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https://www.readbyqxmd.com/read/27926516/frequent-silencing-of-the-candidate-tumor-suppressor-trim58-by-promoter-methylation-in-early-stage-lung-adenocarcinoma
#1
Koichiro Kajiura, Kiyoshi Masuda, Takuya Naruto, Tomohiro Kohmoto, Miki Watabnabe, Mitsuhiro Tsuboi, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku, Issei Imoto
In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926508/microrna-497-inhibits-thyroid-cancer-tumor-growth-and-invasion-by-suppressing-bdnf
#2
Peisong Wang, Xianying Meng, Yan Huang, Zhi Lv, Jia Liu, Guimin Wang, Wei Meng, Shuai Xue, Qiang Zhang, Pengju Zhang, Guang Chen
miR-497 reportedly plays critical roles in tumor development and progression in many types of cancers. We therefore investigated the function and underlying mechanism of miR-497 in thyroid cancer. We found that miR-497 is downregulated in thyroid cancer tissues, and that miR-497 levels are negatively correlated with advanced clinical stage and lymph node metastasis. Overexpressed miR-497 suppressed thyroid cancer cell proliferation, colony formation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926503/foxd3-is-a-tumor-suppressor-of-colon-cancer-by-inhibiting-egfr-ras-raf-mek-erk-signal-pathway
#3
Kun Li, Qunfeng Guo, Jun Yang, Hui Chen, Kewen Hu, Juan Zhao, Shunxin Zheng, Xiufeng Pang, Sufang Zhou, Yongyan Dang, Lei Li
Forkhead box D3 (FOXD3), as a transcriptional repressor, is well known to be involved in the regulation of development. Although FoxD3 is associated with several cancers, its role in colon cancer and the underlying mechanism are still unclear. Here, we first showed that FOXD3 knockdown dramatically increased the proliferation of human colon cancer cells, enhanced cell invasive ability and inhibited cell apoptosis. In vivo xenograft studies confirmed that the FOXD3-knockdown cells were more tumorigenic than the controls...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926489/suppression-of-immune-regulatory-cells-with-combined-therapy-of-celecoxib-and-sunitinib-in-renal-cell-carcinoma
#4
Qi Zhao, Jianming Guo, Guomin Wang, Yiwei Chu, Xiaoyi Hu
OBJECTIVE: To observe the the potential benefit of sunitinib in combination with cyclooxygenase-2(COX-2) inhibitor in renal cell carcinoma therapy. METHODS: 769-p cell lines were treated with sunitinib, celecoxib, or in combination at different concentrations respectively. We investigated the expression of granulocyte-macrophage colony stimulating factor (GM-CSF) in 769-p and cell proliferation in vitro. BALB/c mice implanted with Renca cells were divided into 4 groups and administered orally by gavage with sunitinib, COX-2 inhibitor (celecoxib) monotherapy or combination, and PBS respectively...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924503/mir-206-inhibits-renal-cell-cancer-growth-by-targeting-gak
#5
Chao Wei, Shen Wang, Zhang-Qun Ye, Zhi-Qiang Chen
Renal cell cancer (RCC) remains one of the most lethal types of cancer in adults. MicroRNAs (miRNAs) play key roles in the pathogenesis of RCC. The role of miR-206 in RCC has not been fully understood. The purpose of this study was to examine the role of miR-206 in the regulation of proliferation and metastasis of RCC and the possible mechanism. miR-206 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RCC cell lines (786-O and OS-RC-2 cells) and clinical samples...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27924500/mir-124-modulates-gefitinib-resistance-through-snai2-and-stat3-in-non-small-cell-lung-cancer
#6
Fa-Yong Hu, Xiao-Nian Cao, Qin-Zi Xu, Yu Deng, Sen-Yan Lai, Jing Ma, Jun-Bo Hu
Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer (NSCLC). Unfortunately, most NSCLC patients inevitably develop gefitinib resistance during treatment. In addition to EGFR mutation status, the mechanisms involved are largely unknown. In this study, we showed that miR-124, a tumor suppressor, was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines. In addition, the miR-124 depletion induced gefitinib resistance, and miR-124 overexpression sensitized gefitinib-resistant cells to gefitinib...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27924482/identification-of-small-molecule-modulators-of-microrna-by-library-screening
#7
Zhangang Xiao, Yangchao Chen
MicroRNAs (miRNAs) function as oncogenes or tumor suppressors and are dysregulated in cancer. miRNAs therefore represent promising therapeutic targets for cancer. Small molecules that could modulate the expression of miRNAs would thus have potential as anticancer agents. Library screening of small molecules targeting miRNAs is a useful technology platform for anticancer drug development. Here, we describe a hepatocellular carcinoma (HCC) cell-based luciferase reporter system which could be used to screen for small molecule modulators of tumor suppressor microRNA-34a...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924478/evaluating-synergistic-effects-of-mir-34a-mimics-in-combination-with-other-therapeutic-agents-in-cultured-non-small-cell-lung-cancer-cells
#8
Jane Zhao, Andreas G Bader
