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Tim van Groningen, Jan Koster, Linda J Valentijn, Danny A Zwijnenburg, Nurdan Akogul, Nancy E Hasselt, Marloes Broekmans, Franciska Haneveld, Natalia E Nowakowska, Johannes Bras, Carel J M van Noesel, Aldo Jongejan, Antoine H van Kampen, Linda Koster, Frank Baas, Lianne van Dijk-Kerkhoven, Margriet Huizer-Smit, Maria C Lecca, Alvin Chan, Arjan Lakeman, Piet Molenaar, Richard Volckmann, Ellen M Westerhout, Mohamed Hamdi, Peter G van Sluis, Marli E Ebus, Jan J Molenaar, Godelieve A Tytgat, Bart A Westerman, Johan van Nes, Rogier Versteeg
Neuroblastoma and other pediatric tumors show a paucity of gene mutations, which has sparked an interest in their epigenetic regulation. Several tumor types include phenotypically divergent cells, resembling cells from different lineage development stages. It has been proposed that super-enhancer-associated transcription factor (TF) networks underlie lineage identity, but the role of these enhancers in intratumoral heterogeneity is unknown. Here we show that most neuroblastomas include two types of tumor cells with divergent gene expression profiles...
June 26, 2017: Nature Genetics
W A da Silveira, P V B Palma, R D Sicchieri, R A R Villacis, L R M Mandarano, T M G Oliveira, H M R Antonio, J M Andrade, V F Muglia, S R Rogatto, C Theillet, S du Manoir, D G Tiezzi
Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype...
June 6, 2017: Scientific Reports
Yamu Li, Wen Wang, Fangyu Wang, Qiushuang Wu, Wei Li, Xiaoling Zhong, Kuan Tian, Tao Zeng, Liang Gao, Ying Liu, Shu Li, Xiaobing Jiang, Guangwei Du, Yan Zhou
Glioblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent studies indicate that glioma-initiating cells/glioma stem cells (GICs/GSCs) may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 (PRRX1), a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation...
May 9, 2017: Journal of Molecular Cell Biology
Hongbin Zhu, Gengyun Sun
Epithelial-mesenchymal transition (EMT) plays crucial role in tumor metastasis and patient prognosis. Previous studies indicated that paired-related homeobox 1 (PRRX1), a newly identified EMT inducer, plays opposing roles in different tumor cell types. However, the function of PRRX1 in lung cancer has not been elucidated. In the present study, we observed that the expression level of PRRX1 was high in A549 cells, and a loss of PRRX1 induced EMT by regulating the EMT markers N-cadherin, E-cadherin and vimentin in A549 cells...
2017: American Journal of Translational Research
Shigetoshi Yokoyama, Soichi Furukawa, Shoya Kitada, Masaki Mori, Takeshi Saito, Koichi Kawakami, Juan Carlos Izpisua Belmonte, Yasuhiko Kawakami, Yoshiaki Ito, Tempei Sato, Hiroshi Asahara
Limb bud patterning, outgrowth, and differentiation are precisely regulated in a spatio-temporal manner through integrated networks of transcription factors, signaling molecules, and downstream genes. However, the exact mechanisms that orchestrate morphogenesis of the limb remain to be elucidated. Previously, we have established EMBRYS, a whole-mount in situ hybridization database of transcription factors. Based on the findings from EMBRYS, we focused our expression pattern analysis on a selection of transcription factor genes that exhibit spatially localized and temporally dynamic expression patterns with respect to the anterior-posterior axis in the E9...
2017: PloS One
Ji-Young Lee, Tae-Hoon Kim, Pil-Sung Yang, Hong Euy Lim, Eue-Keun Choi, Jaemin Shim, Eunsoon Shin, Jae-Sun Uhm, Jin-Seok Kim, Boyoung Joung, Seil Oh, Moon-Hyoung Lee, Young-Hoon Kim, Hui-Nam Pak
Aims: Some genetic susceptibility loci for atrial fibrillation (AF) identified by genome-wide association studies (GWAS) in a European database showed ethnic differences in the Asian population. We explored novel AF susceptibility variants for patients with early-onset AF (≤60 years old) among Korean patients who underwent AF catheter ablation. Methods and results: A genome-wide association study (GWAS) was conducted with 672 cases (≤60 years old, Yonsei AF Ablation cohort) and 3700 controls (Korea Genome Epidemiology Study)...
April 27, 2017: European Heart Journal
Hongbin Zhu, Gengyun Sun, Jiahui Dong, Liming Fei
Paired related homeobox1 (PRRX1) was a newly identified Epithelial mesenchymal transition (EMT) inducer. It was found that the decreased expression of PRRX1 in breast cancer and liver cancer could enable tumor cells to obtain tumor stem cell characteristics in vitro studies. However, the role of PRRX1 in lung cancer was still unknown. The down-regulated PRRX1 gene in A549 cells was established by slow virus infection in this study. The apoptosis of A549 cells was observed after the treatment of different concentrations of cisplatin and the role of PRRX1 in the apoptosis of A549 cells was explored...
2017: American Journal of Translational Research
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
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