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Hox regulation

Francesca Salamanna, Simona Cepollaro, Deyanira Contartese, Gianluca Giavaresi, Giovanni Barbanti Brodano, Cristiana Griffoni, Alessandro Gasbarrini, Milena Fini
STUDY DESIGN: Laboratory study. OBJECTIVE: Mesenchymal stem cells (MSCs) derived from whole bone marrow aspirate (BMA) and MSCs derived from density-gradient centrifugation were isolated from vertebral bodies and cultured under either hypoxic or normoxic conditions to evaluate their biological characteristics and HOX and TALE signature able to improve spinal surgery procedures. SUMMARY OF BACKGROUND DATA: The use of spinal fusion procedures has increased over the last decades; however, failed fusion still remains an important problem...
March 15, 2018: Spine
Sigrun Schmähling, Arno Meiler, Yoonjung Lee, Arif Mohammed, Katja Finkl, Katharina Tauscher, Lars Israel, Marc Borath, Julia Philippou-Massier, Helmut Blum, Bianca Habermann, Axel Imhof, Ji-Joon Song, Jürg Müller
The Drosophila Ash1 protein is a trithorax-group (trxG) regulator that antagonizes Polycomb repression at HOX genes. Ash1 di-methylates lysine 36 in histone H3 (H3K36me2) but how this activity is controlled and at which genes it functions is not well understood. We show that Ash1 protein purified from Drosophila exists in a complex with MRG15 and Caf1 that we named AMC. In Drosophila and human AMC, MRG15 binds a conserved FxLP motif near the Ash1 SET domain and stimulates H3K36 di-methylation on nucleosomes...
March 14, 2018: Development
Shanshan Sun, Yansheng Wu, Wenyu Guo, Feng Yu, Lingping Kong, Yu Ren, Yu Wang, Xiaofeng Yao, Chao Jing, Chao Zhang, Mingyang Liu, Yuqing Zhang, Minghui Zhao, Zhaoqing Li, Chuanqiang Wu, Yu Qiao, Jingxuan Yang, Xudong Wang, Lun Zhang, Min Li, Xuan Zhou
PURPOSE: Phosphotidylinositol-3-kinase (PI3K)and signal transducers and activators of transcription 3 (STAT3) are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate HNSCC growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of head and neck squamous cell cancer (HNSCC). In this study, we attempted to establish the correlation of PI3K-STAT3-HOTAIR signaling with the progression of HNSCC and its sensitivity towards platinum-based and targeted anti-EGFR combination therapy...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Lyndsay G Selland, Sophie Koch, Malcolm Laraque, Andrew J Waskiewicz
The vertebrate hindbrain is composed of a series of lineage-restricted segments termed rhombomeres. Segment-specific gene expression drives unique programs of neuronal differentiation. Two critical embryonic signaling pathways, Fibroblast Growth Factor (FGF) and Retinoic Acid (RA), regulate early embryonic rhombomere patterning. The earliest expressed hox genes, hoxb1b and hoxb1a in zebrafish, are logical candidates for establishing signaling networks that specify segmental identity. We sought to determine the mechanism by which hox genes regulate hindbrain patterning in zebrafish...
February 26, 2018: Mechanisms of Development
Mette Handberg-Thorsager, Juliana Gutierrez-Mazariegos, Stefan T Arold, Eswar Kumar Nadendla, Paola Y Bertucci, Pierre Germain, Pavel Tomançak, Keely Pierzchalski, Jace W Jones, Ricard Albalat, Maureen A Kane, William Bourguet, Vincent Laudet, Detlev Arendt, Michael Schubert
Retinoic acid (RA) is an important intercellular signaling molecule in vertebrate development, with a well-established role in the regulation of hox genes during hindbrain patterning and in neurogenesis. However, the evolutionary origin of the RA signaling pathway remains elusive. To elucidate the evolution of the RA signaling system, we characterized RA metabolism and signaling in the marine annelid Platynereis dumerilii , a powerful model for evolution, development, and neurobiology. Binding assays and crystal structure analyses show that the annelid retinoic acid receptor (RAR) binds RA and activates transcription just as vertebrate RARs, yet with a different ligand-binding pocket and lower binding affinity, suggesting a permissive rather than instructive role of RA signaling...
February 2018: Science Advances
Amandine Draime, Laure Bridoux, Magali Belpaire, Tamara Pringels, Janne Tys, René Rezsohazy
Understanding how the activity of transcription factors like HOX proteins is regulated remains a widely open question. In a recent screen for proteins interacting with HOXA1, we identified a PRDM protein family member, PRDM14, which is known to be transiently co-expressed with HOXA1 in epiblast cells before their specification towards somatic versus germ cell fate. Here, we confirm PRDM14 is an interactor of HOXA1 and we identify the homeodomain of HOXA1 as well as the PR domain and Zinc fingers of PRDM14 to be required for the interaction...
