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https://www.readbyqxmd.com/read/29165358/understanding-the-molecular-genetics-of-basal-cell-carcinoma
#1
REVIEW
Cristina Pellegrini, Maria Giovanna Maturo, Lucia Di Nardo, Valeria Ciciarelli, Carlota Gutiérrez García-Rodrigo, Maria Concetta Fargnoli
Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29165337/mirnome-profiling-in-bicuspid-aortic-valve-associated-aortopathy-by-next-generation-sequencing
#2
Andrea Borghini, Ilenia Foffa, Silvia Pulignani, Cecilia Vecoli, Lamia Ait-Ali, Maria Grazia Andreassi
The molecular mechanisms underlying thoracic aortic aneurysm (TAA) in patients with bicuspid aortic valve (BAV) are incompletely characterized. MicroRNAs (miRNAs) may play a major role in the different pathogenesis of aortopathy. We sought to employ next-generation sequencing to analyze the entire miRNome in TAA tissue from patients with BAV and tricuspid aortic valve (TAV). In the discovery stage, small RNA sequencing was performed using the Illumina MiSeq platform in 13 TAA tissue samples (seven patients with BAV and six with TAV)...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29162747/therapeutic-effect-of-a-novel-wnt-pathway-inhibitor-on-cardiac-regeneration-after-myocardial-infarction
#3
Chunyu Zeng, Dezhong Yang, Wenbin Fu, Liangpeng Li, Xuewei Xia, Qiao Liao, Rongchuan Yue, Hongmei Chen, Xiongwen Chen, Songzhu An, Wei Eric Wang
After myocardial infarction (MI), the heart is difficult to repair because of great loss of cardiomyoctyes and lack of cardiac regeneration. Novel drug candidates that aim at reducing pathological remodeling and stimulating cardiac regeneration are highly desirable. In this study, we identified if and how a novel porcupine inhibitor CGX1321 influenced MI and cardiac regeneration. Permanent ligation of left anterior descending (LAD) coronary artery was performed in mice to induce MI injury. Cardiac function was measured by echocardiography, infarct size was examined by TTC staining...
November 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29158053/transforming-growth-factor-beta1-promotes-articular-cartilage-repair-through-canonical-smad-and-hippo-pathways-in-bone-mesenchymal-stem-cells
#4
Jun Ying, Pinger Wang, Shanxing Zhang, Taotao Xu, Lei Zhang, Rui Dong, Shibing Xu, Peijian Tong, Chengliang Wu, Hongting Jin
AIMS: Transforming growth factor-β1 (TGF-β1) is a chondrogenic factor and has been reported to be able to enhance chondrocyte differentiation from bone marrow mesenchymal stem cells (BMSCs). Here we investigate the molecular mechanism through which TGF-β1 chronically promotes the repair of cartilage defect and inhibit chondrocyte hypertrophy. MAIN METHODS: Animal models of full thickness cartilage defects were divided into three groups: model group, BMSCs group (treated with BMSCs/calcium alginate gel) and BMSCs+TGF-β1 group (treated with Lentivirus-TGF-β1-EGFP transduced BMSCs/calcium alginate gel)...
November 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29157094/tead4-promotes-colorectal-tumorigenesis-via-transcriptionally-targeting-yap1
#5
Jia-Yin Tang, Chen-Yang Yu, Yu-Jie Bao, Lu Chen, Jinxian Chen, Sheng-Li Yang, Hao-Yan Chen, Jie Hong, Jing-Yuan Fang
TEAD4 (TEA domain family member 4) was recently revealed as an oncogenic character in tumorigenesis. However, its role remains unclear in colorectal tumorigenesis. Here, we firstly found that the expression level of TEAD4 was significantly elevated in clinical samples of colorectal adenomas (CRA) and correlated with the size and histological type of CRA. Moreover, patients with higher TEAD4 expression in normal colon mucosa are more prone to be recurrent after polypectomy. TEAD4 knockdown significantly inhibited colorectal cell proliferation in vitro and suppressed tumor growth in vivo...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156814/screening-circular-rna-expression-patterns-following-focal-cerebral-ischemia-in-mice
#6
Cuiying Liu, Chencheng Zhang, Jian Yang, Xiaokun Geng, Huishan Du, Xunming Ji, Heng Zhao
Circular RNAs (circRNAs) have been demonstrated to act as microRNA (miRNA) sponges and they play important roles in regulating gene expression through a circRNA-miRNA-gene pathway. The specific roles of circRNAs in the pathogenesis of cerebral ischemia, however, are still unclear. Thus, the aim of this study is to determine circRNA expression profiles in the ischemic brain after stroke, which was induced by 45 min of transient middle cerebral artery occlusion (MCAO). The results from the circRNA microarrays revealed that 1027 circRNAs were significantly altered 48 hours after reperfusion in the ischemic brain compared with the sham group...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156422/syndecan-1-in-mechanosensing-of-nanotopological-cues-in-engineered-materials
#7
Victoria Le, Jason Lee, Somali Chaterji, Adrianne Spencer, Yen-Liang Liu, Peter Kim, Hsin-Chih Yeh, Deok-Ho Kim, Aaron B Baker
