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Wnt activators

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https://www.readbyqxmd.com/read/28636101/knockdown-of-lncrna-meg3-inhibits-viability-migration-and-invasion-and-promotes-apoptosis-by-sponging-mir-127-in-osteosarcoma-cell
#1
Yang Wang, Daliang Kong
Osteosarcoma (OS) is one of the most common bone malignancies and occurs almost exclusively in children and adolescents. This study aimed to explore the role of lncRNA maternally expressed gene 3 (MEG3) in OS cells growth and metastasis, and to uncover the possible underlying mechanism. In this study, the expressions of MEG3 in five OS cell lines (MG63, OS-732, SaOS, G292, and 143B) and in a human osteoblast cell line hFOB1.19 were measured by qRT-PCR analysis. The expressions of MEG3, miR-127 and ZEB1 in OS-732 cells were overexpressed or suppressed by transfection...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28635355/aberrant-wnt-signaling-a-special-focus-in-cns-diseases
#2
Mercedes Arnés, Sergio Casas Tintó
Wnt signals regulate cell proliferation, migration and differentiation during development, as well as synaptic transmission and plasticity in the adult brain. Abnormal Wnt signaling is central to a number of brain pathologies. We review here, the significance of this pathway focused in the contribution of the most frequent alterations in receptors, secretable modulators and downstream targets in Alzheimer's disease (AD) and Glioblastoma (GBM). β-catenin and GSK3 levels are pivotal in the neurodegeneration associated to AD contributing to memory deficits, tau phosphorylation, increased β-amyloid production and modulation of Apolipoprotein E in the brain...
June 21, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28633632/antagonizing-mir-455-3p-inhibits-chemoresistance-and-aggressiveness-in-esophageal-squamous-cell-carcinoma
#3
Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
BACKGROUND: The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. METHODS: A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness...
June 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28631286/knockdown-of-mediator-subunit-med19-suppresses-bladder-cancer-cell-proliferation-and-migration-by-downregulating-wnt-%C3%AE-catenin-signalling-pathway
#4
Hejia Yuan, Shengqiang Yu, Yuanshan Cui, Changping Men, Diandong Yang, Zhenli Gao, Zhe Zhu, Jitao Wu
Mediator complex subunit 19 (Med19), a RNA polymerase II-embedded coactivator, is reported to be involved in bladder cancer (BCa) progression, but its functional contribution to this process is poorly understood. Here, we investigate the effects of Med19 on malignant behaviours of BCa, as well as to elucidate the possible mechanisms. Med19 expression in 15 BCa tissues was significantly higher than adjacent paired normal tissues using real-time PCR and Western blot analysis. Immunohistochemical staining of 167 paraffin-embedded BCa tissues was performed, and the results showed that high Med19 protein level was positively correlated with clinical stages and histopathological grade...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28630526/discriminating-value-of-calprotectin-in-disease-activity-and-progression-of-nonradiographic-axial-spondyloarthritis-and-ankylosing-spondylitis
#5
Jinxian Huang, Zhihua Yin, Guoxiang Song, Shengjin Cui, Jinzhao Jiang, Lijun Zhang
It has been controversial whether ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) are separate or different phases of radiographic progression. We determined that serum calprotectin level (ng/ml) was higher in AS (15.30 ± 6.49) and nr-axSpA (17.76 ± 8.59) patients than in healthy individuals (7.40 ± 2.67). No difference was observed in calprotectin level between these two groups. Elevated calprotectin was positively correlated with ESR, CRP, BASDAI, and ASDAS as well as SPARCC scoring and had no correlation with BASFI and mSASSS...
2017: Disease Markers
https://www.readbyqxmd.com/read/28630004/co-releasing-molecules-2-attenuates-ox-ldl-induced-injury-in-huvecs-by-ameliorating-mitochondrial-function-and-inhibiting-wnt-%C3%AE-catenin-pathway
#6
Hai-Jian Sun, Dong-Yan Xu, Yi-Xin Sun, Tong Xue, Chen-Xing Zhang, Zhi-Xuan Zhang, Wei Lin, Ke-Xue Li
Oxidized low-density lipoprotein (ox-LDL) is well known to disrupt normal functionality of endothelium, which plays a prominent role in endothelial dysfunction in many cardiovascular diseases. CO-releasing molecule 2 (CORM-2) is a promising candidate for treatment of cardiovascular diseases. However, it has not been defined whether CORM-2 might improve endothelial injury induced by ox-LDL. The present study was undertaken to determine the regulatory role of CORM-2 in cell injury of ox-LDL-treated human umbilical vein endothelial cells (HUVECs)...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629629/association-between-lithium-use-and-melanoma-risk-and-mortality-a-population-based-study
#7
Maryam M Asgari, Andy J Chien, Ai Lin Tsai, Bruce Fireman, Charles P Quesenberry
Laboratory studies show lithium, an activator of the Wnt/ß-catenin signaling pathway, slows melanoma progression, but no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk. Lithium exposure (n=11,317) was assessed from pharmacy databases, serum lithium levels were obtained from electronic laboratory databases, and incident cutaneous melanomas (n= 14,056) were identified from an established cancer registry...