Tumor suppressor miRNAs such as miR-34a inhibit tumor growth by simultaneously regulating the expression of multiple important oncogenes across multiple oncogenic pathways and, therefore, provide a strong rationale for developing therapeutic miRNA mimics in combination with other therapeutic cancer agents to augment drug sensitivity. Here, we describe the experimental approach for evaluating miRNA and drug combinations using the "fixed ratio" method in cultured non-small cell lung cancer cells.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924011/roles-for-aprin-pds5b-in-homologous-recombination-and-in-ovarian-cancer-prediction
#9
Anthony M Couturier, Hubert Fleury, Anne-Marie Patenaude, Victoria L Bentley, Amélie Rodrigue, Yan Coulombe, Joshi Niraj, Joris Pauty, Jason N Berman, Graham Dellaire, Javier M Di Noia, Anne-Marie Mes-Masson, Jean-Yves Masson
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923995/homologous-recombination-in-budding-yeast-expressing-the-human-rad52-gene-reveals-a-rad51-independent-mechanism-of-conservative-double-strand-break-repair
#10
Glenn M Manthey, Alissa D Clear, Lauren C Liddell, Maria C Negritto, Adam M Bailis
RAD52 is a homologous recombination (HR) protein that is conserved from bacteriophage to humans. Simultaneously attenuating expression of both the RAD52 gene, and the HR and tumor suppressor gene, BRCA2, in human cells synergistically reduces HR - indicating that RAD52 and BRCA2 control independent mechanisms of HR. We have expressed the human RAD52 gene (HsRAD52) in budding yeast strains lacking the endogenous RAD52 gene and found that HsRAD52 supports repair of DNA double-strand breaks (DSB) by a mechanism of HR that conserves genome structure...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923837/the-nci-60-methylome-and-its-integration-into-cellminer
#11
William C Reinhold, Sudhir Varma, Margot Sunshine, Vinodh Rajapakse, Augustin Luna, Kurt W Kohn, Holly Stevenson, Yonghong Wang, Holger Heyn, Vanesa Nogales, Sebastian Moran, David J Goldstein, James H Doroshow, Paul S Meltzer, Manel Esteller, Yves Pommier
A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (~21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and microRNA transcripts, DNA copy number, and protein levels. Here we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923836/the-swi-snf-complex-protein-snr1-is-a-tumor-suppressor-in-drosophila-imaginal-tissues
#12
Gengqiang Xie, Hanqing Chen, Dongyu Jia, Zhiqiang Shu, William Hunt Palmer, Yi-Chun Huang, Xiankun Zeng, Steven X Hou, Renjie Jiao, Wu-Min Deng
Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923833/an-essential-role-of-maspin-in-embryogenesis-and-tumor-suppression
#13
Sijana H Dzinic, M Margarida Bernardo, Xiaohua Li, Rodrigo Fernandez-Valdivia, Ye-Shih Ho, Qing-Sheng Mi, Sudeshna Bandyopadhyay, Fulvio Lonardo, Semir Vranic, Daniel Oliveira, R Daniel Bonfil, Gregory Dyson, Kang Chen, Almasa Omerovic, Xiujie Sheng, Xiang Han, Dinghong Wu, Xinling Bi, Dzenana Cabaravdic, Una Jakupovic, Marian Wahba, Aaron Pang, Deanna Harajli, Wael Sakr, Shijie Sheng
Maspin (SerpinB5) is an epithelial-specific tumor suppressor gene product that displays context-dependent cellular functions. Maspin-deficient mouse models created to date have not definitively established maspin functions critical for cancer suppression. In this study, we generated a mouse strain in which exon 4 of the Maspin gene was deleted, confirming its essential role in development but also enabling a breeding scheme to bypass embryonic lethality. Phenotypic characterization of this viable strain established that maspin deficiency was associated with a reduction in maximum body weight and a variety of context-dependent epithelial abnormalities...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923832/ese3-inhibits-pancreatic-cancer-metastasis-by-upregulating-e-cadherin
#14
Tiansuo Zhao, Wenna Jiang, Xiuchao Wang, Hongwei Wang, Chen Zheng, Yang Li, Yan Sun, Chongbiao Huang, Zhi-Bo Han, Shengyu Yang, Zhiliang Jia, Keping Xie, He Ren, Jihui Hao
The ETS family transcription factor ESE3 is a crucial element in differentiation and development programs for many epithelial tissues. Here we report its role as a tumor suppressor in pancreatic cancer. We observed drastically lower ESE3 expression in pancreatic ductal adenocarcinomas (PDAC) compared to adjacent normal pancreatic tissue. Reduced expression of ESE3 in PDAC correlated closely with an increase in lymph node metastasis and vessel invasion and a decrease in relapse-free and overall survival in patients...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923803/whole-exome-sequencing-validates-a-preclinical-mouse-model-for-the-prevention-and-treatment-of-cutaneous-squamous-cell-carcinoma
#15
Elena V Knatko, Brandon Praslicka, Maureen Higgins, Alan Evans, Karin J Purdie, Catherine A Harwood, Charlotte M Proby, Aikseng Ooi, Albena T Dinkova-Kostova
Cutaneous squamous cell carcinomas (cSCC) are among the most common and highly mutated human malignancies. Solar UV radiation is the major factor in the etiology of cSCC. Whole exome sequencing of 18 microdissected tumor samples (cases) derived from SKH-1 hairless mice that had been chronically exposed to solar-simulated UV (SSUV) radiation showed a median point mutation (single nucleotide polymorphism, SNP) rate of 155 per megabase. The majority (78.6%) of the SNPs are C.G>T.A transitions, a characteristic UVR-induced mutational signature...
