relationship-between-the-expression-of-usp22-bmi1-and-ezh2-in-hepatocellular-carcinoma-and-their-impacts-on-prognosis
#7
Run Zhai, Fang Tang, Jianhua Gong, Jing Zhang, Biao Lei, Bo Li, Yangchao Wei, Xingsi Liang, Bo Tang, Songqing He
Recent studies have shown that deubiquitination plays a key role in tumor progression, metastasis, resistance to chemotherapy drugs, and prognosis. In this study, we investigated the effects of the deubiquitinating enzyme USP22 on the expression of the drug-resistance genes BMI1 and EZH2 in hepatocellular carcinoma (HCC) and on prognosis. Downregulation of USP22 expression with interference ribonucleic acid in resistant HCC cell lines with high USP22 expression resulted in decreased BMI1 expression, but had no effect on EZH2 expression...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#8
Ying Yin, Xian Xue, Qian Wang, Ning Chen, Dengshun Miao
To explore whether polycomb repressor Bmi1 plays an important role in dentin and mandible development homeostasis by maintaining redox balance, 3-week-old Bmi1 gene knockout (Bmi1(-/-)) mice were treated with the antioxidant N-acetylcysteine (NAC) for 2 weeks in their drinking water and phenotypes of the tooth and mandibles were compared with vehicle-treated Bmi1(-/-) mice and wild-type mice by radiograph, histochemistry and immunohistochemistry. Alterations of oxidative stress, DNA damage, cell proliferation and cell cycle-related parameters were also examined in mandibles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27901496/cancer-initiating-cells-are-enriched-in-the-ca9-positive-fraction-of-primary-cervix-cancer-xenografts
#9
Delphine Tamara Marie-Egyptienne, Naz Chaudary, Tuula Kalliomäki, David William Hedley, Richard Peter Hill
Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900059/expression-and-survival-significance-of-b-cell-specific-moloney-murine-leukemia-virus-integration-site-1-and-matrix-metalloproteinase-9-in-non-small-cell-lung-cancer
#10
Mingkui Mu, Yang Song, Bin Zhang
One of the main challenges in lung cancer research is identifying patients at high risk of progression and metastasis following surgical resection. In the present study, the prognostic significance of B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and matrix metalloproteinase-9 (MMP9) in non-small-cell lung cancer (NSCLC) was evaluated. BMI1 and MMP9 expression in tumors from 132 surgical NSCLC patients [squamous cell carcinoma (SCC), n=79; and adenocarcinoma (AD), n=53] was evaluated by immunohistochemistry...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#11
M Hiraki, T Maeda, A Bouillez, M Alam, A Tagde, K Hinohara, Y Suzuki, T Markert, M Miyo, K Komura, R Ahmad, H Rajabi, D Kufe
B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a component of the polycomb repressive complex 1 (PRC1) complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27876791/an-amino-acid-based-oral-rehydration-solution-aa-ors-enhanced-intestinal-epithelial-proliferation-in-mice-exposed-to-radiation
#12
Liangjie Yin, Reshu Gupta, Lauren Vaught, Astrid Grosche, Paul Okunieff, Sadasivan Vidyasagar
Destruction of clonogenic cells in the crypt following irradiation are thought to cause altered gastrointestinal function. Previously, we found that an amino acid-based oral rehydration solution (AA-ORS) improved gastrointestinal function in irradiated mice. However, the exact mechanisms were unknown. Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that AA-ORS increased proliferation, maturation, and differentiation and improved electrolyte and nutrient absorption in irradiated mice...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#13
Hui Cheng, Heather Yin-Kuan Ang, Chadi A El Farran, Pin Li, Hai Tong Fang, Tong Ming Liu, Say Li Kong, Michael Lingzi Chin, Wei Yin Ling, Edwin Kok Hao Lim, Hu Li, Tara Huber, Kyle M Loh, Yuin-Han Loh, Bing Lim
Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase(+) megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27865367/circulating-tumor-stem-like-cells-in-oral-squamous-cell-carcinoma-an-unresolved-paradox
#14
Shanaya Patel, Kavan Shah, Sheefa Mirza, Kanisha Shah, Rakesh Rawal
OBJECTIVE: Circulating tumor cells (CTCs) are increasingly gaining importance due to their immense potential in enhancing diagnosis, prognosis and response to therapy in solid malignancies. Therefore, we aimed to comprehend the molecular diversity and critical role of this disseminated tumor population in OSCC. METHODOLOGY: CD44+ subpopulation was isolated using immuno-magnetic cell separation and their purity was validated using flow cytometry. Characterisation of self renewal potential and resistance to chemotherapy was assessed using tumor sphere forming and cytotoxicity assay...
