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Tumor suppressor

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https://www.readbyqxmd.com/read/29141234/elevated-p53-activities-restrict-differentiation-potential-of-microrna-deficient-pluripotent-stem-cells
#1
Zhong Liu, Cheng Zhang, Maria Skamagki, Alireza Khodadadi-Jamayran, Wei Zhang, Dexin Kong, Chia-Wei Chang, Jingyang Feng, Xiaosi Han, Tim M Townes, Hu Li, Kitai Kim, Rui Zhao
Pluripotent stem cells (PSCs) deficient for microRNAs (miRNAs), such as Dgcr8(-/-) or Dicer(-/-) embryonic stem cells (ESCs), contain no mature miRNA and cannot differentiate into somatic cells. How miRNA deficiency causes differentiation defects remains poorly understood. Here, we report that miR-302 is sufficient to enable neural differentiation of differentiation-incompetent Dgcr8(-/-) ESCs. Our data showed that miR-302 directly suppresses the tumor suppressor p53, which is modestly upregulated in Dgcr8(-/-) ESCs and serves as a barrier restricting neural differentiation...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29141220/phosphorylation-and-ubiquitination-regulate-protein-phosphatase-5-activity-and-its-prosurvival-role-in-kidney-cancer
#2
Natela Dushukyan, Diana M Dunn, Rebecca A Sager, Mark R Woodford, David R Loiselle, Michael Daneshvar, Alexander J Baker-Williams, John D Chisholm, Andrew W Truman, Cara K Vaughan, Timothy A Haystead, Gennady Bratslavsky, Dimitra Bourboulia, Mehdi Mollapour
The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity. Here, we show an "on/off switch" mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141020/genomic-analysis-of-atypical-fibroxanthoma
#3
Kevin Lai, Catherine A Harwood, Karin J Purdie, Charlotte M Proby, Irene M Leigh, Namita Ravi, Thaddeus W Mully, Lionel Brooks, Priscilla M Sandoval, Michael D Rosenblum, Sarah T Arron
Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found...
2017: PloS One
https://www.readbyqxmd.com/read/29140794/targeted-elimination-of-senescent-ras-transformed-cells-by-suppression-of-mek-erk-pathway
#4
Elena Y Kochetkova, Galina I Blinova, Olga A Bystrova, Marina G Martynova, Valery A Pospelov, Tatiana V Pospelova
The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance. We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras-transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition...
November 14, 2017: Aging
https://www.readbyqxmd.com/read/29139296/differential-content-of-proteins-mrnas-and-mirnas-suggests-that-mdsc-and-their-exosomes-may-mediate-distinct-immune-suppressive-functions
#5
Lucia Geis-Asteggiante, Ashton T Belew, Virginia K Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Nagib M El-Sayed, Catherine Fenselau
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC...
November 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29138862/liver-kinase%C3%A2-b1-restoration-promotes-exosome-secretion-and-motility-of-lung-cancer-cells
#6
Cheng Zhang, Xiang Xiao, Minyi Chen, Hitham Aldharee, Yanfang Chen, Weiwen Long
Liver kinase B1 (LKB1) regulates a variety of cellular functions, including cell polarity, energy metabolism and cell growth, by targeting multiple signaling pathways such as AMPK/mTOR and p53. LKB1 functions as a tumor suppressor in sporadic cancers including lung cancer. Extracellular vesicles such as exosomes secreted by cancer cells modulate the tumor microenvironment and progression by targeting both tumor cells (autocrine actions) and other types of cells associated with tumors (paracrine actions). While the roles of LKB1 in cellular signaling in general is well-studied, its specific role in exosome-mediated signaling remains to be explored...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138857/mir%C3%A2-218-inhibits-the-proliferation-of-human-glioma-cells-through-downregulation-of-yin-yang-1
#7
Yong Gao, Laisheng Sun, Zicheng Wu, Chengmin Xuan, Junxia Zhang, Yongping You, Xincheng Chen
Malignant glioma is the most common cancer type of the nervous system and the mechanisms driving the occurrence and development remain unclear, preventing effective treatment of this disease. Therefore, novel and efficient therapies for glioma are required. MicroRNAs (miRNAs) are small non‑coding RNAs that act as oncogenes or tumor suppressors in human cancer. In the present study, it was confirmed that Yin Yang‑1 (YY1), a transcription factor that is part of the polycomb group protein (PcG) family, is a direct target of miR‑218 in human glioma cells...
