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Lian Liu, Yusuke Ebana, Jun-Ichi Nitta, Yoshihide Takahashi, Shinsuke Miyazaki, Toshihiro Tanaka, Masatoshi Komura, Mitsuaki Isobe, Tetsushi Furukawa
BACKGROUND: Atrial fibrillation (AF) affects millions of individuals worldwide. The genome-wide association studies have identified robust genetic associations with AF. METHODS: We genotyped 5461 participants of Japanese ancestry for 11 AF-related loci and determined the effects of carrying different numbers of risk alleles on disease development and age at disease onset. The weighted genetic risk score (GRS) was calculated, and its ability to predict AF was determined...
November 4, 2016: Canadian Journal of Cardiology
Kotaro Horiguchi, Hideji Yako, Saishu Yoshida, Ken Fujiwara, Takehiro Tsukada, Naoko Kanno, Hiroki Ueharu, Hiroto Nishihara, Takako Kato, Takashi Yashiro, Yukio Kato
The anterior and intermediate lobes of the pituitary gland develop through invagination of the oral ectoderm and as they are endocrine tissues, they participate in the maintenance of vital functions via the synthesis and secretion of numerous hormones. We recently observed that several extrapituitary cells invade the anterior lobe of the developing pituitary gland. This raised the question of the origin(s) of these S100β-positive cells, which are not classic endocrine cells but instead comprise a heterogeneous cell population with plural roles, especially as stem/progenitor cells...
2016: PloS One
Shui-Miao Lin, Qiong Xia, Yu-Qin Zhang, Ai-Min Sun, Yu-Sheng Shi, Lin Zheng, Long-Hua Chen
OBJECTIVE: To detect the expression of miR-124 in colorectal carcinoma (CRC) cells and tissue specimens and analyze its association with the radiosensitivity of the cells. METHODS: The expression of miR-124 in CRC cell lines and tissues were detected using qRT-PCR. The effect of miR-124 in modulating cell radiosensitivity was assessed in CRC cells with miRNA-124 overexpression and miRNA-124 knockdown, and bioinformatics prediction and dual luciferase reporter system were employed to identify the direct target of miR-124...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Yen-Hao Su, Wen-Chien Huang, Tse-Hung Huang, Yan-Jiun Huang, Yu-Kai Sue, Thanh-Tuan Huynh, Michael Hsiao, Tsan-Zon Liu, Alexander Th Wu, Chien-Min Lin
Clinically, serum level of folate has been negatively correlated to the stage and progression of liver cancer. Nevertheless, the functional consequence of folate deficiency (FD) in malignancy has not been fully investigated. Human hepatocellular carcinoma (HCC) cells (as study model) and other cancer types such as lung and glioma were cultured under folate deficient (FD) and folate complete (FD) conditions. Molecular characterization including intracellular ROS/RNS (reactive oxygen/nitrogen species), viability, colony formation, cancer stem-like cell (CSC) phenotype analyses were performed...
May 31, 2016: Oncotarget
Lindsey Barske, Amjad Askary, Elizabeth Zuniga, Bartosz Balczerski, Paul Bump, James T Nichols, J Gage Crump
The intricate shaping of the facial skeleton is essential for function of the vertebrate jaw and middle ear. While much has been learned about the signaling pathways and transcription factors that control facial patterning, the downstream cellular mechanisms dictating skeletal shapes have remained unclear. Here we present genetic evidence in zebrafish that three major signaling pathways - Jagged-Notch, Endothelin1 (Edn1), and Bmp - regulate the pattern of facial cartilage and bone formation by controlling the timing of cartilage differentiation along the dorsoventral axis of the pharyngeal arches...
April 2016: PLoS Genetics
Zhi-Dong Lv, Zhao-Chuan Yang, Xiang-Ping Liu, Li-Ying Jin, Qian Dong, Hui-Li Qu, Fu-Nian Li, Bin Kong, Jiao Sun, Jiao-Jiao Zhao, Hai-Bo Wang
Triple-negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The mechanisms involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumour subtype. Paired-related homeobox 1b (Prrx1b), one of major isoforms of Prrx1, has been identified as a new epithelial-mesenchymal transition (EMT) inducer. However, the function of Prrx1b in TNBC has not been elucidated. In this study, we found that Prrx1b was significantly up-regulated in TNBC and associated with tumour size and vascular invasion of breast cancer...
