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Hox regulation

Cyrinne Achour, Francesca Aguilo
High-throughput analyses have revealed that the vast majority of the transcriptome does not code for proteins. These non-translated transcripts, when larger than 200 nucleotides, are termed long non-coding RNAs (lncRNAs), and play fundamental roles in diverse cellular processes. LncRNAs are subject to dynamic chemical modification, adding another layer of complexity to our understanding of the potential roles that lncRNAs play in health and disease. Many lncRNAs regulate transcriptional programs by influencing the epigenetic state through direct interactions with chromatin-modifying proteins...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
Ming-Rong Cao, Ze-Ping Han, Ji-Ming Liu, Yu-Guang Li, Yu-Bing Lv, Jia-Bin Zhou, Jin-Hua He
Computational analysis and bioinformatics have significantly advanced the ability of researchers to process and analyze biological data. Molecular data from human and model organisms may facilitate drug target validation and identification of biomarkers with increased predictive accuracy. The aim of the present study was to investigate the function of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) using online databases, and to predict their regulatory mechanism. HCC-associated lncRNAs, their downstream transcription factors and microRNAs (miRNAs/miRs), as well as the HCC-associated target genes, were identified using online databases...
May 2018: Oncology Letters
Pengxu Qian, Bony De Kumar, Xi C He, Christof Nolte, Madelaine Gogol, Youngwook Ahn, Shiyuan Chen, Zhenrui Li, Hanzhang Xu, John M Perry, Deqing Hu, Fang Tao, Meng Zhao, Yingli Han, Kate Hall, Allison Peak, Ariel Paulson, Chongbei Zhao, Aparna Venkatraman, Andrew Box, Anoja Perera, Jeffrey S Haug, Tari Parmely, Hua Li, Robb Krumlauf, Linheng Li
Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e...
May 3, 2018: Cell Stem Cell
Junhu Wan, Hongyang Liu, Quanling Feng, Jun Liu, Liang Ming
HOXB9, as a HOX family transcription factor, playing a significant role in embryonic development and cancer progression. However, the function of HOXB9 and its precise mechanism in regulating endometrial cancer progression remains unknown. Here, we demonstrated that the expression of HOXB9 was increased in endometrial cancer, and associated with histological grade and lymph node metastasis. In addition, elevated HOXB9 predicts a poor prognosis in endometrial cancer patients. Interestingly, bioinformatics analysis of TCGA cancer database showed that HOXB9 expression is positively correlated with E2F3 expression...
May 3, 2018: Cell Death & Disease
Hao Luo, Wei-Hui Liu, Hong-Yin Liang, Hong-Tao Yan, Ning Lin, Dong-Yu Li, Tao Wang, Li-Jun Tang
Background: Liver cancer stem cells (LCSCs) are the key factors for cancer metastasis, recurrent, and drug resistance. LCSCs are originated from either hepatocytes dedifferentiation or differentiation arresting of liver normal stem cells (LNSCs). Differentiation-inducing therapy is a novel strategy in solid tumors. Furthermore, Notch signaling pathway has been proved to play important role in the process of hepatocytes differentiation. In previous study, a malignant transformation cellular model of LNSCs has been built up, and in this study we are trying to illustrate whether inhibition of Notch can reverse this malignant tendency and drive these malignant cells back to differentiate into mature hepatocytes...
April 10, 2018: Oncotarget
Raj R Bhanvadia, Calvin VanOpstall, Hannah Brechka, Nimrod S Barashi, Marc Gillard, Erin M McAuley, Juan Apiz, Gladell P Paner, Wen-Ching Chan, Jorge Andrade, Angelo Demarzo, Misop Han, Russell Z Szmulewitz, Donald J Vander Griend
PURPOSE: Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS-HOX interactions in prostate cancer etiology and progression.  The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. EXPERIMENTAL DESIGN: Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Feng Wang, Zhongqiong Tang, Honglian Shao, Jun Guo, Tao Tan, Yang Dong, Lianbing Lin
The spatiotemporal control of HOX gene expression is dependent on positional identity and often correlated to their genomic location within each loci. Maintenance of HOX expression patterns is under complex transcriptional and epigenetic regulation, which is not well understood. Here we demonstrate that HOTTIP, a lincRNA transcribed from the 5' edge of the HOXA locus, physically associates with the CCCTC-binding factor (CTCF) that serves as an insulator by organizing HOXA cluster into disjoint domains, to cooperatively maintain the chromatin modifications of HOXA genes and thus coordinate the transcriptional activation of distal HOXA genes in human foreskin fibroblasts...
