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Peng Liu, Teng-Fei Zhou, Bao-An Qiu, Ying-Xiang Yang, Yong-Jian Zhu, Yang An, Wen-Chao Zhao, Yin-Tao Wu, Peng-Fei Ma, Jing-Bo Li, Nian-Xin Xia
Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies, accounting for about 3% of all gastrointestinal tumors. GATA5 is a transcription factor capable of suppressing the development of various human cancer types. Transcriptional inactivation and CpG island (CGI) methylation of GATA3 and GATA5, two members of the GATA family of transcription factors, have been observed in some human cancers. But whether high-density CGI methylation of GATA5 is associated with the clinical course of CCA patients has not been clarified...
March 13, 2018: Translational Oncology
Yu Shi, Wenguang Liu, Maoxian He
Bivalve mollusks exhibit hermaphroditism and sex reversal/differentiation. Studies generally focus on transcriptional profiling and specific genes related to sex determination and differentiation. Few studies on sex reversal/differentiation have been reported. A combination analysis of gonad proteomics and transcriptomics was conducted on Chlamys nobilis to provide a systematic understanding of sex reversal/differentiation in bivalves. We obtained 4258 unique peptides and 93,731 unigenes with good correlation between messenger RNA and protein levels...
March 15, 2018: Marine Biotechnology
Sribalasubashini Muralimanoharan, Youn-Tae Kwak, Carole R Mendelson
Dysregulation of human trophoblast invasion and differentiation with placental hypoxia can result in preeclampsia, a hypertensive disorder of pregnancy. Herein, we characterized the role and regulation of miR-1246, which is markedly induced during human syncytiotrophoblast differentiation. miR-1246 is known to target GSK3β and AXIN2, inhibitors of WNT/β-catenin signaling, which is crucial for placental development, and is predicted to target JARID2, which promotes silencing of developmentally regulated genes...
March 13, 2018: Endocrinology
Haiying Rao, Yuxiang Bai, Qingshu Li, Baimei Zhuang, Yu Yuan, Yamin Liu, Wei Peng, Philip N Baker, Chao Tong, Xin Luo, Hongbo Qi
Preeclampsia (PE) is characterized by abnormal placentation in the early stages of pregnancy. Adequate migration and invasion of trophoblasts into the uterine wall and spiral arteries to form a functional maternal-fetal interface are pivotal for normal placentation, but the exact mechanism remains unclear. Growing evidence has revealed that special AT-rich sequence-binding protein 1 (SATB1) is a tumor promoter that participates in cancer cell migration and invasion. However, the expression and function of SATB1 in trophoblasts is unknown...
March 13, 2018: Biology of Reproduction
Jie Li, Liqiang Li, Yong Shen
The present study aimed to investigate the role of microRNA (miR)-219-5p in spinal cord injury (SCI) and to examine the underlying molecular mechanism. SCI rat and cell models were conducted in the current study, while reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of miR-219-5p in the SCI mice and neurons. Bioinformatics analysis was applied to predict the target genes of miR-219-5p, and dual-luciferase reporter assay was performed to verify the prediction...
April 2018: Experimental and Therapeutic Medicine
Hong Qi, Aiping Li
The present study aimed to investigate the effects of JWA knockout (JWA-/- ) on malignant transformation of murine embryonic fibroblast (MEF) cells using a conditional JWA-/- mouse model. Once MEF cells were prepared, the potential role of JWA-/- on proliferation, migration, invasion and colony formation of MEF cells was investigated by cytological examination. The effects of JWA-/- on the regulation and protein expression levels of epithelial-mesenchymal transition (EMT)-related proteins in MEF cells, including poly(ADP-ribose) polymerase-1 (PARP-1), vimentin, β-catenin and E-cadherin, were investigated using western blot analysis...