June 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28629266/polygonatum-sibiricum-polysaccharide-promotes-osteoblastic-differentiation-through-the-erk-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway-in-vitro
#8
Xiaoming Peng, Jichen He, Jinmin Zhao, Yunle Wu, Xiongzhi Shi, Li Du, Mengni Nong, Shaohui Zong, Gao-Feng Zeng
Natural compound Polygonatum sibiricum polysaccharide (PSP) has a variety of biological actions such as reducing blood fat, antitumor, antioxidant activities, and enhancing immune function. In our previous study has revealed that PSP can promote osteoblastic differentiation in bone mesenchymal stem cells (BMSCs) by increasing nuclear accumulation of β-catenin. This study was designed to investigate that PSP can upregulate nuclear β-catenin, which was prevented by inhibiting glycogen synthase kinase 3β (GSK-3β) activity, by effectively activating Wnt signaling independent of low-density lipoprotein receptor-related protein (LRP5) ...
June 19, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28628975/highly-expressed-long-non-coding-rna-nnt-as1-promotes-cell-proliferation-and-invasion-through-wnt-%C3%AE-catenin-signaling-pathway-in-cervical-cancer
#9
Fangfang Hua, Shanshan Liu, Lihong Zhu, Ning Ma, Shan Jiang, Jun Yang
BACKGROUND: Cervical cancer is the most common gynecological malignancies in women worldwide. The previous study showed that lncRNA NNT-AS1 could play an important role in tumor development and metastasis of colorectal cancer. However, little is known about the function of NNT-AS1 in cervical cancer. The aim of this study was to investigate the expression profile of NNT-AS1 in cervical cancer and assess its possible molecular mechanism. METHODS: Relative expression levels of NNT-AS1 in cervical cancer tissues were determined by qRT-PCR...
June 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28628652/microrna-433-3p-promotes-osteoblast-differentiation-through-targeting-dkk1-expression
#10
Xiaolin Tang, Jiantao Lin, Guanhai Wang, Jianlin Lu
Dickkopf-1 (DKK1) is a powerful antagonist of canonical WNT signaling pathway, and is regarded as a biomarker for osteoporosis. Its expression is highly correlated with bone mass and osteoblasts maturation. In this study, mouse primary bone marrow cells and osteoblast cell lines were used. Luciferase reporter assay and western blotting methods were employed to validate if miRNA-433-3p epigenetically regulated DKK1 translation. Rat bone marrow derived osteoblasts were infected with lentivirus vector in which miR-433-3p was constructed...
2017: PloS One
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#11
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28628032/osteocyte-specific-wnt1-regulates-osteoblast-function-during-bone-homeostasis
#12
Kyu Sang Joeng, Yi-Chien Lee, Joohyun Lim, Yuqing Chen, Ming-Ming Jiang, Elda Munivez, Catherine Ambrose, Brendan H Lee
Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with spontaneous fractures similar to that observed in OI patients. Conversely, Wnt1 overexpression from osteocytes stimulated bone formation by increasing osteoblast number and activity, which was due in part to activation of mTORC1 signaling...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627774/decreased-expression-of-wnt2-in-villi-of-unexplained-recurrent-spontaneous-abortion-patients-may-cause-trophoblast-cell-dysfunction-via-downregulated-wnt-%C3%AE-catenin-signaling-pathway
#13
Ning Li, Shuhong Li, Yanwei Wang, Jiahui Wang, Kai Wang, Xin Liu, Yan Li, Juan Liu
WNT2 has been reported to be important for placental development, especially for the proper vascularization of the placenta. However, its precise role in first-trimester trophoblast cells is still unknown. WNT2 expression in the villous tissues of unexplained recurrent spontaneous abortion (URSA) patients was compared with that of healthy women by Western blot. The function of WNT2 in HTR-8/SVneo trophoblast cells was evaluated by altering the cellular WNT2 level through overexpression and shRNA knockdown. The molecular mechanism of the effect of WNT2 on trophoblast cells was investigated...
June 19, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28627706/the-wnt-inhibitor-lgk-974-enhances-radiosensitivity-of-hepg2-cells-by-modulating-nrf2-signaling
#14
Dan Tian, Ying Shi, Dexi Chen, Qiang Liu, Feiyue Fan
Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a master regulator of antioxidant and detoxification activities that can eliminate reactive oxygen species (ROS) produced via irradiation. However, Nrf2 overexpression in liver cancer cells may cause both radioresistance and chemoresistance. Reducing Nrf2 levels can enhance the radiosensitivity of HepG2 cells. Wingless/int-3A (Wnt3A) is a Wnt family protein that mainly activates the canonical Wnt signaling pathway. Recent studies showed that the Axin1-GSK-3β protein complex, a component of the canonical Wnt signaling pathway, can capture Nrf2 and facilitate its ubiquitination and proteasomal degradation in the cytoplasm...