The cells of the vascular system are highly sensitive to biophysical cues from their local cellular microenvironment. To engineer improved materials for vascular devices and delivery of cell therapies, a key challenge is to understand the mechanisms that cells use to sense biophysical cues from their environment. Syndecans are heparan sulfate proteoglycans (HSPGs) that consist of a protein core modified with heparan sulfate glycosaminoglycan chains. Due to their presence on the cell surface and their interaction with cytoskeletal and focal adhesion associated molecules, cell surface proteoglycans are well poised to serve as mechanosensors of the cellular microenvironment...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29155585/allosteric-inhibitors-of-shp2-with-therapeutic-potential-for-cancer-treatment
#8
Jingjing Xie, Xiaojia Si, Shoulai Gu, Mingliang Wang, Jian Shen, Haoyan Li, Jian Shen, Dan Li, Yanjia Fang, Cong Liu, Jidong Zhu
SHP2, a cytoplasmic protein-tyrosine phosphatase encoded by the PTPN11 gene, is involved in multiple cell signaling processes including Ras/MAPK and Hippo/YAP pathways. SHP2 has been shown to contribute to the progression of a number of cancer types including leukemia, gastric and breast cancer. It also regulates T-cell activation by interacting with inhibitory immune checkpoint receptors such as the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA). Thus, SHP2 inhibitors have drawn great attention by both inhibiting tumor cell proliferation and activating T cell immune responses toward cancer cells...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155025/understanding-the-role-of-mammalian-sterile-20-like-kinase-1-mst1-in-cardiovascular-disorders
#9
REVIEW
Yang Yang, Haichang Wang, Zhiqiang Ma, Wei Hu, Dongdong Sun
Hippo signaling is a conserved pathway and plays important role in controlling cell proliferation and differentiation. As critical components of the Hippo pathway in mammals, mammalian sterile 20-like kinase 1 (MST1) participate in cell apoptosis and cell proliferation. Yes-associated protein (YAP) acts as a downstream transcriptional co-activator of MST1. MST1 is present in heart tissue and helps determine the fate of cardiomyocytes by regulating the balance between autophagy and apoptosis. Recent studies showed MST1 signaling is an essential participant in many cardiovascular disorders, including aortic dissection, aortic aneurysm, atherosclerosis, myocardial ischemic injury, and cardiomyopathy...
November 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29154888/activation-of-yap1-taz-signaling-in-ischemic-heart-disease-and-dilated-cardiomyopathy
#10
Ning Hou, Ying Wen, Xun Yuan, Haodong Xu, Xuejun Wang, Faqian Li, Bo Ye
Genetic manipulation of key components of the evolutionally conserved Hippo pathway has shown that the precise control of these signaling molecules is critical to cardiac development and response to stresses. However, how this pathway is involved in the progression of cardiac dysfunction in different heart diseases remains unclear. We investigated the expressional levels and subcellular localization of Yap1, Taz, and Tead1 and determined Hippo target gene expression in failing human hearts with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (IDC) and mouse desmin-related cardiomyopathy (DES)...
November 15, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29154163/upstairs-downstairs-spatial-regulation-of-hippo-signalling
#11
REVIEW
Alexander Fulford, Nicolas Tapon, Paulo S Ribeiro
Cellular signalling lies at the heart of every decision involved in the development and homeostasis of multicellular organisms. The Hippo pathway was discovered nearly two decades ago through seminal work in Drosophila and rapidly emerged as a crucial signalling network implicated in developmental and oncogenic growth, tissue regeneration and stem cell biology. Here, we review recent advances in the field relating to the upstream regulation of Hippo signalling and the intracellular tug-of-war that tightly controls its main target, the transcriptional co-activator Yorkie/YAP...
November 16, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#12
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29145896/downregulation-of-mir-31-stimulates-expression-of-lats2-via-the-hippo-pathway-and-promotes-epithelial-mesenchymal-transition-in-esophageal-squamous-cell-carcinoma
#13
Yanping Gao, Jun Yi, Kai Zhang, Fan Bai, Bing Feng, Rui Wang, Xiaoyuan Chu, Longbang Chen, Haizhu Song
BACKGROUND: Dysregulation of miRNAs is associated with cancer development by coordinately suppressing abundant target genes. Emerging evidence indicates that miR-31 plays a dual role in tumorigenicity. However, whether miR-31 plays as an oncogene in esophageal squamous cell carcinoma (ESCC) and the potential target molecules are still unclear. MiR-31 role in ESCC was investigated and an association of the target molecules with EMT was identified in the progression of ESCC. METHODS: Western blot assays and qRT-PCR was performed to detect the protein and mRNA levels...
