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https://www.readbyqxmd.com/read/28790065/gsk-3-inhibition-drives-maturation-of-nk-cells-and-enhances-their-antitumor-activity
#1
Frank Cichocki, Bahram Valamehr, Ryan Bjordahl, Bin Zhang, Betsy Rezner, Paul Rogers, Svetlana Gaidarova, Stacey K Moreno, Katie Tuininga, Phillip Dougherty, Valarie McCullar, Peter Howard, Dhifaf Sarhan, Emily Taras, Heinrich Schlums, Stewart E Abbot, Daniel Shoemaker, Yenan T Bryceson, Bruce R Blazar, Scott Wolchko, Sarah Cooley, Jeffrey S Miller
Maturation of human natural killer cells (NK cells) as defined by accumulation of cell surface expression of CD57 is associated with increased cytotoxic character and TNF and IFN-γ production upon target cell recognition. Notably, multiple studies point to a unique role for CD57(+) NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacological inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL-15 greatly enhances CD57 upregulation and late-stage maturation...
August 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28783176/short-stretches-of-rare-codons-regulate-translation-of-the-transcription-factor-zeb2-in-cancer-cells
#2
W R Wan Makhtar, G Browne, A Karountzos, C Stevens, Y Alghamdi, A R Bottrill, S Mistry, E Smith, M Bushel, J H Pringle, A E Sayan, E Tulchinsky
Two proteins comprising the ZEB family of zinc finger transcription factors, ZEB1 and ZEB2, execute EMT programs in embryonic development and cancer. By studying regulation of their expression, we describe a novel mechanism that limits ZEB2 protein synthesis. A protein motif located at the border of the SMAD-binding domain of ZEB2 protein induces ribosomal pausing and compromises protein synthesis. The function of this protein motif is dependent on stretches of rare codons, Leu(UUA)-Gly(GGU)-Val(GUA). Incorporation of these triplets in the homologous region of ZEB1 does not affect protein translation...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28783105/viral-ubiquitin-ligase-stimulates-selective-host-microrna-expression-by-targeting-zeb-transcriptional-repressors
#3
Gabriel Lutz, Igor Jurak, Eui Tae Kim, Ju Youn Kim, Michael Hackenberg, Andrew Leader, Michelle L Stoller, Donna M Fekete, Matthew D Weitzman, Donald M Coen, Angus C Wilson
Infection with herpes simplex virus-1 (HSV-1) brings numerous changes in cellular gene expression. Levels of most host mRNAs are reduced, limiting synthesis of host proteins, especially those involved in antiviral defenses. The impact of HSV-1 on host microRNAs (miRNAs), an extensive network of short non-coding RNAs that regulate mRNA stability/translation, remains largely unexplored. Here we show that transcription of the miR-183 cluster (miR-183, miR-96, and miR-182) is selectively induced by HSV-1 during productive infection of primary fibroblasts and neurons...
August 7, 2017: Viruses
https://www.readbyqxmd.com/read/28777859/-delineating-a-case-with-a-complex-karyotype-by-using-combined-genetic-techniques
#4
Ning Han, Lu Kuang, Bing Zhu, Liang Hua, Wanling Li
OBJECTIVE: To explore the pathogenesis of a child with growth retardation, liver damage and congenital heart disease. METHODS: G-banded chromosomal karyotyping, high-throughput next-generation sequencing (HT-NGS)and fluorescence in situ hybridization(FISH) were used to characterize the structural chromosomal aberration. RESULTS: The child was found to have a karyotype of 46, XX, t(1;2) (q25;q21), t(7;20) (q21;p13). HT-NGS has detected a microdeletion at 2q21...
August 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#5
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28739727/mir-141-inhibits-proliferation-and-migration-of-colorectal-cancer-sw480-cells
#6
Zhi H Long, Zhi G Bai, Jian N Song, Zhi Zheng, Jun Li, Jun Zhang, Jun Cai, Hong W Yao, Jin Wang, Ying C Yang, Jie Yin, Zhong T Zhang
BACKGROUND: This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC). MATERIALS AND METHODS: SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28736185/effect-of-coa-cl-on-transforming-growth-factor-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-rle-abca3-cells
#7
Masashi Kawami, Junya Deguchi, Ryoko Yumoto, Norikazu Sakakibara, Ikuko Tsukamoto, Ryoji Konishi, Mikihisa Takano
Transforming growth factor (TGF)-β1 has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) in pathological conditions such as cancer and organ fibrosis. In this study, we examined the effect of a novel nucleic acid analog, COA-Cl, on TGF-β1-induced EMT using RLE/Abca3, a cell line having alveolar type II cell-like phenotype. Changes in the cell morphology consistent with EMT were induced by TGF-β1, whereas, this response was suppressed by co-treatment of the cells with COA-Cl...