November 2016: Oral Oncology
https://www.readbyqxmd.com/read/27863490/suberoylanilide-hydroxamic-acid-represses-glioma-stem-like-cells
#15
Che-Chia Hsu, Wen-Chang Chang, Tsung-I Hsu, Jr-Jiun Liu, Shiu-Hwa Yeh, Jia-Yi Wang, Jing-Ping Liou, Chiung-Yuan Ko, Kwang-Yu Chang, Jian-Ying Chuang
BACKGROUND: Glioma stem-like cells (GSCs) are proposed to be responsible for high resistance in glioblastoma multiforme (GBM) treatment. In order to find new strategies aimed at reducing GSC stemness and improving GBM patient survival, we investigated the effects and mechanism of a histone deacetylases (HDACs) inhibitor, suberoylanilide hydroxamic acid (SAHA), since HDAC activity has been linked to cancer stem-like cell (CSC) abundance and properties. METHODS: Human GBM cell lines were plated in serum-free suspension cultures allowed for sphere forming and CSC enrichment...
November 18, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27863389/nt1721-a-novel-epidithiodiketopiperazine-exhibits-potent-in-vitro-and-in-vivo-efficacy-against-acute-myeloid-leukemia
#16
Claudia M Kowolik, Min Lin, Jun Xie, Larry E Overman, David A Horne
Acute myeloid leukemia (AML) is an aggressive malignancy characterized by heterogeneous genetic and epigenetic changes in hematopoietic progenitors that lead to abnormal self-renewal and proliferation. Despite high initial remission rates, prognosis remains poor for most AML patients, especially for those harboring internal tandem duplication (ITD) mutations in the fms-related tyrosine kinase-3 (FLT3). Here, we report that a novel epidithiodiketopiperazine, NT1721, potently decreased the cell viability of FLT3-ITD+ AML cell lines, displaying IC50 values in the low nanomolar range, while leaving normal CD34+ bone marrow cells largely unaffected...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27846243/bacterially-associated-transcriptional-remodelling-in-a-distinct-genomic-subtype-of-colorectal-cancer-provides-a-plausible-molecular-basis-for-disease-development
#17
Katie S Lennard, Ryan W Goosen, Jonathan M Blackburn
The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC...
2016: PloS One
https://www.readbyqxmd.com/read/27832522/combined-treatments-with-a-retinoid-receptor-agonist-and-epigenetic-modulators-in-human-neuroblastoma-cells
#18
Viviane Rösner Almeida, Igor Araujo Vieira, Marienela Buendia, André Tesainer Brunetto, Lauro J Gregianin, Algemir Lunardi Brunetto, Fábio Klamt, Caroline Brunetto de Farias, Ana Lucia Abujamra, Patrícia Luciana da Costa Lopez, Rafael Roesler
Neuroblastoma (NB) is the most common extracranial solid childhood tumor accounting for around 15% of pediatric cancer deaths and most probably originates from a failure in the development of embryonic neural crest cells. Retinoids can inhibit the proliferation and stimulate differentiation of NB cells. In addition, epigenetic events involving changes in chromatin structure and DNA methylation can mediate the effects of retinoids; hence, the scope of this study is to investigate the use of retinoids and epigenetic drugs in NB cell lines...
November 10, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27827373/bmi1-regulates-prc1-architecture-and-activity-through-homo-and-hetero-oligomerization
#19
Felicia Gray, Hyo Je Cho, Shirish Shukla, Shihan He, Ashley Harris, Bohdan Boytsov, Łukasz Jaremko, Mariusz Jaremko, Borries Demeler, Elizabeth R Lawlor, Jolanta Grembecka, Tomasz Cierpicki
BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and emerging data support a role of BMI1 in cancer. The central domain of BMI1 is involved in protein-protein interactions and is essential for its oncogenic activity. Here, we present the structure of BMI1 bound to the polyhomeotic protein PHC2 illustrating that the central domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a β-hairpin conformation. Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27807665/a-new-transgenic-mouse-model-for-conditional-overexpression-of-the-polycomb-group-protein-ezh2
#20
Martijn A J Koppens, Ellen Tanger, Karim Nacerddine, Bart Westerman, Ji-Ying Song, Maarten van Lohuizen
The Polycomb Group protein EZH2 is upregulated in most prostate cancers, and its overexpression is associated with poor prognosis. Most insights into the functional role of EZH2 in prostate cancer have been gained using cell lines and EZH2 inactivation studies. However, the question remains whether overexpression of EZH2 can initiate prostate tumourigenesis or drive tumour progression. Appropriate transgenic mouse models that are required to answer such questions are lacking. We developed one such transgenic mouse model for conditional overexpression of Ezh2...
November 2, 2016: Transgenic Research
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