April 2018: Experimental and Therapeutic Medicine
Tian-Xing Chen, Xiao-Ying Cheng, Yun Wang, Wu Yin
Toosendanin (TSN), a triterpenoid extracted from Melia toosendan, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. However, its anti-adipogenic effect remains unknown. Here, we found that TSN dose-dependently attenuated lipid accumulation in preadipocytes 3T3-L1 as evidenced by Oil Red O staining. TSN also significantly downregulated mRNA and protein levels of adipocytokines (adiponectin and leptin), CCAAT/enhancer binding proteins α (C/EBP-α), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase, and acetyl-CoA carboxylase in adipocytes...
March 15, 2018: Scientific Reports
Hyeon Jeong Lee, Jie Li, Renee E Vickman, Junjie Li, Rui Liu, Abigail Durkes, Bennett D Elzey, Shuhua Yue, Xiaoqi Liu, Timothy L Ratliff, Ji-Xin Cheng
Dysregulation of cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of cholesterol esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intra-cardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis...
March 15, 2018: Molecular Cancer Research: MCR
Virginia Piombo, Katja Jochmann, Daniel Hoffmann, Manuela Wuelling, Andrea Vortkamp
Multiple osteochondromas (MO) syndrome is a dominant autosomal bone disorder characterized by the formation of cartilage-capped bony outgrowths that develop at the juxtaposition of the growth plate of endochondral bones. MO has been linked to mutations in either EXT1 or EXT2, two glycosyltransferases required for the synthesis of heparan sulfate (HS). The establishment of mouse mutants demonstrated that a clonal, homozygous loss of Ext1 in a wild type background leads to the development of osteochondromas. Here we investigate mechanisms that might contribute to the variation in the severity of the disease observed in human patients...
March 12, 2018: Bone
Jun Zhan, Hongquan Zhang
The Kindlins are FERM domain proteins comprising three members (Kindlin-1, -2 and -3) which are evolutionarily conserved. Kindlins bind with β-integrin cytoplasmic tails and execute broad biological functions including directed cell migration, proliferation, differentiation and survival. In light of more and more evidence point to the importance of Kindlin family members in normal development and human diseases especially in cancers, we aim to portrait the profile of Kindlins in the regulation of embryonic development and cancer progression...
March 12, 2018: International Journal of Biochemistry & Cell Biology
Joanna Przybyl, Lukasz Kidzinski, Trevor Hastie, Maria Debiec-Rychter, Roel Nusse, Matt van de Rijn
OBJECTIVE: Low-grade endometrial stromal sarcomas (LGESS) harbor chromosomal translocations that affect proteins associated with chromatin remodeling Polycomb Repressive Complex 2 (PRC2), including SUZ12, PHF1 and EPC1. Roughly half of LGESS also demonstrate nuclear accumulation of β-catenin, which is a hallmark of Wnt signaling activation. However, the targets affected by the fusion proteins and the role of Wnt signaling in the pathogenesis of these tumors remain largely unknown. METHODS: Here we report the results of a meta-analysis of three independent gene expression profiling studies on LGESS and immunohistochemical evaluation of nuclear expression of β-catenin and Lef1 in 112 uterine sarcoma specimens obtained from 20 LGESS and 89 LMS patients...
March 12, 2018: Gynecologic Oncology
Yoshinori Hirano, Yu Amano, Shigenobu Yonemura, Toshio Hakoshima
Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G...
March 15, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
John R Apps, Gabriela Carreno, Jose Mario Gonzalez-Meljem, Scott Haston, Romain Guiho, Julie E Cooper, Saba Manshaei, Nital Jani, Annett Hölsken, Benedetta Pettorini, Robert J Beynon, Deborah M Simpson, Helen C Fraser, Ying Hong, Shirleen Hallang, Thomas J Stone, Alex Virasami, Andrew M Donson, David Jones, Kristian Aquilina, Helen Spoudeas, Abhijit R Joshi, Richard Grundy, Lisa C D Storer, Márta Korbonits, David A Hilton, Kyoko Tossell, Selvam Thavaraj, Mark A Ungless, Jesus Gil, Rolf Buslei, Todd Hankinson, Darren Hargrave, Colin Goding, Cynthia L Andoniadou, Paul Brogan, Thomas S Jacques, Hywel J Williams, Juan Pedro Martinez-Barbera
Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset...