June 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28627665/n-acetylcysteine-ameliorates-repetitive-stereotypic-behavior-due-to-its-antioxidant-properties-without-activation-of-the-canonical-wnt-pathway-in-a-valproic-acid-induced-rat-model-of-autism
#15
Yinghua Zhang, Weigang Cui, Qianqian Zhai, Tianran Zhang, Xiaojun Wen
N-acetylcysteine (NAC) is widely used as an antioxidant, and previous studies have suggested that it may have potential as an alternative therapeutic strategy for the treatment of patients with autism. However, the exact effects of NAC administration on the development of autism, as well as the molecular mechanisms underlying its actions, have yet to be fully elucidated. The present study aimed to investigate the effects of NAC on the oxidative status of rats in a valproic acid (VPA)‑induced model of autism, and to examine the involvement of the canonical Wnt signaling pathway in the actions of NAC...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627610/silencing-dek-downregulates-cervical-cancer-tumorigenesis-and-metastasis-via-the-dek-p-ser9-gsk-3%C3%AE-p-tyr216-gsk-3%C3%AE-%C3%AE-catenin-axis
#16
Xiaoyang Xu, Lin Zou, Qiuhui Yao, Yanbo Zhang, Li Gan, Liangdan Tang
Cervical cancer is the second most common gynecological malignancy. The mechanisms of the genesis and progression of cervical cancer are complicated and not thoroughly understood. DEK is reported as an oncogene in various cancers, such as acute myeloid leukemia, bladder cancer, breast cancer and hepatocellular cancer. However, its role in cervical cancer has not been well studied. In our study, we confirmed the DEK protein as an oncoprotein in cervical cancer tissues which is correlated to cervical cancer FIGO staging and tumor type...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627522/dot1l-safeguards-cartilage-homeostasis-and-protects-against-osteoarthritis
#17
Silvia Monteagudo, Frederique M F Cornelis, Carolina Aznar-Lopez, Ploi Yibmantasiri, Laura-An Guns, Peter Carmeliet, Frédéric Cailotto, Rik J Lories
Osteoarthritis is the most prevalent and crippling joint disease, and lacks curative treatment, as the underlying molecular basis is unclear. Here, we show that DOT1L, an enzyme involved in histone methylation, is a master protector of cartilage health. Loss of DOT1L disrupts the molecular signature of healthy chondrocytes in vitro and causes osteoarthritis in mice. Mechanistically, the protective function of DOT1L is attributable to inhibition of Wnt signalling, a pathway that when hyper-activated can lead to joint disease...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28627514/simultaneous-overactivation-of-wnt-%C3%AE-catenin-and-tgf%C3%AE-signalling-by-mir-128-3p-confers-chemoresistance-associated-metastasis-in-nsclc
#18
Junchao Cai, Lishan Fang, Yongbo Huang, Rong Li, Xiaonan Xu, Zhihuang Hu, Le Zhang, Yi Yang, Xun Zhu, Heng Zhang, Jueheng Wu, Yan Huang, Jun Li, Musheng Zeng, Erwei Song, Yukai He, Li Zhang, Mengfeng Li
Cancer chemoresistance and metastasis are tightly associated features. However, whether they share common molecular mechanisms and thus can be targeted with one common strategy remain unclear in non-small cell lung cancer (NSCLC). Here, we report that high levels of microRNA-128-3p (miR-128-3p) is key to concomitant development of chemoresistance and metastasis in residual NSCLC cells having survived repeated chemotherapy and correlates with chemoresistance, aggressiveness and poor prognosis in NSCLC patients...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28626941/binding-of-canonical-wnt-ligands-to-their-receptor-complexes-occurs-in-ordered-plasma-membrane-environments
#19
Erdinc Sezgin, Yagmur Azbazdar, Xue Wen Ng, Cathleen Teh, Kai Simons, Gilbert Weidinger, Thorsten Wohland, Christian Eggeling, Gunes Ozhan
While the cytosolic events of Wnt/β-catenin signaling (canonical Wnt signaling) pathway have been widely studied, only little is known about the molecular mechanisms involved in Wnt binding to its receptors at the plasma membrane. Here, we reveal the influence of the immediate plasma membrane environment on the canonical Wnt-receptor interaction. While the receptors are distributed both in ordered and disordered environments, Wnt binding to its receptors selectively occurs in more ordered membrane environments which appear to co-internalize with the Wnt-receptor complex...
June 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28626889/from-basal-cell-morphogenesis-to-the-alopecia-induced-by-hedgehog-inhibitors-connecting-the-dots
#20
REVIEW
C Dessinioti, C Antoniou, A J Stratigos
The deciphering of the hedgehog (Hh) signaling pathway implicated in the tumorigenesis of basal cell carcinoma (BCC), led to the development of targeted drug therapies, e.g. the hedgehog pathway inhibitors (HPI), vismodegib and sonidegib. In the skin, physiologic Hh signaling is activated in growing hair follicles, where it is required for proliferation of the epithelium of hair follicles during morphogenesis and for their postnatal growth. The effects of HPI treatment leading to the regression of BCC and the development of alopecia, underpin the central role of the Hh pathway in BCC formation as well as hair cycling...
June 18, 2017: British Journal of Dermatology
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