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Joseph E Gergely, Armond E Dorsey, Goberdhan P Dimri, Manjari Dimri
Polycomb group (PcG) protein BMI1 is an important regulator of oncogenic phenotype and is often overexpressed in several human malignancies including breast cancer. Aberrant expression of BMI1 is associated with metastasis and poor prognosis in cancer patients. At present, therapy reagents that can efficiently inhibit the expression of BMI1 are not very well known. Here, we report that Timosaponin A-III (TA-III), a steroidal saponin obtained from the rhizomes of an herb, Anemarrhena asphodeloides, strongly inhibits expression of BMI1 in breast cancer cells...
March 12, 2018: Molecular Carcinogenesis
Chenguang Bai, Xiaohong Liu, Jingjing Xu, Chen Qiu, Runqiu Wang, Jianming Zheng
Gastrointestinal stromal tumor (GIST) is believed to originate from intestinal cells of Cajal or their stem-cell precursors, and expresses stemness-related markers, such as CD117, CD34, DOG1 and nestin. To further characterize phenotypic features of GISTs, we examined expression profiles of a panel of stemness genes in GISTs, by analyzing existing gene expression profiling datasets. Our results showed that mRNA levels of B-lymphoma moloney murine leukaemia virus insertion region-1 (BMI1), kruppel-like factor 4 (KLF4), sal-like protein 4 (SALL4) and telomerase reverse transcriptase (TERT) were significantly unregulated in GISTs...
February 24, 2018: Human Pathology
Qinchao Hu, Tong Wu, Xiaobing Chen, Huan Li, Zhicheng Du, Yuantao Hao, Jianmin Peng, Shanshan Tai, Ming Song, Bin Cheng
Radiotherapy for nasopharyngeal carcinoma has been reported to cause second primary oral squamous cell carcinoma (s-OSCC). The prognosis and pathologic characteristic of s-OSCC are largely unknown. Bmi1 was associated with the repair of radiation-induced DNA damage, suggesting its possible involvement in the pathologic process of s-OSCC. Herein, we compared the prognosis between s-OSCC and primary OSCC (p-OSCC) and explored the involvement of Bmi1 in s-OSCC development. In this retrospective study, s-OSCC and p-OSCC patients were matched by propensity scores...
February 26, 2018: Cancer Medicine
Yang Song, Yong Chen, Yunqian Li, Xiaoyan Lyu, Jiayue Cui, Ye Cheng, Liyan Zhao, Gang Zhao
Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In spite of advances in diagnosis and therapy, the prognosis is still relatively poor. The invasive property of GBM is the major cause of death in patients. Epithelial-to-mesenchymal transition-like process (EMT-like process) is considered to play an important role in the invasive property. Metformin has been reported as a regulator of EMT-like process. In this study, we confirmed that metformin inhibited TGF-β1-induced EMT-like process and EMT-associated migration and invasion in LN18 and U87 GBM cells...
January 23, 2018: Oncotarget
Zhi-Jian Sun, Yi-Zhe Zhang, Fan Liu, Juan-Juan Chen, Dong-Xue Chen, Hong-Bao Liu, Liang Liang, Hua Han
Intestine is vulnerable to irradiation injury, which induces cell death and compromises regeneration of intestinal crypts. It is well accepted that cryptic stem cells, which are responsible for cryptic regeneration under physiological and pathological conditions, are controlled by multiple cell-intrinsic and environmental signals such as Notch signaling. Therefore in this study, we tested whether a soluble Notch ligand tethered to endothelial cells -- mD1R -- ¬¬¬the DSL domain of mouse Notch ligand Delta-like1 fused with a RGD motif, could protect cryptic cells from irradiation-induced intestinal injury...
February 14, 2018: Bioscience Reports
Yang Su, Zechao Wen, Qiyang Shen, Hua Zhang, Lei Peng, Guanglin Chen, Zhongxian Zhu, Chunxia Du, Hua Xie, Hongxing Li, Yankai Xia, Weibing Tang
Recently studies reported that long non-coding RNAs (lncRNAs) may take part in a lot of congenital diseases, meanwhile, Hirschsprung's disease (HSCR) is a major congenital digestive tract malformation. Nevertheless whether lncRNAs participate in the occurrence of HSCR and how it contributes to this disease are still unknown. LOC100507600 was selected from our gene expression microarray data obtained from bowel tissues from HSCR patients and negative controls. Subsequently, we used qRT-PCR to prove the result in 64 pairs of HSCR disease bowel stenosis tissues and negative controls...