April 23, 2018: Biochemical and Biophysical Research Communications
Ji Hoon Oh, Clara Yuri Kim, Ji-Yeon Lee, Myoung Hee Kim
During the development of an embryo, the initiation of the collinear expression of Hox genes is essential for the proper formation of the anteroposterior body axis. Retinoic acid (RA), a natural derivative of vitamin A, plays a role in vertebrate development by regulating Hox gene expression. CCCTC-binding factor (CTCF), an insulator protein that controls gene transcription, also regulates the expression of Hox genes by binding to the CTCF-binding sites (CBSs). It has been reported that upon RA signaling, retinoic acid response elements (RAREs) located in the Hox clusters become occupied...
April 23, 2018: Acta Biochimica et Biophysica Sinica
Zhigang Xiao, Zhan Qu, Zhikang Chen, Zhixue Fang, Ke Zhou, Zhongcheng Huang, Xiong Guo, Yang Zhang
BACKGROUND/AIMS: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). METHODS: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells...
2018: Cellular Physiology and Biochemistry
Keri A Drake, Mike Adam, Robert Mahoney, S Steven Potter
Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance...
April 20, 2018: Scientific Reports
Maria Angeles Ros Lasierra, Marc Fernández-Guerrero, Lucille Delisle, Nayuta Yakushiji-Kaminatsui, Fabrice Darbellay, Rocío Pérez-Gómez, Denis Duboule
The developing vertebrate limb has long proved as an excellent system for studying the mechanisms involved in pattern formation and morphogenesis and more recently in transcriptional regulation and morphological evolution. To elucidate the stage-specific expression profiles of the components of the developing limb, we have generated the temporal transcriptome of the limb progenitors and of the overlying ectoderm separately. Our study has uncovered a collinear activation of Hoxc genes in the limb ectoderm that we have validated by in situ hybridization...
April 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Peder Aabel, Tor Paaske Utheim, Ole Kristoffer Olstad, Helge Rask-Andersen, Rodney James Dilley, Magnus von Unge
The human tympanic membrane (TM) has a thin outer epidermal layer which plays an important role in TM homeostasis and ear health. The specialised cells of the TM epidermis have a different physiology compared to normal skin epidermal keratinocytes, displaying a dynamic and constitutive migration that maintains a clear TM surface and assists in regeneration. Here, we characterise and compare molecular phenotypes in keratinocyte cultures from TM and normal skin. TM keratinocytes were isolated by enzymatic digestion and cultured in vitro...
April 5, 2018: Journal of the Association for Research in Otolaryngology: JARO
Vicente T Sedano-Núñez, Sjef Boeren, Alfons J M Stams, Caroline M Plugge
Syntrophobacter fumaroxidans is a sulfate-reducing bacterium able to grow on propionate axenically or in syntrophic interaction with methanogens or other sulfate-reducing bacteria. We performed a proteome analysis of S. fumaroxidans growing with propionate axenically with sulfate or fumarate, and in syntrophy with Methanospirillum hungatei, Methanobacterium formicicum or Desulfovibrio desulfuricans. Special attention was put on the role of hydrogen and formate in interspecies electron transfer (IET) and energy conservation...
April 3, 2018: Environmental Microbiology
Yunan Li, Mingying Zhang, Mengyao Sheng, Peng Zhang, Zizhen Chen, Wen Xing, Jie Bai, Tao Cheng, Feng-Chun Yang, Yuan Zhou
PURPOSE: Acute myeloid leukemia (AML) is a heterogeneous disease with poor outcomes. Despite increased evidence shows that dysregulation of histone modification contributes to AML, specific drugs targeting key histone modulators are not applied in the clinical treatment of AML. Here, we investigated whether targeting KDM6B, the demethylase of tri-methylated histone H3 lysine 27 (H3K27me3), has a therapeutic potential for AML. METHODS: A KDM6B-specific inhibitor, GSK-J4, was applied to treat the primary cells from AML patients and AML cell lines in vitro and in vivo...