November 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138825/utility-of-mir%C3%A2-133a%C3%A2-3p-as-a-diagnostic-indicator-for-hepatocellular-carcinoma-an-investigation-combined-with-geo-tcga-meta%C3%A2-analysis-and-bioinformatics
#8
Hai-Wei Liang, Xia Yang, Dong-Yue Wen, Li Gao, Xiang-Yu Zhang, Zhi-Hua Ye, Jie Luo, Zu-Yun Li, Yun He, Yu-Yan Pang, Gang Chen
Increasing evidence has demonstrated that microRNA (miR)‑133a‑3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR‑133a‑3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138803/toll-like-receptors-tlr1-2-tlr6-and-muc5b-as-binding-interaction-partners-with-cytostatic-proline-rich-polypeptide-1-in-human-chondrosarcoma
#9
Karina Galoian, Silva Abrahamyan, Gor Chailyan, Amir Qureshi, Parthik Patel, Gil Metser, Alexandra Moran, Inesa Sahakyan, Narine Tumasyan, Albert Lee, Tigran Davtyan, Samvel Chailyan, Armen Galoyan
Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma...
November 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29138336/correction-for-dixit-et-al-fuse-binding-protein-1-facilitates-persistent-hepatitis-c-virus-replication-in-hepatoma-cells-by-regulating-tumor-suppressor-p53
#10
Updesh Dixit, Ashutosh K Pandey, Zhihe Liu, Sushil Kumar, Matthew B Neiditch, Kenneth M Klein, Virendra N Pandey
No abstract text is available yet for this article.
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29138235/brip1-overexpression-is-correlated-with-clinical-features-and-survival-outcome-of-luminal-breast-cancer-subtypes
#11
Ishita Gupta, Allal Ouhtit, Adil Al-Ajmi, Syed Gauhar A Rizvi, Hamad Al-Riyami, Marwa Al-Riyami, Yahya Tamimi
In Oman, breast cancer is most common, representing approximately more than 25% of all cancers in women. Relatively younger populations of patients (25 to 40 years) present surprisingly with an aggressive phenotype and advanced tumor stages. In this study, we investigated differential gene expressions in Luminal-A, Luminal-B, Triple negative and Her2+ breast cancer subtypes and compared data to benign tumor samples. We identified a potential candidate gene BRIP1, showing differential expression in the four breast cancer subtypes examined, suggesting that BRIP1 has the profile of a useful diagnostic marker, suitable for targeted therapeutic intervention...
November 14, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29137437/dna-hypermethyation-and-silencing-of-pitx1-correlated-with-advanced-stage-and-poor-postoperative-prognosis-of-esophageal-squamous-cell-carcinoma
#12
Takeshi Otsubo, Kazuhiko Yamada, Teruki Hagiwara, Kenshiro Oshima, Kei Iida, Koro Nishikata, Tetsuro Toyoda, Toru Igari, Kyoko Nohara, Satoshi Yamashita, Masahira Hattori, Taeko Dohi, Yuki I Kawamura
Esophageal squamous cell carcinoma (ESCC) is associated with the accumulation of genetic and epigenetic changes in the background mucosa. Dysregulated DNA methylation is known to lead to the inactivation of tumor suppressor genes and the activation of oncogenes. To identify the genes whose expression is perturbed by abnormal DNA methylation in ESCC, integrative transcriptomics by serial analysis of gene expression (SAGE) and methylome sequencing by methyl-DNA immunoprecipitation (MeDIP) analysis were performed...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137428/pten-loss-is-associated-with-prostate-cancer-recurrence-and-alterations-in-tumor-dna-methylation-profiles
#13
Milan S Geybels, Min Fang, Jonathan L Wright, Xiaoyu Qu, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Ziding Feng, Elaine A Ostrander, Peter S Nelson, Janet L Stanford
Background: Prostate cancer (PCa) with loss of the tumor suppressor gene PTEN has an unfavorable prognosis. DNA methylation profiles associated with PTEN loss may provide further insights into the mechanisms underlying these more aggressive, clinically relevant tumors. Methods: The cohort included patients with clinically localized PCa. Samples taken from the primary tumor were used to determine PTEN genomic deletions using FISH, and to analyze epigenome-wide DNA methylation profiles...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137411/a-novel-polyamine-blockade-therapy-activates-an-anti-tumor-immune-response
#14
Eric T Alexander, Allyson Minton, Molly C Peters, Otto Phanstiel, Susan K Gilmour
