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https://www.readbyqxmd.com/read/28646512/wmj-8-b-a-novel-hydroxamate-derivative-induces-mda-mb-231-breast-cancer-cell-death-via-shp-1-stat3-survivin-cascade
#1
Yu-Fan Chuang, Shiu-Wen Huang, Ya-Fen Hsu, Meng-Chieh Yu, George Ou, Wei-Jan Huang, Ming-Jen Hsu
BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors with broad-spectrum anti-tumor properties has been described and attracted lots of attention in the field of drug discovery. However, the underlying anti-tumor mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms of a novel hydroxamate-based HDAC inhibitor, WMJ-8-B, in inducing MDA-MB-231 breast cancer cell death. EXPERIMENTAL APPROACH: WMJ-8-B's effects on cell viability, cell cycle distribution, apoptosis, as well as signaling molecules modification and activation were analyzed by MTT assay, flowcytometric analysis, immunoblotting, reporter assay, ChIP analysis and siRNA strategy...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28637870/cardiac-myocyte-p38%C3%AE-kinase-regulates-angiogenesis-via-myocyte-endothelial-cell-cross-talk-during-stress-induced-remodeling-in-heart
#2
Beth A Rose, Tomohiro Yokota, Vishnu Chintalgattu, Shuxun Ren, Luisa Iruela-Arispe, Aarif Y Khakoo, Susumu Minamisawa, Yibin Wang
Stress-induced p38 mitogen-activated protein kinase (MAPK) activity is implicated in pathological remodeling in the heart. For example, constitutive p38 MAPK activation in cardiomyocytes induces pathological features, including myocyte hypertrophy, apoptosis, contractile dysfunction, and fetal gene expression. However, the physiological function of cardiomyocyte p38 MAPK activity in beneficial compensatory vascular remodeling is unclear. This report investigated the functional role and the underlying mechanisms of cardiomyocyte p38 MAPK activity in cardiac remodeling induced by chronic stress...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637794/a-trpv1-to-secretagogin-regulatory-axis-controls-pancreatic-%C3%AE-cell-survival-by-modulating-protein-turnover
#3
Katarzyna Malenczyk, Fatima Girach, Edit Szodorai, Petter Storm, Åsa Segerstolpe, Giuseppe Tortoriello, Robert Schnell, Jan Mulder, Roman A Romanov, Erzsébet Borók, Fabiana Piscitelli, Vincenzo Di Marzo, Gábor Szabó, Rickard Sandberg, Stefan Kubicek, Gert Lubec, Tomas Hökfelt, Ludwig Wagner, Leif Groop, Tibor Harkany
Ca(2+)-sensor proteins are generally implicated in insulin release through SNARE interactions. Here, secretagogin, whose expression in human pancreatic islets correlates with their insulin content and the incidence of type 2 diabetes, is shown to orchestrate an unexpectedly distinct mechanism. Single-cell RNA-seq reveals retained expression of the TRP family members in β-cells from diabetic donors. Amongst these, pharmacological probing identifies Ca(2+)-permeable transient receptor potential vanilloid type 1 channels (TRPV1) as potent inducers of secretagogin expression through recruitment of Sp1 transcription factors...
June 21, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28631560/mithramycin-inhibits-epithelial-to-mesenchymal-transition-and-invasion-by-downregulating-sp1-and-snai1-in-salivary-adenoid-cystic-carcinoma
#4
Jiasu Li, Hongmei Gao, Lingxu Meng, Lin Yin
Mithramycin exhibits certain anticancer effects in glioma, metastatic cerebral carcinoma, malignant lymphoma, chorionic carcinoma and breast cancer. However, its effects on salivary adenoid cystic carcinoma remain unclear. Here, we report that mithramycin significantly inhibited epithelial-to-mesenchymal transition and invasion in human salivary adenoid cystic carcinoma cell lines. The underlying mechanism for this activity was further demonstrated to involve decreasing the expression of the transcription factors specificity protein 1 and SNAI1...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28627662/microrna-363-3p-is-downregulated-in-hepatocellular-carcinoma-and-inhibits-tumorigenesis-by-directly-targeting-specificity-protein-1
#5
Jie Ying, Xuechun Yu, Chaojian Ma, Yongqi Zhang, Jingwu Dong
microRNAs exhibit important regulatory roles in tumorigenesis and tumor development, such as in hepatocellular carcinoma (HCC). The present study aimed to investigate the expression and functional roles of microRNA (miR)‑363‑3p in HCC. miR-363-3p expression levels in a number of HCC tissues and cell lines were measured by reverse transcription-quantitative PCR (RT‑qPCR). The effects of miR‑363‑3p expression on HCC cell proliferation, migration and invasion were exa-mined by MTT assay, Transwell migration and invasion assay, respectively...
