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Hox regulation

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https://www.readbyqxmd.com/read/28546992/identification-of-transcription-factors-potentially-involved-in-human-adipogenesis-in%C3%A2-vitro
#1
Melvin Anyasi Ambele, Michael Sean Pepper
BACKGROUND: Increased adiposity in humans leads to obesity, which is a major risk factor for cardiovascular disease, type 2 diabetes, and cancer. We previously conducted an extensive unbiased in vitro transcriptomic analysis of adipogenesis, using human adipose-derived stromal cells (ASCs). Here, we have applied computational methods to these data to identify transcription factors (TFs) that constitute the upstream gene regulatory networks potentially, driving adipocyte formation in human ASCs...
May 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28541373/the-histone-acetylation-mediated-by-gcn5-regulates-the-hoxc11-gene-expression-in-mefs
#2
Ji Hoon Oh, Ji-Yeon Lee, Kyoung-Ah Kong, Jie Min Kim, Myoung Hee Kim
Hox genes are responsible for encoding transcription factors that are essential for anterior-posterior body patterning at early stages of embryogenesis. However, detailed mechanisms of Hox genes are yet to be defined. Protein kinase B alpha (Akt1) was previously identified as a possible upstream regulator of Hox genes. Furthermore, the Hoxc11 gene has been upregulated in Akt1 null (Akt1-/-) mouse embryonic fibroblasts (MEFs), while repressed in wild-type MEFs. In this study, we propose to investigate the role of Gcn5, a histone acetyltransferase, in the regulation of Hoxc11 expression in MEFs...
May 24, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28534516/transcriptional-and-posttranscriptional-regulation-of-hoxa13-by-lncrna-hottip-facilitates-tumorigenesis-and-metastasis-in-esophageal-squamous-carcinoma-cells
#3
C Lin, Y Wang, Y Wang, S Zhang, L Yu, C Guo, H Xu
The long non-coding RNA, HOTTIP, has an important role in tumorigenesis. It is known that HOTTIP regulates HOX gene family; however, its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains elusive. In this study, we investigated the role of HOTTIP in ESCC and observed that HOTTIP/HOXA13 was upregulated in ESCC and promoted cell proliferation and metastasis in vivo and in vitro. Interestingly, harboring a miR-30b-binding site, HOTTIP as a molecular sponge mainly regulated miR-30b level in the nucleus and modulated the repression of HOXA13 mediated by miR-30b in the cytoplasm, resulting in the positive HOTTIP/HOXA13 correlation...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28529621/hoxa5-and-p53-cooperate-to-suppress-lung-cancer-cell-invasion-and-serve-as-good-prognostic-factors-in-non-small-cell-lung-cancer
#4
Chi-Jen Chang, Yen-Lin Chen, Chia-Hung Hsieh, Ya-Jung Liu, Sung-Liang Yu, Jeremy J W Chen, Chi-Chung Wang
Lung cancer is the leading cause of cancer mortality worldwide and tumor metastasis is the major cause of cancer-related death. Our previous study suggested that Homeobox A5 (HOXA5) could inhibit lung cancer cell invasion via regulating cytoskeletal remodeling and involved in tumor metastasis. Recently, consensus HOX binding sites was found in the p53 gene promoter region. However, whether the HOXA5 could cooperate with p53 and contribute the inhibition of lung cancer cell invasion is still unclear. The aim of the current study is to elucidate the correlation of HOXA5 and p53 in tumor invasion and its prognostic influence in lung cancer patient specimens...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28515451/hoxa7-hoxa9-and-hoxa10-are-differentially-expressed-in-clival-and-sacral-chordomas
#5
Daniela Jäger, Thomas F E Barth, Silke Brüderlein, Angelika Scheuerle, Beate Rinner, Adrian von Witzleben, André Lechel, Patrick Meyer, Regine Mayer-Steinacker, Alexandra von Baer, Markus Schultheiss, Christian R Wirtz, Peter Möller, Kevin Mellert
Chordomas are rare tumours of the bone arising along the spine from clivus to sacrum. We compared three chordoma cell lines of the clivus region including the newly established clivus chordoma cell line, U-CH14, with nine chordoma cell lines originating from sacral primaries by morphology, on genomic and expression levels and with patient samples from our chordoma tissue bank. Clinically, chordomas of the clivus were generally smaller in size at presentation and patients with sacral chordomas had more metastases and more often recurrent disease...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28487406/set1a-compass-and-shadow-enhancers-in-the-regulation-of-homeotic-gene-expression
#6
Kaixiang Cao, Clayton K Collings, Stacy A Marshall, Marc A Morgan, Emily J Rendleman, Lu Wang, Christie C Sze, Tianjiao Sun, Elizabeth T Bartom, Ali Shilatifard
The homeotic (Hox) genes are highly conserved in metazoans, where they are required for various processes in development, and misregulation of their expression is associated with human cancer. In the developing embryo, Hox genes are activated sequentially in time and space according to their genomic position within Hox gene clusters. Accumulating evidence implicates both enhancer elements and noncoding RNAs in controlling this spatiotemporal expression of Hox genes, but disentangling their relative contributions is challenging...