February 19, 2018: Biochimica et Biophysica Acta
Elżbieta Pawłowska, Joanna Szczepanska, Janusz Blasiak
HOTAIR (HOX transcript antisense RNA) plays a critical role in chromatin dynamics through the interaction with histone modifiers resulting in transcriptional gene silencing. The promoter of the HOTAIR gene contains multiple estrogen response elements (EREs) and is transcriptionally activated by estradiol in estrogen receptor-positive breast cancer cells. HOTAIR competes with BRCA1, a critical protein in breast cancer and is a critical regulator of genes involved in epithelial-to-mesenchymal transition. It mediates an oncogenic action of c-Myc, essential for breast carcinogenesis...
November 3, 2017: International Journal of Molecular Sciences
Yun-Xiao Zhou, Chuan Wang, Li-Wei Mao, Yan-Li Wang, Li-Qun Xia, Wei Zhao, Jie Shen, Jun Chen
Background LncRNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been confirmed to involve in the tumorigenic progression of endometrial carcinoma (EC). However, the molecular mechanism of HOTAIR in EC are not fully elucidated. Methods The expression of HOTAIR and miR-646 in human EC tissues was determined by qRT-PCR. The effect of miR-646 on EC cells was assessed by the cell viability, migration and invasion using CCK-8 assays and transwell assays. RIP assays and RNA pull-down assays were performed to explore the interaction between HOTAIR and miR-646...
February 21, 2018: American Journal of Physiology. Cell Physiology
Siwei Liu, Huajiang Lei, Fangyuan Luo, Yilin Li, Lan Xie
This study aimed at investigating the biological functions of long non-coding RNAs (lncRNAs) hox transcript antisense intergenic RNA (HOTAIR) in resistant ovarian cancer cells, exploring the regulation effect of HOTAIR on HOXA7, and investigating their influence on the chemosensitivity of ovarian cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for the verification of HOTAIR expression in resistant and sensitive groups. How HOTAIR downregulation affected cell proliferation, migration and invasion, and apoptosis were determined using the MTT assay and the colony formation assay, the Transwell assay and flow cytometry analysis, respectively...
February 19, 2018: Biological Chemistry
Satyanarayan Rao, Tsu-Pei Chiu, Judith F Kribelbauer, Richard S Mann, Harmen J Bussemaker, Remo Rohs
BACKGROUND: DNA shape analysis has demonstrated the potential to reveal structure-based mechanisms of protein-DNA binding. However, information about the influence of chemical modification of DNA is limited. Cytosine methylation, the most frequent modification, represents the addition of a methyl group at the major groove edge of the cytosine base. In mammalian genomes, cytosine methylation most frequently occurs at CpG dinucleotides. In addition to changing the chemical signature of C/G base pairs, cytosine methylation can affect DNA structure...
February 6, 2018: Epigenetics & Chromatin
Xiankuan Xie, Yuxiang Xiao, Xin Huang
Aim: Homeobox (HOX) genes and their protein products have been found to function as oncogenes in the progression of many cancers. But the role of Homeobox C10 (HOXC10) in osteosarcoma (OS) still remains less understood. In this study, we firstly determine the biologic functions of HOXC10 in OS. Materials and methods: We examined the expression of HOXC10 in OS tissues by quantitative real-time polymerase chain reaction and Western blot assays. We investigated the effects of HOXC10 on cell proliferation, apoptosis and caspase 3 activity in three OS cell lines by RNA interference, Cell Counting Kit-8, flow cytometry and colorimetric assays...
2018: OncoTargets and Therapy
Yasuyuki Fujisaka, Tomoaki Iwata, Keiichi Tamai, Mao Nakamura, Mai Mochizuki, Rie Shibuya, Kazunori Yamaguchi, Tooru Shimosegawa, Kennichi Satoh
Accumulating evidence demonstrated that Hox antisense intergenic RNA (HOTAIR) serves essential roles in the development and metastasis of several types of cancer. In hepatocellular carcinoma (HCC), high expression of HOTAIR is associated with poor prognosis, and HOTAIR regulates cell migration and proliferation. However, the downstream molecular targets of HOTAIR depend on the cancer cell types, and little is known about the precise molecular mechanisms of HOTAIR involved in cancer development. The present study investigated the role of HOTAIR in HCC cell lines...
January 2018: Oncology Letters
Michaela Edmond, Olivia Hanley, Polyxeni Philippidou
Vital motor functions, such as respiration and locomotion, rely on the ability of spinal motor neurons (MNs) to acquire stereotypical positions in the ventral spinal cord and to project with high precision to their peripheral targets. These key properties of MNs emerge during development through transcriptional programs that dictate their subtype identity and connectivity; however, the molecular mechanisms that establish the transcriptional landscape necessary for MN specification are not fully understood. Here, we show that the enzyme topoisomerase IIβ (Top2β) controls MN migration and connectivity...