September 2016: Journal of Cellular and Molecular Medicine
Aimin Li, Shudong Ma, Susan M Smith, Matt K Lee, Ashley Fischer, Zea Borok, Saverio Bellusci, Changgong Li, Parviz Minoo
BACKGROUND: Epithelial-mesenchymal cross talk is centerpiece in the development of many branched organs, including the lungs. The embryonic lung mesoderm provides instructional information not only for lung architectural development, but also for patterning, commitment and differentiation of its many highly specialized cell types. The mesoderm also serves as a reservoir of progenitors for generation of differentiated mesenchymal cell types that include αSMA-expressing fibroblasts, lipofibroblasts, endothelial cells and others...
March 16, 2016: BMC Biology
Mark O Kitchen, Richard T Bryan, Richard D Emes, John R Glossop, Christopher Luscombe, K K Cheng, Maurice P Zeegers, Nicholas D James, Adam J Devall, Charles A Mein, Lyndon Gommersall, Anthony A Fryer, William E Farrell
High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls...
March 3, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Zhi-Dong Lv, Bin Kong, Xiang-Ping Liu, Li-Ying Jin, Qian Dong, Fu-Nian Li, Hai-Bo Wang
Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. The epithelial-to-mesenchymal transition (EMT) is a key contributor in the metastatic process. In this study, we found that miR-655 was down-regulated in TNBC, and its expression levels were associated with molecular-based classification and lymph node metastasis in breast cancer. These findings led us to hypothesize that miR-655 overexpression may inhibit EMT and its associated traits of TNBC...
May 2016: Journal of Cellular and Molecular Medicine
Shigetsugu Takano, Maximilian Reichert, Basil Bakir, Koushik K Das, Takahiro Nishida, Masaru Miyazaki, Steffen Heeg, Meredith A Collins, Benoît Marchand, Philip D Hicks, Anirban Maitra, Anil K Rustgi
The two major isoforms of the paired-related homeodomain transcription factor 1 (Prrx1), Prrx1a and Prrx1b, are involved in pancreatic development, pancreatitis, and carcinogenesis, although the biological role that these isoforms serve in the systemic dissemination of pancreatic ductal adenocarcinoma (PDAC) has not been investigated. An epithelial-mesenchymal transition (EMT) is believed to be important for primary tumor progression and dissemination, whereas a mesenchymal-epithelial transition (MET) appears crucial for metastatic colonization...
January 15, 2016: Genes & Development
Lin Zheng, Yuqin Zhang, Shuimiao Lin, Aimin Sun, Runze Chen, Yi Ding, Yanqing Ding
Accumulating evidence identified that epithelial-mesenchymal transition (EMT) is acquired during progression to metastatic, but whether it is an absolute requirement is still controversial. MiR-106b has been confirmed to promote cancer cell proliferation; however few studies are available on its functions in EMT and metastasis in colorectal cancer (CRC). In this study, we found that knocking down miR-106b induced EMT conferring migratory and invasive properties. MiR-106b knockdown induced cytoskeletal reorganization through staining intracellular F-actin...
2015: International Journal of Clinical and Experimental Pathology
Amel Dudakovic, Emily T Camilleri, Fuhua Xu, Scott M Riester, Meghan E McGee-Lawrence, Elizabeth W Bradley, Christopher R Paradise, Eric A Lewallen, Roman Thaler, David R Deyle, A Noelle Larson, David G Lewallen, Allan B Dietz, Gary S Stein, Martin A Montecino, Jennifer J Westendorf, Andre J van Wijnen
Epigenetic control of gene expression is critical for normal fetal development. However, chromatin-related mechanisms that activate bone-specific programs during osteogenesis have remained underexplored. Therefore, we investigated the expression profiles of a large cohort of epigenetic regulators (>300) during osteogenic differentiation of human mesenchymal cells derived from the stromal vascular fraction of adipose tissue (AMSCs). Molecular analyses establish that the polycomb group protein EZH2 (enhancer of zeste homolog 2) is down-regulated during osteoblastic differentiation of AMSCs...
November 13, 2015: Journal of Biological Chemistry
Mamata F Khirade, Girdhari Lal, Sharmila A Bapat
The hallmarks of cancer deem biological pathways and molecules to be conserved. This approach may be useful for deriving a prognostic gene signature. Weighted Gene Co-expression Network Analysis of gene expression datasets in eleven cancer types identified modules of highly correlated genes and interactive networks conserved across glioblastoma, breast, ovary, colon, rectal and lung cancers, from which a universal classifier for tumor stratification was extracted. Specific conserved gene modules were validated across different microarray platforms and datasets...