May 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28484075/twist1-wdr5-hottip-regulates-hoxa9-chromatin-to-facilitate-prostate-cancer%C3%A2-metastasis
#7
Reem Malek, Rajendra P Gajula, Russell D Williams, Belinda Nghiem, Brian W Simons, Katriana Nugent, Hailun Wang, Kekoa Taparra, Ghali Lemtiri-Chlieh, Arum R Yoon, Lawrence True, Steven S An, Theodore L DeWeese, Ashley E Ross, Edward M Schaeffer, Kenneth J Pienta, Paula J Hurley, Colm Morrissey, Phuoc T Tran
TWIST1 is a transcription factor critical for development which can promote prostate cancer metastasis. During embryonic development, TWIST1 and HOXA9 are co-expressed in mouse prostate and then silenced post-natally. Here we report that TWIST1 and HOXA9 co-expression are re-activated in mouse and human primary prostate tumors and are further enriched in human metastases, correlating with survival. TWIST1 formed a complex with WDR5 and the lncRNA Hottip/HOTTIP, members of the MLL/COMPASS-like H3K4 methylases, which regulate chromatin in the Hox/HOX cluster during development...
May 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28476883/the-long-non-coding-rna-hotair-enhances-pancreatic-cancer-resistance-to-tnf-related-apoptosis-inducing-ligand
#8
Shan-Zhong Yang, Fei Xu, Tong Zhou, Xinyang Zhao, Jay M McDonald, Yabing Chen
Pancreatic cancer is a malignant neoplasm with a high mortality rate. Therapeutic agents that activate TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis have shown promising efficacy, but many pancreatic cancers are resistant to TRAIL therapy. Epigenetic regulation plays important roles in tumor pathogenesis and resistance, and a recent study indicated that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is overexpressed in pancreatic cancer. However, the role of HOTAIR in pancreatic cancer resistance to anticancer agents is unknown...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28468905/pervasive-behavioural-effects-of-microrna-regulation-in-drosophila
#9
Joao Picao-Osorio, Ines Lago-Baldaia, Pedro Patraquim, Claudio R Alonso
The effects of microRNA (miRNA) regulation on the genetic programs underlying behaviour remain largely unexplored. Despite this, recent work in Drosophila shows that mutation of a single miRNA locus (miR-iab4/iab8) affects the capacity of the larva to correct its orientation if turned upside-down (self-righting, SR) suggesting that other miRNAs might also be involved in behavioural control. Here we explore this possibility studying early larval SR behaviour in a collection of eighty-one Drosophila miRNA mutants covering almost the entire miRNA complement of the late embryo...
May 3, 2017: Genetics
https://www.readbyqxmd.com/read/28464221/overexpression-of-hoxa4-and-hoxa9-genes-promotes-self-renewal-and-contributes-to-colon-cancer-stem-cell-overpopulation
#10
Seema Bhatlekar, Vignesh Viswanathan, Jeremy Z Fields, Bruce M Boman
Because HOX genes encode master regulatory transcription factors that regulate stem cells (SCs) during development and aberrant expression of HOX genes occurs in various cancers, our goal was to determine if dysregulation of HOX genes is involved in the SC origin of colorectal cancer (CRC). We previously reported that HOXA4 and HOXD10 are expressed in the colonic SC niche and are overexpressed in CRC. HOX gene expression was studied in SCs from human colon tissue and CRC cells (CSCs) using qPCR and immunostaining...
May 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28462489/role-of-maml1-and-meis1-in-esophageal-squamous-cell-carcinoma-depth-of-invasion
#11
Mohammad Reza Abbaszadegan, Meysam Moghbeli
Homeobox (HOX) transcription factors and NOTCH signaling pathway are critical regulators of stem cell functions, cell fate in development and homeostasis of gastrointestinal tissues. In the present study, we analyzed cross talk between NOTCH pathway and HOX genes through assessment of probable correlation betweenMAML1 and MEIS1 as the main transcription factor of NOTCH pathway and enhancer of HOX transcriptional machinery, respectively in esophageal squamous cell carcinoma (ESCC) patients. Fifty one ESCC cases were enrolled to assess the levels of Meis1 and Maml1 mRNA expression using real-time polymerase chain reaction (PCR)...
May 1, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28456906/the-epigenomic-landscape-in-osteoarthritis
#12
REVIEW
Tommie C Simon, Matlock A Jeffries
PURPOSE OF REVIEW: Epigenomics has emerged as a key player in our rapidly evolving understanding of osteoarthritis. Historical studies implicated epigenetic alterations, particularly DNA methylation, in OA pathogenesis; however, recent technological advances have resulted in numerous epigenome-wide studies examining in detail epigenetic modifications in OA. The purpose of this article is to introduce basic concepts in epigenetics and their recent applications to the study of osteoarthritis development and progression...