Most tumors maintain elevated levels of polyamines to support their growth and survival. This study explores the anti-tumor effect of polyamine starvation via both inhibiting polyamine biosynthesis and blocking the upregulated import of polyamines into the tumor. We demonstrate that polyamine blockade therapy (PBT) co-treatment with both DFMO and a novel polyamine transport inhibitor, Trimer PTI, significantly inhibits tumor growth more than treatment with DFMO or the Trimer PTI alone. The anti-tumor effect of PBT was lost in mice where CD4(+) and CD8(+) T cells were antibody depleted, implying that PBT stimulates an anti-tumor immune effect that is T-cell dependent...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137392/selective-secretion-of-micrornas-from-lung-cancer-cells-via-extracellular-vesicles-promotes-camk1d-mediated-tube-formation-in-endothelial-cells
#15
James Lawson, Christopher Dickman, Sara MacLellan, Rebecca Towle, James Jabalee, Stephen Lam, Cathie Garnis
Extracellular vesicles (EVs) are key signaling mediators between cancer cells and their supporting stroma, and regulate critical processes such as invasion, metastases, and angiogenesis. We have identified a subset of miRNAs (miR-142-3p, miR-143-3p, miR-145-5p, miR-150-5p, miR-223-3p, miR-451a, miR-486-5p, miR-605-5p) that are enriched in lung adenocarcinoma extracellular vesicles compared to the donor cells from which they were derived. Two well-known tumor suppressors, miR-143-3p and miR-145-5p, were also enriched in serum samples collected during surgery from blood vessels draining directly from lung adenocarcinoma tumor beds...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137391/activated-spleen-tyrosine-kinase-promotes-malignant-progression-of-oral-squamous-cell-carcinoma-via-mtor-s6-signaling-pathway-in-an-erk1-2-independent-manner
#16
Pan Gao, Xianghe Qiao, Haibin Sun, Yi Huang, Jie Lin, Longjiang Li, Xiaoyi Wang, Chunjie Li
Spleen tyrosine kinase (SYK), a non-receptor cytoplasmic tyrosine enzyme, is well known for its ability in certain pathways through immune receptors. Recently, SYK role in cancer has been widely studied. SYK plays a dual role as a tumor suppressor and tumor promoter. Nevertheless, its role in oral squamous cell carcinoma (OSCC) has not been fully investigated. In the current study, samples from OSCC tumors and adjacent normal counterparts were collected and SYK expression was evaluated by real-time qPCR. SYK mRNA expression in tumors was higher than the normal tissues...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137372/microrna-33a-5p-increases-radiosensitivity-by-inhibiting-glycolysis-in-melanoma
#17
Ke Cao, Jingjing Li, Jia Chen, Li Qian, Aijun Wang, Xiang Chen, Wei Xiong, Jintian Tang, Shijie Tang, Yong Chen, Yao Chen, Yan Cheng, Jianda Zhou
Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137357/akr7a3-suppresses-tumorigenicity-and-chemoresistance-in-hepatocellular-carcinoma-through-attenuation-of-erk-c-jun-and-nf-%C3%AE%C2%BAb-signaling-pathways
#18
Raymond Kwok Kei Chow, Sarah Tsz-Kwan Sin, Ming Liu, Yan Li, Tim Hon Man Chan, Yangyang Song, Leilei Chen, Dora Lai-Wan Kwong, Xin-Yuan Guan
Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here we reported that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137356/disruption-of-stat3-dnmt1-interaction-by-sh-i-14-induces-re-expression-of-tumor-suppressor-genes-and-inhibits-growth-of-triple-negative-breast-tumor
#19
Hyo Jin Kang, Yong Weon Yi, Shu-Jie Hou, Hee Jeong Kim, Yali Kong, Insoo Bae, Milton L Brown
Epigenetic regulation of gene expression is an emerging target to treat several human diseases including cancers. In cancers, expressions of many tumor suppressor genes are suppressed by hyper-methylation in their regulatory regions. Herein, we describe a novel carbazole SH-I-14 that decreased the level of the acetyl-STAT3 at the K685 residue. Mutation analysis revealed that SH-I-14 disrupted STAT3-DNMT1 interaction by removing acetyl group from K685 of STAT3. Finally, the inhibition of STAT3-DNMT1 interaction by SH-I-14 resulted in re-expression of tumor suppressor genes such as VHL and PDLIM4 through de-methylation of their promoter regions...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137325/rlim-suppresses-hepatocellular-carcinogenesis-by-up-regulating-p15-and-p21
#20
Yongsheng Huang, Meng Nie, Chuang Li, Yingjie Zhao, Jiahui Li, Lan Zhou, Lin Wang
Hepatocellular carcinogenesis results from dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation and apoptosis. p15 and p21 are cyclin-dependent kinase inhibitors, which arrest cell proliferation and serve as critical tumor suppressors. Here we report that the E3 ubiquitin ligase RLIM expression is downregulated in hepatocellular carcinoma patients, and correlated with p15 and p21 expression in clinical progression. In addition, we showed that RLIM overexpression suppresses the cell growth and arrests cell cycle progression of hepatocellular carcinoma...
October 10, 2017: Oncotarget
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