2015: Scientific Reports
Estefanía Lozano-Velasco, Francisco Hernández-Torres, Houria Daimi, Selma A Serra, Adela Herraiz, Leif Hove-Madsen, Amelia Aránega, Diego Franco
AIMS: Atrial fibrillation (AF) is the most common type of arrhythmia in humans, yet the genetic cause of AF remains elusive. Genome-wide association studies (GWASs) have reported risk variants in four distinct genetic loci, and more recently, a meta-GWAS has further implicated six new loci in AF. However, the functional role of these AF GWAS-related genes in AF and their inter-relationship remain elusive. METHODS AND RESULTS: To get further insights into the molecular mechanisms driven by Pitx2, calcium handling and novel AF GWAS-associated gene expression were analysed in two distinct Pitx2 loss-of-function models with distinct basal electrophysiological defects; a novel Pitx2 conditional mouse line, Sox2CrePitx2, and our previously reported atrial-specific NppaCrePitx2 line...
January 1, 2016: Cardiovascular Research
C Cerutti, C Z Paultre, M P Gustin, O Lohez, P Feugier, J Y Li, G Bricca
OBJECTIVE: During atherogenesis, vascular smooth muscle cells (VSMCs) undergo a phenotypic modulation leading to migration and loss of contractility. Here we propose a gene regulatory network specific of the contractile phenotype of the carotid VSMCs from transcriptomic data. DESIGN AND METHOD: Human carotid atheroma plaque (ATH, Stary>4) and nearby macroscopically intact tissue (MIT, Stary<3) of 32 patients were analysed by microarrays (Affymetrix HuGene-1...
June 2015: Journal of Hypertension
Adelaida R Palla, Daniela Piazzolla, Noelia Alcazar, Marta Cañamero, Osvaldo Graña, Gonzalo Gómez-López, Orlando Dominguez, Marta Dueñas, Jesús M Paramio, Manuel Serrano
NANOG is a key pluripotency factor in embryonic stem cells that is frequently expressed in squamous cell carcinomas (SCCs). However, a direct link between NANOG and SCCs remains to be established. Here, we show that inducible overexpression of NANOG in mouse skin epithelia favours the malignant conversion of skin papillomas induced by chemical carcinogenesis, leading to increased SCC formation. Gene expression analyses in pre-malignant skin indicate that NANOG induces genes associated to epithelial-mesenchymal transition (EMT)...
May 19, 2015: Scientific Reports
Masanori Murakami, Takanobu Yoshimoto, Kazuhiko Nakabayashi, Kyoichiro Tsuchiya, Isao Minami, Ryotaro Bouchi, Hajime Izumiyama, Yasuhisa Fujii, Kosei Abe, Chiharu Tayama, Koshi Hashimoto, Takayoshi Suganami, Ken-ichiro Hata, Kazunori Kihara, Yoshihiro Ogawa
OBJECTIVE: The pathophysiology of aldosterone-producing adenomas (APA) has been investigated intensively through genetic and genomic approaches. However, the role of epigenetics in APA is not fully understood. In the present study, we explored the relationship between gene expression and DNA methylation status in APA. METHODS: We conducted an integrated analysis of transcriptome and methylome data of paired APA-adjacent adrenal gland (AAG) samples from the same patient...
August 2015: European Journal of Endocrinology
Shanshan Chen, Chuchu Wang, Xiaojing Wang, Chengqi Xu, Manman Wu, Pengxia Wang, Xin Tu, Qing K Wang
BACKGROUND: Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies. METHODS AND RESULTS: Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls...
May 2015: Journal of the American Heart Association
D H Jensen, E Dabelsteen, L Specht, A M K Fiehn, M H Therkildsen, L Jønson, J Vikesaa, F C Nielsen, C von Buchwald
Although tumour budding is an adverse prognostic factor for many cancer types, the molecular mechanisms governing this phenomenon are incompletely understood. Therefore, understanding the molecular basis of tumour budding may provide new therapeutic and diagnostic options. We employ digital image analysis to demonstrate that the number of tumour buds in cytokeratin-stained sections correlates with patients having lymph node metastases at diagnosis. The tumour bud count was also a predictor of overall survival, independent of TNM stage...
August 2015: Journal of Pathology
Mengchen Zhou, Yuhua Liao, Xin Tu
Atrial fibrillation (AF) is a complex disease that results from genetic and environmental factors and their interactions. In recent years, genome-wide association studies (GWAS) and family-based linkage analysis have found amounts of genetic variants associated with AF. Some of them lie in coding sequences and thus mediate the encoded proteins, some in non-coding regions and influence the expression of adjacent genes. These variants exert influence on the development of cardiovascular system and normal cardiac electrical activity in different levels, and eventually contribute to the occurrence of AF...
February 2015: Journal of Thoracic Disease
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