June 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627594/microrna-320-inhibits-cell-proliferation-migration-and-invasion-in-retinoblastoma-by-targeting-specificity-protein-1
#6
Yuehua Zhao, Shilian Zhang, Yongfeng Zhang
Research into the expression and function of microRNAs (miRNAs/miR) in human cancer has provided novel insights into the molecular mechanisms underlying carcinogenesis and cancer progression. Aberrant miRNA expression has been reported in retinoblastoma (RB) and several other types of human cancer. The present study demonstrated that miR‑320 is significantly downregulated in RB tissues and cell lines. Furthermore, overexpression of miR‑320 was demonstrated to inhibit proliferation, migration and invasion of RB cells...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627437/molecular-characterization-and-functional-analysis-of-ppar%C3%AE-promoter-in-yellow-catfish-pelteobagrus-fulvidraco
#7
Wen-Jing You, Yao-Fang Fan, Yi-Huan Xu, Kun Wu, Xiao-Ying Tan
Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that plays critical roles in the regulation of many important physiological processes. In the present study, the 1686-bp PPARα promoter for yellow catfish Pelteobagrus fulvidraco was first cloned and characterized. The transcription start site (TSS) of PPARα gene was mapped using RLM-5'RACE method. The luciferase vectors were constructed and transiently transfected into HepG2 cells and HEK293 cells, respectively, for functional analysis of promoters...
June 13, 2017: Gene
https://www.readbyqxmd.com/read/28624189/mir30c-is-involved-in-diabetic-cardiomyopathy-through-regulation-of-cardiac-autophagy-via-becn1
#8
Chen Chen, Shenglan Yang, Huaping Li, Zhongwei Yin, Jiahui Fan, Yanru Zhao, Wei Gong, Mengwen Yan, Dao Wen Wang
Multiple factors have been shown to promote the progression of diabetic cardiomyopathy. A link has previously been found between Mir30 and autophagy in cancer cells and in the heart, but the role of Mir30 in diabetic heart has not been studied. Using in vitro and in vivo approaches, we found that the depletion of Mir30c and induction of BECN1 enhanced autophagy in diabetic (db/db) hearts and in cardiomyocytes treated with the fatty acid palmitate. We verified that Mir30c repressed BECN1 expression by direct binding to the BECN1 3' UTRs...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623294/h2s-and-homocysteine-control-a-novel-feedback-regulation-of-cystathionine-beta-synthase-and-cystathionine-gamma-lyase-in-cardiomyocytes
#9
Shyam Sundar Nandi, Paras Kumar Mishra
Hydrogen sulfide (H2S), a cardioprotective gas, is endogenously produced from homocysteine by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE) enzymes. However, effect of H2S or homocysteine on CBS and CSE expression, and cross-talk between CBS and CSE are unclear. We hypothesize that homocysteine and H2S regulate CBS and CSE expressions in a dose dependent manner in cardiomyocytes, and CBS deficiency induces cardiac CSE expression. To test the hypothesis, we treated murine atrial HL1 cardiomyocytes with increasing doses of homocysteine or Na2S/GYY4137, a H2S donor, and measured the levels of CBS and CSE...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623129/increased-expression-of-microrna-31-5p-inhibits-cell-proliferation-migration-and-invasion-via-regulating-sp1-transcription-factor-in-hepg2-hepatocellular-carcinoma-cell-line
#10
Guoliang Zhao, Chuangye Han, Zhi Zhang, Lei Wang, Jing Xu
Accumulating evidence has suggested that microRNA-31-5p (miR-31-5p) is dysfunctional in hepatocellular carcinoma (HCC). However, the molecular mechanism of HCC remains unclear. In this study, we investigated the role of miR-31-5p in tumor formation and development of HCC. The expression of miR-31-5p was detected in HCC tissues, corresponding adjacent tissues, normal liver tissues, and HCC cell lines. miR-31-5p mimics and an inhibitor were transfected into HepG2 cells to assess the effects of miR-31-5p on cell proliferation, apoptosis, cell cycle, migration, and invasion assays...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28615712/cell-specific-expression-of-aquaporin-5-aqp5-in-alveolar-epithelium-is-directed-by-gata6-sp1-via-histone-acetylation