November 2017: ENeuro
Yin Tang, Lan Zhang, Tianchi Tu, Yijia Li, Dana Murray, Qisheng Tu, Jake Jinkun Chen
Skeletal tissue originates from mesenchymal stem cells (MSCs) with differentiation potential into the osteoblast lineage regulated by essential transcriptional and post-transcriptional mechanisms. Recently, miRNAs and histone modifications have been identified as novel key regulators of osteogenic differentiation of MSCs. Here, we identified miR-99a and its target lysine (K)-specific demethylase 6B (KDM6B) gene as novel modulators of osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Microarray profiling and further validation by quantitative real-time RT-PCR revealed that miR-99a was up-regulated during osteoblastic differentiation of BMSCs, and decreased in differentiated osteoblasts...
January 29, 2018: Journal of Cellular and Molecular Medicine
Houli Liu, Mingsheng Zhang, Shanshan Xu, Jie Zhang, Jin Zou, Chenchen Yang, Yang Zhang, Chen Gong, Yuanzhong Kai, Yong Li
Homeobox (HOX) genes encode a family of transcription factors, which play crucial roles in numerous processes, and their dysregulation is involved in the carcinogenesis of many human cancers. In the present study, we investigated the roles of HOXC8 in non-small cell lung cancer (NSCLC). We showed that HOXC8 was upregulated in clinical NSCLC specimens compared to normal lung tissues, and the high expression of HOXC8 correlated with tumor node metastasis (TNM) stage, tumor status, lymph nodal status and poor relapse-free survival for lung cancer patients...
January 17, 2018: Oncogenesis
Jeramiah J Smith, Nataliya Timoshevskaya, Chengxi Ye, Carson Holt, Melissa C Keinath, Hugo J Parker, Malcolm E Cook, Jon E Hess, Shawn R Narum, Francesco Lamanna, Henrik Kaessmann, Vladimir A Timoshevskiy, Courtney K M Waterbury, Cody Saraceno, Leanne M Wiedemann, Sofia M C Robb, Carl Baker, Evan E Eichler, Dorit Hockman, Tatjana Sauka-Spengler, Mark Yandell, Robb Krumlauf, Greg Elgar, Chris T Amemiya
The sea lamprey (Petromyzon marinus) serves as a comparative model for reconstructing vertebrate evolution. To enable more informed analyses, we developed a new assembly of the lamprey germline genome that integrates several complementary data sets. Analysis of this highly contiguous (chromosome-scale) assembly shows that both chromosomal and whole-genome duplications have played significant roles in the evolution of ancestral vertebrate and lamprey genomes, including chromosomes that carry the six lamprey HOX clusters...
January 22, 2018: Nature Genetics
Zahida Yesmin Roly, Brendan Backhouse, Andrew Cutting, Tiong Yang Tan, Andrew H Sinclair, Katie L Ayers, Andrew T Major, Craig A Smith
The Müllerian ducts are part of the embryonic urogenital system. They give rise to mature structures that serve a critical function in the transport and development of the oocyte and/or embryo. In most vertebrates, both sexes initially develop Müllerian ducts during embryogenesis, but they regress in males under the influence of testis-derived Anti-Müllerian Hormone (AMH). A number of regulatory factors have been shown to be essential for proper duct development, including Bmp and Wnt signaling molecules, together with homeodomain transcription factors such as PAX2 and LIM1...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
Mingzhu Liu, Jinying Jia, Xinjie Wang, Yanjie Liu, Chunfang Wang
BACKGROUND: HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) widely involved in the progression of numerous malignancies. Whereas, the potential molecular mechanism of HOTAIR involved in cervical cancer progression is still needed to be elaborated. METHODS: The expression of HOTAIR and miR-143-3p were detected in cervical cancer tissues and cells by qRT-PCR. MTT and flow cytometry analysis were performed to measure cell proliferation and apoptosis...
January 16, 2018: Cancer Biology & Therapy
Guan Sun, Yingyi Wang, Junxia Zhang, Ning Lin, Yongping You
Among the malignant tumors of the human central nervous system, gliomas have the highest incidence and recurrence rate. Therefore, exploration of the molecular mechanism that underlies the development and progression of gliomas is of great clinical significance. Many studies have demonstrated that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the development and progression of tumors. In the present study, both an RNAhybrid analysis and a dual-luciferase reporter gene assay confirmed that microRNA-15b (miR-15b) binding sites were present in the sequence of HOX transcript antisense RNA (HOTAIR)...
January 11, 2018: Journal of Cellular Biochemistry
Liang Liu, Sitong Cui, Teng Wan, Xiaojian Li, Wei Tian, Rui Zhang, Liangsheng Luo, Yan Shi
LncRNA HOX transcript antisense intergenic RNA (HOTAIR) has been shown to play prominent roles in tumorigenesis. However, its precise molecular mechanism in glioma has not been completely elucidated. In this study, we found that HOTAIR was aberrantly up-regulated in glioma tissues and was negatively correlated with miR-126-5p expression. Next, we determined that HOTAIR promote glioma progression by sponging miR-126-5p. Subsequently, glutaminase (GLS) was confirmed to be a direct target of miR-126-5p using bioinformatics software and a luciferase reporter assay...
January 10, 2018: Journal of Cellular Physiology
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