June 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28445933/the-long-noncoding-rna-hotair-promotes-parkinson-s-disease-by-upregulating-lrrk2-expression
#13
Sheng Wang, Xuan Zhang, Yuanyuan Guo, Han Rong, Tiebang Liu
Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes. HOTAIR (Hox transcript antisense intergenic RNA), an approximately 2.2 kb long noncoding RNA transcribed from the HOXC locus, is upregulated in various diseases. However, the role of HOTAIR in Parkinson's disease (PD) remains unclear. A mouse model of PD was developed by intraperitoneal injection of MPTP. The expression of HOTAIR and LRRK2 were detected in the PD mice and in human neuroblastoma cell lines SH-SY5Y pretreated with MPP+...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423671/genome-wide-dna-methylation-analysis-reveals-molecular-subtypes-of-pancreatic-cancer
#14
Nitish Kumar Mishra, Chittibabu Guda
Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States with a five-year patient survival rate of only 6%. Early detection and treatment of this disease is hampered due to lack of reliable diagnostic and prognostic markers. Recent studies have shown that dynamic changes in the global DNA methylation and gene expression patterns play key roles in the PC development; hence, provide valuable insights for better understanding the initiation and progression of PC. In the current study, we used DNA methylation, gene expression, copy number, mutational and clinical data from pancreatic patients...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423659/targeting-hox-pbx-dimers-in-cancer
#15
REVIEW
Richard Morgan, Mohamed El-Tanani, Keith D Hunter, Kevin J Harrington, Hardev S Pandha
The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415631/lncrna-hotair-acts-a-competing-endogenous-rna-to-control-the-expression-of-notch3-via-sponging-mir-613-in-pancreatic-cancer
#16
Huihua Cai, Jie Yao, Yong An, Xuemin Chen, Weibo Chen, Di Wu, Boyang Luo, Yong Yang, Yong Jiang, Donglin Sun, Xiaozhou He
Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404743/nuclear-complex-of-glyceraldehyde-3-phosphate-dehydrogenase-and-dna-repair-enzyme-apurinic-apyrimidinic-endonuclease-i-protect-smooth-muscle-cells-against-oxidant-induced-cell-death
#17
Xuwei Hou, Patricia Snarski, Yusuke Higashi, Tadashi Yoshida, Alexander Jurkevich, Patrick Delafontaine, Sergiy Sukhanov
Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMC that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated H2O2-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis...
April 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28402266/expression-signatures-of-hox-cluster-genes-in-cervical-cancer-pathogenesis-impact-of-human-papillomavirus-type-16-oncoprotein-e7
#18
Sweta Sharma Saha, Rahul Roy Chowdhury, Nidhu Ranjan Mondal, Sudipta Roy, Sharmila Sengupta
The Homeobox (HOX) genes encode important transcription factors showing deregulated expression in several cancers. However, their role in cervical cancer pathogenesis, remains largely unexplored. Herein, we studied their association with Human Papillomavirus type 16 (HPV16) mediated cervical cancers. Our previously published gene expression microarray data revealed a significant alteration of 12 out of 39 HOX cluster members among cervical cancer cases, in comparison to the histopathologically normal controls...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399410/hoxa9-and-meis1-cooperatively-induce-addiction-to-syk-signaling-by-suppressing-mir-146a-in-acute-myeloid-leukemia
#19
Sebastian Mohr, Carmen Doebele, Federico Comoglio, Tobias Berg, Julia Beck, Hanibal Bohnenberger, Gabriela Alexe, Jasmin Corso, Philipp Ströbel, Astrid Wachter, Tim Beissbarth, Frank Schnütgen, Anjali Cremer, Nadine Haetscher, Stefanie Göllner, Arefeh Rouhi, Lars Palmqvist, Michael A Rieger, Timm Schroeder, Halvard Bönig, Carsten Müller-Tidow, Florian Kuchenbauer, Ekkehard Schütz, Anthony R Green, Henning Urlaub, Kimberly Stegmaier, R Keith Humphries, Hubert Serve, Thomas Oellerich
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28399140/collinear-hox-hox-interactions-are-involved-in-patterning-the-vertebrate-anteroposterior-a-p-axis
#20
Kongju Zhu, Herman P Spaink, Antony J Durston
Investigating regulation and function of the Hox genes, key regulators of positional identity in the embryo, opened a new vista in developmental biology. One of their most striking features is collinearity: the temporal and spatial orders of expression of these clustered genes each match their 3' to 5' order on the chromosome. Despite recent progress, the mechanisms underlying collinearity are not understood. Here we show that ectopic expression of 4 different single Hox genes predictably induces and represses expression of others, leading to development of different predictable specific sections of the body axis...
2017: PloS One
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