May 17, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28690488/a-novel-partial-duplication-of-zeb2-and-review-of-zeb2-involvement-in-mowat-wilson-syndrome
#8
Adrianne L Baxter, Jay L Vivian, R Tanner Hagelstrom, Waheeda Hossain, Wendy L Golden, E Robert Wassman, Rena J Vanzo, Merlin G Butler
Mowat-Wilson syndrome is a rare genetic condition characterized by intellectual disability, structural anomalies, and dysmorphic features. It is caused by haploinsufficiency of the ZEB2 gene in chromosome 2q22.3. Over 180 distinct mutations in ZEB2 have been reported, including nonsense and missense point mutations, deletions, and large chromosomal rearrangements. We report on a 14-year-old female with a clinical diagnosis of Mowat-Wilson syndrome. Chromosomal microarray identified a novel de novo 69-kb duplication containing exons 1 and 2 of the ZEB2 gene...
June 2017: Molecular Syndromology
https://www.readbyqxmd.com/read/28680141/the-lincrna-ror-mir-145-axis-promotes-invasion-and-metastasis-in-hepatocellular-carcinoma-via-induction-of-epithelial-mesenchymal-transition-by-targeting-zeb2
#9
Chen Li, Lu Lu, Bing Feng, Kai Zhang, Siqi Han, Daorong Hou, Longbang Chen, Xiaoyuan Chu, Rui Wang
Emerging evidence show that long noncoding RNAs (lncRNAs) play critical roles in tumor development. LincRNA-ROR (linc-ROR) is known to promote tumor progress in several human cancers, including hepatocellular carcinoma (HCC). Nevertheless, the roles of linc-ROR in HCC metastasis and its underlying mechanisms remain fully unclear. In the present study, we showed that linc-ROR was upregulated in HCC tissues and high linc-ROR expression level predicted poor prognosis. Functionally, linc-ROR significantly induced epithelial-mesenchymal transition (EMT), and increased in vitro invasion and in vivo metastasis of HCC cells...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28677740/isoform-switch-of-cd44-induces-different-chemotactic-and-tumorigenic-ability-in-gallbladder-cancer
#10
Takeshi Miwa, Takuya Nagata, Hirofumi Kojima, Shinichi Sekine, Tomoyuki Okumura
Gallbladder cancer (GBC) is one of the most unfavorable prognostic tumor, and immediate growth and distant metastasis are important factors associated with the poor prognosis of patients with this disease. Standard and variant isoforms of CD44 are associated with tumor growth, metastasis, and epithelial-mesenchymal transition (EMT), although their roles in GBC are unclear. We investigated the relationship between the CD44 isoforms with EMT, chemotaxis, and tumorigenicity. We analyzed CD44 expression in the GBC cell line NOZ and found that it comprises a major population that expressed CD44std+/CD44v9- (CD44s) and the minor population that expressed CD44std-/CD44v9+ (CD44v)...
July 3, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28675952/a-novel-fine-tuning-scheme-of-mir-200c-in-modulating-lung-cell-redox-homeostasis
#11
Yi-Hsuan Wu, Hsin-Ru Lin, Ying-Hsuan Lee, Pin-Hao Huang, Huei-Chung Wei, Arnold Stern, Daniel Tsun-Yee Chiu
Oxidative stress induces miR-200c, the predominant microRNA (miRNA) in lung tissues; however, the antioxidant role and biochemistry of such induction have not been clearly defined. Therefore, a lung adenocarcinoma cell line (A549) and a normal lung fibroblast (MRC-5) were used as models to determine the effects of miR-200c expression on lung antioxidant response. Hydrogen peroxide (H2O2) upregulated miR-200c, whose overexpression exacerbated the decrease in cell proliferation, retarded the progression of cells in the G2/M-phase, and increased oxidative stress upon H2O2 stimulation...