November 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29142959/hemodialysis-infection-prevention-protocols-ontario-shower-technique-hippo-st-a-pilot-randomized-trial
#14
S Daisy Kosa, Amiram Gafni, Andrew A House, JulieAnn Lawrence, Louise Moist, Bharat Nathoo, Paul Tam, Alicia Sarabia, Lehana Thabane, George Wu, Charmaine E Lok
Introduction: We developed the Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST) to permit hemodialysis (HD) patients with central venous catheters (catheters) to shower without additional infection risk. Our primary objective was to determine the feasibility of conducting a parallel randomized controlled trial (RCT) to evaluate the impact of HIPPO-ST on catheter-related bacteremia (CRB) in adult HD patients. Methods: Adult HD patients using catheters were recruited from 11 HD units...
March 2017: KI Reports
https://www.readbyqxmd.com/read/29136529/yap-dependent-axl-overexpression-mediates-resistance-to-egfr-inhibitors-in-nsclc
#15
Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer...
November 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29133764/advanced-role-of-hippo-signaling-in-endometrial-fibrosis-implications-for-intrauterine-adhesion
#16
REVIEW
Hai-Yan Zhu, Tian-Xiang Ge, Yi-Bin Pan, Song-Ying Zhang
OBJECTIVE: Intrauterine adhesion (IUA) is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-β (TGF-β) signaling pathways to form an intricate network governing the development of fibrosis...
November 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29131252/yap1-up-regulation-inhibits-apoptosis-of-aortic-dissection-vascular-smooth-muscle-cells
#17
T Liu, J Xu, J-L Guo, C-Y Lin, W-M Luo, Y Yuan, H Liu, J Zhang
OBJECTIVE: Elevated apoptosis of vascular smooth muscle cell (VSMC) is correlated with the occurrence of aortic dissection (AD). Yes-associated protein 1 (YAP1) is the major effector in Hippo-YAP signal pathway, which facilitates cell proliferation and suppressing apoptosis. Several studies have been performed regarding the relationship between YAP1 and AD pathogenesis. This study established the AD rat model to investigate possible roles of YAP1 in regulating VSMC apoptosis and AD pathogenesis...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29130106/molecular-alterations-of-the-nf2-gene-in-hepatocellular-carcinoma-and-intrahepatic-cholangiocarcinoma
#18
Ning Zhang, Zhang Zhao, Jiang Long, Hai Li, Bei Zhang, Guangyong Chen, Xiaojin Li, Tingxia Lv, Wei Zhang, Xiaojuan Ou, Anjian Xu, Jian Huang
Neurofibromatosis type 2 with mutations in the neurofibromin 2 (NF2) gene, encoding the Merlin protein, is an autosomal dominant disorder characterized by enhanced cancer predisposition, particularly tumors of the central nervous system. Recent animal studies indicate that disruption of NF2/Merlin function in oval cells, which are hepatic progenitor cells, may lead to the development of primary liver cancers including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); however, its role in human primary liver cancer remains unclear...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29129684/rhoa-gtpase-controls-yap-mediated-ereg-signaling-in-small-intestinal-stem-cell-maintenance
#19
Ming Liu, Zheng Zhang, Leesa Sampson, Xuan Zhou, Kodandaramireddy Nalapareddy, Yuxin Feng, Shailaja Akunuru, Jaime Melendez, Ashley Kuenzi Davis, Feng Bi, Hartmut Geiger, Mei Xin, Yi Zheng
RHOA, a founding member of the Rho GTPase family, is critical for actomyosin dynamics, polarity, and morphogenesis in response to developmental cues, mechanical stress, and inflammation. In murine small intestinal epithelium, inducible RHOA deletion causes a loss of epithelial polarity, with disrupted villi and crypt organization. In the intestinal crypts, RHOA deficiency results in reduced cell proliferation, increased apoptosis, and a loss of intestinal stem cells (ISCs) that mimic effects of radiation damage...
November 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29126926/ajuba-increases-the-cisplatin-resistance-through-hippo-pathway-in-cervical-cancer
#20
Lihong Bi, Feng Ma, Rui Tian, Yanli Zhou, Weiguang Lan, Quanmao Song, Xiankui Cheng
Though LIM-domain protein AJUBA was identified as a putative oncogene, the function and underlying mechanisms of AJUBA in cervical cancer remain largely unknown. Firstly, AJUBA expression was detected via real-time quantitative PCR in patients' samples. Furthermore, Hela and Siha cells were transfected with AJUBA-overexpressing plasmids, and then exposed to cisplatin, the apoptosis was measured by cytometry assay. In addition, the expression of YAP and TAZ was disclosed through western blot assay. Our results revealed that AJUBA expression was significantly higher in the cervical cancer patients resistant to cisplatin treatment compared with cervical cancer patients sensitive to cisplatin treatment...
November 7, 2017: Gene
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