#11
Per Flodby, Changgong Li, Yixin Liu, Hongjun Wang, Megan E Rieger, Parviz Minoo, Edward D Crandall, David K Ann, Zea Borok, Beiyun Zhou
Epigenetic regulation of differentiation-related genes is poorly understood. We previously reported that transcription factors GATA6 and Sp1 interact with and activate the rat proximal 358-bp promoter/enhancer (p358P/E) of lung alveolar epithelial type I (AT1) cell-specific gene aquaporin-5 (Aqp5). In this study, we found that histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) increased AQP5 expression and Sp1-mediated transcription of p358P/E. HDAC3 overexpression inhibited Sp1-mediated Aqp5 activation, while HDAC3 knockdown augmented AQP5 protein expression...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610841/hsp27-promotes-abca1-expression-and-cholesterol-efflux-through-the-pi3k-pkc%C3%AE-sp1-pathway-in-thp-1-macrophages
#12
Hai-Jun Kuang, Guo-Jun Zhao, Wu-Jun Chen, Min Zhang, Gao-Feng Zeng, Xi-Long Zheng, Chao-Ke Tang
Heat shock protein 27 (Hsp27) is a putative biomarker and therapeutic target in atherosclerosis. This study was to explore the potential mechanisms underlying Hsp27 effects on ATP-binding cassette transporter A1 (ABCA1) expression and cellular cholesterol efflux. THP-1 macrophage-derived foam cells were infected with adenovirus to express wild-type Hsp27, hyper-phosphorylated Hsp27 mimic (3D Hsp27), antisense Hsp27 or hypo-phosphorylated Hsp27 mimic (3A Hsp27). Wild-type and 3D Hsp27 were found to up-regulate ABCA1 mRNA and protein expression and increase cholesterol efflux from cells...
June 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28607147/loss-of-the-clock-protein-per2-shortens-the-erythrocyte-life-span-in-mice
#13
Qi Sun, Yue Zhao, Yunxia Yang, Xiao Yang, Minghui Li, Xi Xu, Dan Weng, Junsong Wang, Jianfa Zhang
Cell proliferation and release from the bone marrow have been demonstrated to be controlled by circadian rhythms in both humans and mice. However, it is unclear whether local circadian clocks in the bone marrow influence physiological functions and life span of erythrocytes. Here, we report that loss of the clock gene Per2 significantly decreased erythrocyte life span. Mice deficient in Per2 were more susceptible to acute stresses in the erythrocytes, becoming severely anemic upon phenylhydrazine, osmotic, and H2O2 challenges...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28596967/prdx6-upregulation-by-curcumin-attenuates-ischemic-oxidative-damage-via-sp1-in-rats-after-stroke
#14
Gongwei Jia, Botao Tan, Jingxi Ma, Lina Zhang, Xinhao Jin, Changqing Li
BACKGROUND: The role of Peroxiredoxin 6 (Prdx6) in brain ischemia remains unclear. Curcumin (Cur) treatment elicits neuroprotective effects against cerebral ischemic injury, and the associated mechanisms may involve Prdx6. In this study, we investigated whether Prdx6 and the transcription factor specific protein 1 (SP1) were involved in the antioxidant effect of Cur after stoke. METHODS: Focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 2 hours in male Sprague-Dawley rats treated with or without Prdx6 siRNA...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28587787/importance-of-n-and-c-terminal-residues-of-substance-p-1-7-for-alleviating-allodynia-in-mice-after-peripheral-administration
#15
Anna Skogh, Anna Lesniak, Fabienne Z Gaugaz, Richard Svensson, Gunnar Lindeberg, Rebecca Fransson, Fred Nyberg, Mathias Hallberg, Anja Sandström
The heptapeptide SP1-7 (1, Arg(1)-Pro(2)-Lys(3)-Pro(4)-Gln(5)-Gln(6)-Phe(7)) is the major bioactive metabolite formed after proteolytic processing of the neuropeptide substance P (SP, Arg(1)-Pro(2)-Lys(3)-Pro(4)-Gln(5)-Gln(6)-Phe(7)-Phe(8)-Gly(9)-Leu(10)-Met(11)-NH2). The heptapeptide 1 frequently exhibits opposite effects to those induced by SP, such as exerting antinociception, or attenuating thermal hyperalgesia and mechanical allodynia. The heptapeptide SP1-7 amide (2, Arg(1)-Pro(2)-Lys(3)-Pro(4)-Gln(5)-Gln(6)-Phe(7)-NH2) is often more efficacious than 1 in experimental pain models...