July 4, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28675122/mir-204-zeb2-axis-functions-as-key-mediator-for-malat1-induced-epithelial-mesenchymal-transition-in-breast-cancer
#12
Yuzhou Wang, Yijin Zhou, Zhicheng Yang, Baoying Chen, Wennan Huang, Yongyuan Liu, Ying Zhang
Long non-coding RNAs recently were identified as key mediators of cancer metastasis. This study provided evidence that long non-coding RNA MALAT1 was up-regulated in breast cancer tissues and cell lines. MALAT1 promoted cancer cell invasion through inducing epithelial-mesenchymal transition. Interestingly, we revealed there was a reciprocal repression between MALAT1 and miR-204. ZEB2 was identified as a downstream target of miR-204 and MALAT1 exerted its function mainly through the miR-204/ZEB2 axis. Our findings suggested that MALAT1 may serve as a new diagnostic biomarker and therapy target for breast cancer...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28670373/zeb2-promotes-tumor-metastasis-and-correlates-with-poor-prognosis-of-human-colorectal-cancer
#13
Ming-Zhe Li, Jing-Jing Wang, Shi-Bin Yang, Wen-Feng Li, Long-Bin Xiao, Yu-Long He, Xin-Ming Song
Colorectal cancer remains the most common cause of cancer-related deaths worldwide and it continues to lack an effective treatment. Here, we found that zinc finger E-box binding homeobox 2 (ZEB2) was overexpressed in several colorectal cancer cell lines and colorectal cancer specimens relative to adjacent non-cancerous tissues. Although ZEB2 has been reported to be associated with several tumors, its involvement in colorectal cancer progression remains unclear. In this study, we investigated the biological functions and molecular mechanisms of ZEB2 underlying colorectal carcinoma metastasis and angiogenesis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28646172/dacomitinib-a-pan-inhibitor-of-erbb-receptors-suppresses-growth-and-invasive-capacity-of-chemoresistant-ovarian-carcinoma-cells
#14
Majid Momeny, Ghazaleh Zarrinrad, Farima Moghaddaskho, Arash Poursheikhani, Ghazaleh Sankanian, Azam Zaghal, Shahab Mirshahvaladi, Fatemeh Esmaeili, Haniyeh Eyvani, Farinaz Barghi, Zahra Sabourinejad, Zivar Alishahi, Hassan Yousefi, Reza Ghasemi, Leila Dardaei, Davood Bashash, Bahram Chahardouli, Ahmad R Dehpour, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28635228/-mechanism-of-long-non-coding-rna-metastasis-associated-lung-adenocarcinoma-transcript-1-induced-invasion-and-metastasis-of-esophageal-cancer-cell-ec-109
#15
Q Q Zhang, Y H Cui, Y Wang, W Z Kou, F Cao, X J Cao, Z H Miao, X H Kang
Objective: To investigate the effect and mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1, (LncRNA-MALAT1) on invasion and metastasis of esophageal cancer cell EC-109. Methods: EC-109 cells were transfected with lentiviral vector carrying short hairpin RNA of MALAT1( shRNA-MALAT1) or a nonspecific shRNA control (shRNA-control). The expressions of MALAT1, microRNA-200a, ZEB1 and ZEB2 were detected by qRT-PCR. The effect of shRNA-MALAT1 on invasion of EC-109 cells was determined by transwell assay...
June 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28635133/critical-role-of-glioma-associated-oncogene-homolog-1-in-maintaining-invasive-and-mesenchymal-like-properties-of-melanoma-cells
#16
I Ketut Gunarta, Rong Li, Ryota Nakazato, Ryusuke Suzuki, Jambaldorj Boldbaatar, Takeshi Suzuki, Katsuji Yoshioka
Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non-invasive and invasive potential, and microphthalmia-associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma-associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear...
August 2017: Cancer Science
https://www.readbyqxmd.com/read/28623900/characterization-of-microrna-200-pathway-in-ovarian-cancer-and-serous-intraepithelial-carcinoma-of-fallopian-tube
#17
Junzheng Yang, Yilan Zhou, Shu-Kay Ng, Kuan-Chun Huang, Xiaoyan Ni, Pui-Wah Choi, Kathleen Hasselblatt, Michael G Muto, William R Welch, Ross S Berkowitz, Shu-Wing Ng
BACKGROUND: Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors...
June 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28621681/overexpression-of-emt-inducing-transcription-factors-as-a-potential-poor-prognostic-factor-for-hepatocellular-carcinoma-in-asian-populations-a-meta-analysis
#18
Tao Wan, Tianwei Zhang, Xiaoying Si, Yanming Zhou
BACKGROUND AND OBJECTIVES: The clinical relevance of epithelial to mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) progression has been highlighted during the last decade. The zinc finger E-box binding homeobox (ZEB) family, the zinc-finger transcriptional repressor (SNAI) family, and the basic helix-loop-helix transcription factor (Twist) family, known as the prominent EMT-inducing transcription factors (EMT-TFs), played a crucial role in the process of EMT. Here, this meta-analysis aimed to evaluate the prognostic value of EMT-TFs high expression in patients with HCC after hepatectomy...
June 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618162/zeb1-regulated-inflammatory-phenotype-in-breast-cancer-cells
#19
Akihiro Katsura, Yusuke Tamura, Satoshi Hokari, Mayumi Harada, Masato Morikawa, Tsubasa Sakurai, Kei Takahashi, Anna Mizutani, Jun Nishida, Yuichiro Yokoyama, Yasuyuki Morishita, Takashi Murakami, Shogo Ehata, Kohei Miyazono, Daizo Koinuma
Zinc finger E-box binding protein 1 (ZEB1) and ZEB2 induce epithelial-mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1-regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation-sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1-bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the down-regulation of genes encoding inflammatory cytokines related to poor prognosis in cancer patients, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines...
June 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28617555/correlation-analysis-of-mir-200b-mir-200c-and-mir-141-with-liver-metastases-in-colorectal-cancer-patients
#20
S-H Zhu, X-C He, L Wang
OBJECTIVE: To investigate correlation relationship between serum miR-200b, miR-200c, miR-141 levels with liver metastases in colorectal cancer patients. PATIENTS AND METHODS: A total of 85 colorectal cancer patients with liver metastases and 54 colorectal cancer patients without liver metastases were divided into experimental group and control. Serum sample was collected before surgery and tested by Real-time PCR to evaluate miR-200b, miR-200c, miR-141 expressions...
May 2017: European Review for Medical and Pharmacological Sciences
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