March 14, 2018: Acta Neuropathologica
Xuren Gao, Jian Ge, Weiyi Li, Wangchen Zhou, Lei Xu
Background: Resveratrol (RSV) has been reported to stimulate osteoblast differentiation in which Wnt/β-catenin signaling pathway played a crucial role. However, whether and how RSV activated Wnt/β-catenin pathway in osteogenic differentiation still remained elusive. Methods: In vivo polymethylmethacrylate (PMMA) particle-induced osteolysis (PIO) mouse model and in vitro PMMA particle-stimulated mouse mesenchymal stem cells (mMSCs) experiments were established...
2018: Cell & Bioscience
Ursula J Lemberger, Claudia D Fuchs, Christian Schöfer, Andrea Bileck, Christopher Gerner, Tatjana Stojakovic, Makoto M Taketo, Michael Trauner, Gerda Egger, Christoph H Österreicher
Background: Wnt/β-catenin signaling plays a crucial role in embryogenesis, tissue homeostasis, metabolism and malignant transformation of different organs including the liver. Continuous β-catenin signaling due to somatic mutations in exon 3 of the Ctnnb1 gene is associated with different liver diseases including cancer and cholestasis. Results: Expression of a degradation resistant form of β-catenin in hepatocytes resulted in 100% mortality within 31 days after birth...
February 16, 2018: Oncotarget
Heather L Lehman, Michal Kidacki, Joshua I Warrick, Douglas B Stairs
Four out of five patients diagnosed with esophageal squamous cell carcinoma (ESCC) will die within five years. This is primarily a result of the aggressive invasive potential of the disease. Our research is focused on the interplay between tumor suppressors and oncogenes in the invasive process. Specifically, EGFR and p120-catenin (p120ctn) are commonly dysregulated genes that are indicative of poor prognosis in ESCC. In a previous study we demonstrated that in our 3D organotypic culture model, only when EGFR overexpression is combined with p120ctn inactivation do the cells transform and invade - as opposed to either event alone...
February 16, 2018: Oncotarget
Takahiro Yoshida, Nikolai A Sopko, Max Kates, Xiaopu Liu, Gregory Joice, David J McConkey, Trinity J Bivalacqua
There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ . Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells...
February 16, 2018: Oncotarget
Cheng-Hung Chuang, Li-Yu Wang, Yuen Man Wong, En-Shyh Lin
Metastatic lung cancer is a leading cause of mortality and has a mortality rate of ≥90%. Isolinderalactone (ILL) is a sesquiterpene lactone compound that has been used in traditional Chinese medicine. Research has demonstrated that ILL has anti-inflammatory and anti-proliferative properties; however, to the best of our knowledge, studies investigating whether ILL can inhibit lung cancer cell metastasis have not been conducted. In the present study, 1-10 µM ILL was applied in the culturing of the A549 lung cancer cell line to investigate the effects of ILL on the invasion and migration of lung cancer cells, including whether the possible mechanisms of ILL are associated with the expression of matrix metalloproteinase (MMP)-2 and NME/NM23 nucleoside diphosphate kinase 1 (NM23-H1) genes...
April 2018: Oncology Letters
Yanchun Ma, Kun Chen, Zhenhua Yang, Ming Guan
Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform...
April 2018: Oncology Letters
Guangzhong Xu, Kai Li, Nengwei Zhang, Bin Zhu, Guosheng Feng, Qing Fan
Colorectal cancer is a common malignancy with a high prevalence and associated mortality rate. However, the preclinical tools currently used for drug development are insufficient. The aim of the present study was to establish and characterize a specific patient-derived colon cancer xenograft (PDCCX) mouse model for drug testing. Primary colon tumors were obtained from 10 patients by surgical resection, and tumor tissues were subsequently grafted into nude mice followed by consecutive passages. Primary tumors and xenograft tumors were collected and processed for DNA sequencing, histological evaluation and immunohistochemical staining...
April 2018: Oncology Letters
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