December 6, 2016: Cancer Prevention Research
https://www.readbyqxmd.com/read/27923712/regulation-of-microrna-1-mir-1-expression-in-human-cancer
#16
REVIEW
Chao Han, Jacson K Shen, Francis J Hornicek, Quancheng Kan, Zhenfeng Duan
MicroRNAs (miRs) have been found to play important roles in tumorigenesis, apoptosis, metastasis, and drug resistance in cancer. Among a number of miRs, miR-1 was shown to be predominantly downregulated in almost all examined human cancers. As a tumor suppressor miR involved in post-transcriptional regulation of crucial tumor associated gene expression, miR-1 represents a promising target for anticancer therapy. Re-expression of miR-1 can suppress cancer cell proliferation, promote apoptosis, and reverse drug resistance in cancers both in vitro and in vivo...
December 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27922689/rb-knockdown-accelerates-bladder-cancer-progression-through-e2f3-activation
#17
Jiang-Ping Wang, Yong Jiao, Cheng-Yuan Wang, Zhi-Bin Xu, Bo Zhang
Bladder cancer is one of the most common cancers diagnosed in the world and leads to significant mortality and morbidity among affected patients. The retinoblastoma (Rb) protein is a main tumor suppressor, controlling cellular responses to potentially oncogenic stimulation. E2F3 was invariably disrupted in different human cancers for its central role in the control of cellular proliferation. Here, we investigated how Rb is integrated to control bladder cancer progression through E2F3 and p53 regulation. The results exhibit that Rb expression is lower in patients with bladder tumor, while E2F3 level is high...
December 6, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27922687/immature-myeloid-derived-suppressor-cells-a-bridge-between-inflammation-and-cancer-review
#18
Caterina Musolino, Alessandro Allegra, Govanni Pioggia, Sebastiano Gangemi
Chronic inflammation is considered to be one of the hallmarks of tumor initiation and progression. Changes occurring in the microenvironment of progressing tumors resemble the process of chronic inflammation, which begins with ischemia followed by interstitial and cellular edema, appearance of immune cells, growth of blood vessels and tissue repair, and development of inflammatory infiltrates. Moreover, long‑term production and accumulation of inflammatory factors lead to local and systemic immunosuppression associated with cancer progression...
December 5, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922669/upregulation-of-smad4-by-mzf1-inhibits-migration-of-human-gastric-cancer-cells
#19
Jin-Hee Lee, Sung-Su Kim, Hun Seok Lee, Sungyoul Hong, Nirmal Rajasekaran, Li-Hui Wang, Joon-Seok Choi, Young Kee Shin
SMAD4 is a tumor suppressor that is frequently inactivated in many types of cancer. The role of abnormal expression of SMAD4 has been reported in developmental processes and the progression of various human cancers. The expression level of SMAD4 has been related to the survival rate in gastric cancer patients. However, the molecular mechanism underlying transcriptional regulation of SMAD4 remains largely unknown. In the present study, we characterized the promoter region of SMAD4 and identified myeloid zinc finger 1 (MZF1), as a putative transcription factor...
December 6, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27920939/epigenetic-mechanisms-drive-the-progression-of-neurofibromas-to-malignant-peripheral-nerve-sheath-tumors
#20
REVIEW
Krish Suresh, Tamara Kliot, Andrea Piunti, Michel Kliot
THINKING OUTSIDE THE BOX: The polycomb repressive complex 2 (PRC2) is a histone methyltransferase complex known to repress gene expression. There is a large body of experimental evidence that supports its role in promoting tumorigenicity by suppressing tumor suppressor genes. Here, we discuss the surprising findings that, in neurofibromas, it may have a completely different role as a tumor suppressor; mutations of PRC2 lead to conversion of benign neurofibromas into malignant peripheral nerve sheath tumors (MPNSTs) by de-repressing and thereby activating genes driving cell growth and development...
2016: Surgical Neurology International
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