February 12, 2018: Cell Cycle
Andrew Fesler, Hua Liu, Jingfang Ju
Despite advances in colon cancer treatments, resistance and recurrence remain a significant challenge in treating patients. Novel therapeutic strategies are in urgent need to overcome resistance and improve patient outcomes. MicroRNA based therapeutics have potential to help combat resistance. In this study, we have shown that low miR-15a expression correlates with poor patient prognosis. We have demonstrated the therapeutic potential of miR-15a in colon cancer. miR-15a inhibits several important genes (BCL2, BMI1, YAP1 and DCLK1), decreasing cancer progression and resistance...
January 5, 2018: Oncotarget
Yong Jin Cho, Soo Hee Kim, Eun Kyung Kim, Jung Woo Han, Kyoo-Ho Shin, Hyuk Hu, Kyung Sik Kim, Young Deuk Choi, Sunghoon Kim, Young Han Lee, Jin-Suck Suh, Joong Bae Ahn, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha, Sung-Taek Jung, Hyo Song Kim
BACKGROUND: Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification by H3K27me3. In the present study, we characterized the PRC expression pattern and its clinical implication in sarcoma. METHODS: Using immunohistochemistry, we analyzed PRC expression in 105 sarcoma patients with 5 subtypes: synovial sarcoma (n = 18), rhabdomyosarcoma (n = 28), Ewing sarcoma (n = 15), osteosarcoma (n = 30), and others (n = 14)...
February 7, 2018: BMC Cancer
Sen Zhu, Dongyu Zhao, Lin Yan, Weihua Jiang, Jung-Sun Kim, Bingnan Gu, Qipeng Liu, Rui Wang, Bo Xia, Jonathan C Zhao, Gang Song, Wenyi Mi, Rong-Fu Wang, Xiaobing Shi, Hung-Ming Lam, Xuesen Dong, Jindan Yu, Kaifu Chen, Qi Cao
BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression...
February 5, 2018: Nature Communications
Nibedita Patel, Koteswara Rao Garikapati, Venkata Krishna Kanth Makani, Ayikkara Drishya Nair, Namratha Vangara, Utpal Bhadra, Manika Pal Bhadra
Polycomb group (PcG) proteinB lymphoma Mo-MLV insertion region 1 homolog (BMI1) is a transcriptional repressor that plays an important role in human carcinogenesis. MicroRNAs (miRNAs) are endogenous small non-coding RNAsthat implicate a negative regulation on gene expression. Deregulation of the expression of miRNAs has been implicated in tumorigenesis. Here, we have shown that knock-down ofBMI1increases theexpression of tumor-suppressivemiRNAs. Elevated levels of expression of miR-200a, miR-200b, miR-15a, miR-429, miR-203were observed upon knock-down of BMI1...
2018: PloS One
Hasan Rajabi, Masayuki Hiraki, Donald Kufe
The PRC2 and PRC1 complexes are aberrantly expressed in human cancers and have been linked to decreases in patient survival. MUC1-C is an oncoprotein that is also overexpressed in diverse human cancers and is associated with a poor prognosis. Recent studies have supported a previously unreported function for MUC1-C in activating PRC2 and PRC1 in cancer cells. In the regulation of PRC2, MUC1-C (i) drives transcription of the EZH2 gene, (ii) binds directly to EZH2, and (iii) enhances occupancy of EZH2 on target gene promoters with an increase in H3K27 trimethylation...
January 30, 2018: Oncogene
Ting-Ting Yan, Lin-Lin Ren, Chao-Qin Shen, Zhen-Hua Wang, Ya-Nan Yu, Qian Liang, Jia-Yin Tang, Ying-Xuan Chen, Dan-Feng Sun, Witold Zgodziński, Marek Majewski, Piotr Radwan, Ilona Kryczek, Ming Zhong, Jinxian Chen, Qiang Liu, Weiping Zou, Hao-Yan Chen, Jie Hong, Jing-Yuan Fang
Colorectal cancer (CRC) includes an invasive stem-like/mesenchymal subtype but its genetic drivers, functional and clinical relevance are uncharacterized. Here we report the definition of an altered microRNA (miR) signature defining this subtype which includes a major genomic loss of miR-508. Mechanistic investigations showed that this microRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, BMI1 and BMI1. Loss of miR-508 in CRC was associated with upregulation of the novel hypoxia-induced long non-coding RNA AK000053...
January 26, 2018: Cancer Research
Feiyue Yu, Chuanyi Zhou, Hui Zeng, Yabing Liu, Shangfu Li
Aberrant activation of Wnt signaling plays a critical role in the development of colon cancer. BMI, a component of the polycomb repressive complex (PRC1), is upregulated in various types of cancer and contributes to epigenetic silencing of tumor suppressors. In this study, we showed that BMI1 is upregulated in colon cancer tissues and cell lines. Overexpression of BMI1 in primary epithelial colon cells promotes cellular growth and activates WNT pathway, while BMI1 silencing in colon cancer cells represses these effects...