March 28, 2018: Journal of Cancer Research and Clinical Oncology
Claudio Guedes Salgado, Pablo Pinto, Raquel Carvalho Bouth, Angélica Rita Gobbo, Ana Caroline Cunha Messias, Tatiana Vinasco Sandoval, André Mauricio Ribeiro Dos Santos, Fabiano Cordeiro Moreira, Amanda Ferreira Vidal, Luiz Ricardo Goulart, Josafá Gonçalves Barreto, Moisés Batista da Silva, Marco Andrey Cipriani Frade, John Stewart Spencer, Sidney Santos, Ândrea Ribeiro-Dos-Santos
Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease...
2018: Frontiers in Immunology
Emily V W Setton, Prashant P Sharma
The jointed appendages of arthropods have facilitated the spectacular diversity and success of this phylum. Key to the regulation of appendage outgrowth is the Krüppel-like factor (KLF)/specificity protein (Sp) family of zinc finger transcription factors. In the fruit fly, Drosophila melanogaster , the Sp6-9 homolog is activated by Wnt-1/wingless ( wg ) and establishes ventral appendage (leg) fate. Subsequently, Sp6-9 maintains expression of the axial patterning gene Distal-less ( Dll ), which promotes limb outgrowth...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alexander Tolkachov, Cornelius Fischer, Thomas H Ambrosi, Melissa Bothe, Chung-Ting Han, Matthias Muenzner, Susanne Mathia, Marjo Salminen, Georg Seifert, Mario Thiele, Georg N Duda, Sebastiaan H Meijsing, Sascha Sauer, Tim J Schulz, Michael Schupp
The transcription factor GATA2 is required for expansion and differentiation of hematopoietic stem cells (HSCs). In mesenchymal stem cells (MSCs) GATA2 blocks adipogenesis, but its biological relevance and underlying genomic events are unknown. We report a dual function of GATA2 in bone homeostasis. GATA2 in MSCs binds near genes involved in skeletal system development and co-localizes with motifs for FOX and HOX transcription factors, known regulators of skeletal development. Ectopic GATA2 blocks osteoblastogenesis by interfering with SMAD1/5/8 activation...
March 26, 2018: Molecular and Cellular Biology
Yanqing Xiao, Yanli Chen, Yanpeng Ding, Jie Wu, Peng Wang, Ya Yu, Xi Wei, Ye Wang, Chaojun Zhang, Fuguang Li, Xiaoyang Ge
The WUSCHEL (WUS) gene encodes a plant-specific homeodomain-containing transcriptional regulator, which plays important roles during embryogenesis, as well as in the formation of shoot and flower meristems. Here, we isolated two homologues of Arabidopsis thaliana WUS (AtWUS), GhWUS1a_At and GhWUS1b_At, from upland cotton (Gossypium hirsutum). Domain analysis suggested that the two putative GhWUS proteins contained a highly conserved DNA-binding HOX domain and a WUS-box. Expression profile analysis showed that GhWUSs were predominantly expressed during the embryoid stage...
May 2018: Plant Science: An International Journal of Experimental Plant Biology
Yan Zhang, Xiaoling Cheng, Hua Liang, Zhenzhen Jin
Homeobox (HOX) transcript antisense RNA (HOTAIR) is a long intergenic non-coding RNA (lncRNA) that has been reported to be highly upregulated in several types of cancers. However, the role of HOTAIR in human cervical cancer is still unclear. We therefore investigated the expression and probable function of HOTAIR in cervical cancer cells. The expression of HOTAIR was examined in (HeLa, CaSki, ME-180, HT-3) and Human Cervical Epithelial Cells (HCerEpiC) by qRT-PCR. Transfection of si-NC, si-HOTAIR or si-STAT3 was carried out with the help of Lipofectamine 2000...
March 20, 2018: Chemico-biological Interactions
Hugo J Parker, Irina Pushel, Robb Krumlauf
The neural crest is a transient population of cells that forms within the developing central nervous system and migrates away to generate a wide range of derivatives throughout the body during vertebrate embryogenesis. These cells are of evolutionary and clinical interest, constituting a key defining trait in the evolution of vertebrates and alterations in their development are implicated in a high proportion of birth defects and craniofacial abnormalities. In the hindbrain and the adjacent cranial neural crest cells (cNCCs), nested domains of Hox gene expression provide a combinatorial'Hox-code' for specifying regional properties in the developing head...
March 20, 2018: Developmental Biology
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