June 3, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28586012/methylated-322-327-cpg-site-decreases-hogg1-mrna-expression-in-non-small-cell-lung-cancer
#16
Yuanyuan Zeng, Jianjie Zhu, Hualong Qin, Dan Shen, Zhe Lei, Wei Li, Zongli Ding, Jian-An Huang, Zeyi Liu
hOGG1 plays a role in several disease pathways, including various cancers. Despite such functional importance, how hOGG1 is regulated at the transcriptional level in human non-small cell lung cancer (NSCLC) remains unknown, particularly via DNA methylation changes. We obtained NSCLC tissues and adjacent non-cancerous tissues and examined hOGG1 mRNA expression levels. NSCLC cells were treated with 5-Aza to test whether DNA methylation can influence the expression of hOGG1. The MassARRAY EpiTYPER and luciferase reporter gene assays were used to define the functional region of the hOGG1 gene (including CpG sites)...
June 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28574228/apkc-%C3%AE-p-sp1-snail-signaling-induces-epithelial-mesenchymal-transition-and-immunosuppression-in-cholangiocarcinoma
#17
Yawei Qian, Wei Yao, Tao Yang, Yan Yang, Yan Liu, Qi Shen, Jian Zhang, Weipeng Qi, Jianming Wang
Cholangiocarcinoma (CCA) is a highly malignant bile duct cancer that tends to invade and metastasize early. The epithelial-mesenchymal transition (EMT) has been implicated in cancer cell invasion and metastasis, as well as in cancer cell evasion of host immunity. In this study, we investigated the interaction between atypical protein kinase C-iota (aPKC-ι) and Snail in the regulation of EMT and its relationship to CCA immunosuppression. Our results demonstrated that aPKC-ι, Snail, and infiltrated immunosuppressive cells were significantly up-regulated in CCA tumor tissues and were linked to poor prognosis...
June 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28572574/survive-or-thrive-tradeoff-strategy-for-cellular-senescence
#18
REVIEW
Sang Chul Park
Aging-dependent cellular behaviors toward extrinsic stress are characterized by the confined localization of certain molecules to either nuclear or perinuclear regions. Although most growth factors can activate downstream signaling in aging cells, they do not in fact have any impact on the cells because the signals cannot reach their genetic targets in the nucleus. For the same reason, varying apoptotic stress factors cannot stimulate the apoptotic pathway in senescent cells. Thus, the operation of a functional nuclear barrier in an aging-dependent manner has been investigated...
June 2, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28570591/statin-and-rottlerin-small-molecule-inhibitors-restrict-colon-cancer-progression-and-metastasis-via-macc1
#19
Manisha Juneja, Dennis Kobelt, Wolfgang Walther, Cynthia Voss, Janice Smith, Edgar Specker, Martin Neuenschwander, Björn-Oliver Gohlke, Mathias Dahlmann, Silke Radetzki, Robert Preissner, Jens Peter von Kries, Peter Michael Schlag, Ulrike Stein
MACC1 (Metastasis Associated in Colon Cancer 1) is a key driver and prognostic biomarker for cancer progression and metastasis in a large variety of solid tumor types, particularly colorectal cancer (CRC). However, no MACC1 inhibitors have been identified yet. Therefore, we aimed to target MACC1 expression using a luciferase reporter-based high-throughput screening with the ChemBioNet library of more than 30,000 compounds. The small molecules lovastatin and rottlerin emerged as the most potent MACC1 transcriptional inhibitors...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28569779/long-noncoding-rna-uca1-induced-by-sp1-promotes-cell-proliferation-via-recruiting-ezh2-and-activating-akt-pathway-in-gastric-cancer
#20
Zhen-Qiang Wang, Qiang Cai, Lei Hu, Chang-Yu He, Jian-Fang Li, Zhi-Wei Quan, Bing-Ya Liu, Chen Li, Zheng-Gang Zhu
Long noncoding RNA UCA1 has emerged as a novel regulator in cancer initiation and progression of various cancers. However, function and underlying mechanism of UCA1 in the progression of gastric cancer (GC) remain unclear. In the present study, we report that UCA1 expressed highly in GC tissues and GC cells, which was partly induced by SP1. UCA1 promoted GC cell proliferation and G1/S transition in vitro and in vivo. Moreover, UCA1 exerted its function through interacting with EZH2, promoting direct interaction with cyclin D1 promoter to activate the translation of cyclin D1...
June 1, 2017: Cell Death & Disease
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