January 11, 2018: Biochemical and Biophysical Research Communications
Jon Peñarando, Laura M López-Sánchez, Rafael Mena, Silvia Guil-Luna, Francisco Conde, Vanessa Hernández, Marta Toledano, Victoria Gudiño, Michela Raponi, Caroline Billard, Carlos Villar, César Díaz, José Gómez-Barbadillo, Juan De la Haba-Rodríguez, Kevin Myant, Enrique Aranda, Antonio Rodríguez-Ariza
BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts...
January 10, 2018: BMC Biology
Zhao Ya, Zeng Yue, Liu Dan, Lin Neng-Bo, Luo Yi, Miao Ying, Wan Qin
The aim of the work was to investigate the association between body weight change before and after delivery and development of nonmetabolic syndrome in Chinese females aged ≥40 years. We selected 789 participants without metabolic syndrome randomly from a baseline survey performed in Luzhou, China in 2011. We took the group with decreasing or no increasing body mass index difference during a pregnancy as "R-Body Mass Index 1" (n=286) and divided the group with increasing body mass index difference during a pregnancy into "R-Body Mass Index 2" (n=254) and "R-Body Mass Index 3" (n=249) based upon P50...
January 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Haihao Wang, Qiannan Guo, Guizhi Zhu, Shuo Zhu, Peiwen Yang, Mingsheng Zhang
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple solid tumors, its expression and function in hematological cancers including T-ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22 normal lymph node samples by real-time PCR analysis. The methylation levels in the promoter of miR-452 were determined using MethyLight assay. The effects of miR-452 overexpression on proliferation, cell cycle distribution, and tumorigenesis were explored...
January 10, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Diego Herrero, María Tomé, Susana Cañón, Francisco M Cruz, Rosa María Carmona, Encarna Fuster, Enrique Roche, Antonio Bernad
Accumulation of reactive oxygen species (ROS) is associated with several cardiovascular pathologies and with cell cycle exit by neonanatal cardiomyocytes, a key limiting factor in the regenerative capacity of the adult mammalian heart. The polycomb complex component BMI1 is linked to adult progenitors and is an important partner in DNA repair and redox regulation. We found that high BMI1 expression is associated with an adult Sca1+ cardiac progenitor sub-population with low ROS levels. In homeostasis, BMI1 repressed cell fate genes, including a cardiogenic differentiation program...
January 11, 2018: Cell Death and Differentiation
Levon M Khachigian
Yin Yang-1 (YY1) is a zinc finger protein and member of the GLI-Kruppel family that can activate or inactivate gene expression depending on interacting partners, promoter context and chromatin structure, and may be involved in the transcriptional control of ∼10% of the total mammalian gene set. A growing body of literature indicates that YY1 is overexpressed in multiple cancer types and that increased YY1 levels correlate with poor clinical outcomes in many cancers. However the role of YY1 in the promotion or suppression of tumor growth remains controversial and its regulatory effects may be tumor cell type dependent at least in experimental systems...
January 11, 2018: International Journal of Cancer. Journal International du Cancer
Solja Kalha, Bideep Shrestha, Maria Sanz Navarro, Kyle B Jones, Ophir D Klein, Frederic Michon
The outermost layer of the eye, the cornea, is renewed continuously throughout life. Stem cells of the corneal epithelium reside in the limbus at the corneal periphery and ensure homeostasis of the central epithelium. However, in young mice, homeostasis relies on cells located in the basal layer of the central corneal epithelium. Here, we first studied corneal growth during the transition from newborn to adult and assessed Keratin 19 (Krt19) expression as a hallmark of corneal maturation. Next, we set out to identify a novel marker of murine corneal epithelial progenitor cells before, during and after maturation, and we found that Bmi1 is expressed in the basal epithelium of the central cornea and limbus...
December 28, 2017: Stem Cells
Naif AlJohani, Suk-Jin Choi, Andrew G Day, Abdulmohsen Alhejaily, Shakeel Virk, Tara Baetz, David P LeBrun
Although generally indolent, follicular lymphoma (FL) sometimes pursues a more aggressive course leading to early death. B-cell-specific Mo-MLV insertion site-1 (BMI1) is a member of the polycomb group (PcG) proteins that confer stem cell properties through gene silencing. We used multi-channel immunofluorescence and automated image analysis to quantify BMI1 selectively in the nuclei of FL-derived B-cells in routine biopsy specimens. Applying this assay to 109 pretreatment FL biopsy samples demonstrates a significant association between abundant BMI1 and reduced overall survival (p = ...
December 18, 2017: Leukemia & Lymphoma
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