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Jinping Guan, Zimin Liu, Menjing Xiao, Fengyun Hao, Chenghong Wang, Yan Chen, Yingying Lu, Jun Liang
BACKGROUND AND OBJECTIVE: MicroRNAs play an important role in cell proliferation, apoptosis, differentiation, and invasion by regulating the expression of various genes. For example, the downregulation of microRNA-199a-3p (miR-199a-3p) that is noted in numerous human malignancies, including hepatocellular carcinoma (HCC), results in a poor prognosis in patients with HCC. This finding suggests that miR-199a-3p overexpression in HCC could provide a new treatment approach. We explored this possibility by examining the effects of miR-199a-3p on the growth and apoptosis of HCC cells in vitro and vivo...
2017: American Journal of Translational Research
Ryuk-Jun Kwon, Myoung-Eun Han, Youn-Jae Kim, Yun Hak Kim, Ji-Young Kim, Liangwen Liu, Woong Heo, Sae-Ock Oh
Zinc-fingers and homeoboxes 1 (ZHX1) is a nuclear transcription repressor and known to be involved in cell differentiation and tumorigenesis. However, the pathophysiological roles of ZHX1 have not been characterized in glioblastoma. We examined ZHX1 expression in glioblastoma patients' tissues and analyzed overall survival of the patients based on expression level of ZHX1. We also examined the effects of ZHX1 on proliferation and motility of glioblastoma cells. In silico analysis and immunohistochemical studies showed that the messenger RNA and protein expressions of ZHX1 were higher in the tissues of glioblastoma patients than in normal brain tissues, and that its overexpression was associated with reduced survival...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ryuk-Jun Kwon, Yun Hak Kim, Dae Cheon Jeong, Myoung-Eun Han, Ji-Young Kim, Liangwen Liu, Jin-Sup Jung, Sae-Ock Oh
Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage...
2017: PloS One
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
To identify novel cancer-related genes targeted by copy number alterations, we performed genomic profiling of T-cell acute lymphoblastic leukemia (T-ALL) cell lines. In 3/8, we identified a shared deletion at chromosomal position 2p16.3-p21. Within the minimally deleted region, we recognized several candidate tumor suppressor (TS) genes, including FBXO11 and FOXN2. An additional deletion at chromosome 14q23.2-q32.11 included FOXN3, highlighting this class of FOX genes as potential TS. Quantitative expression analyses of FBXO11, FOXN2, and FOXN3 confirmed reduced transcript levels in the identified cell lines...
September 2017: Leukemia & Lymphoma
Ryuk-Jun Kwon, Myoung-Eun Han, Ji-Young Kim, Liangwen Liu, Yun-Hak Kim, Jin-Sup Jung, Sae-Ock Oh
Zinc-fingers and homeoboxes 1 (ZHX1) is a transcription repressor that has been associated with the progressions of hepatocellular carcinoma, gastric cancer, and breast cancer. However, the functional roles of ZHX1 in cholangiocarcinoma (CCA) have not been determined. We investigated the expression and roles of ZHX1 during the proliferation, migration, and invasion of CCA cells. In silico analysis and immunohistochemical studies showed amplification and overexpression of ZHX1 in CCA tissues. Furthermore, ZHX1 knockdown using specific siRNAs decreased CCA cell proliferation, migration, and invasion, whereas ZHX1 overexpression promoted all three characteristics...
2016: PloS One
Isabelle Chang, Marta Parrilla
Homeodomain proteins are encoded by homeobox genes and regulate development and differentiation in many neuronal systems. The mouse vomeronasal organ (VNO) generates in situ mature chemosensory neurons from stem cells. The roles of homeodomain proteins in neuronal differentiation in the VNO are poorly understood. Here we have characterized the expression patterns of 28 homeobox genes in the VNO of C57BL/6 mice at postnatal stages using multicolor fluorescent in situ hybridization. We identified 11 homeobox genes (Dlx3, Dlx4, Emx2, Lhx2, Meis1, Pbx3, Pknox2, Pou6f1, Tshz2, Zhx1, Zhx3) that were expressed exclusively in neurons; 4 homeobox genes (Pax6, Six1, Tgif1, Zfhx3) that were expressed in all non-neuronal cell populations, with Pax6, Six1 and Tgif1 also expressed in some neuronal progenitors and precursors; 12 homeobox genes (Adnp, Cux1, Dlx5, Dlx6, Meis2, Pbx2, Pknox1, Pou2f1, Satb1, Tshz1, Tshz3, Zhx2) with expression in both neuronal and non-neuronal cell populations; and one homeobox gene (Hopx) that was exclusively expressed in the non-sensory epithelium...
July 2016: Gene Expression Patterns: GEP
Xingjie Ma, Minlu Huang, Zhenqiang Wang, Bingya Liu, Zhenggang Zhu, Chen Li
Zinc-fingers and homeoboxes 1 (ZHX1) was implicated in the carcinogenesis of human cancers. However, little is known about the role of ZHX1 in gastric cancer (GC). Here, we found that ZHX1 was downregulated in GC tissues compared with paired non-tumor tissues and loss of ZHX1 expression correlated with aggressive clinical characteristics of GC patients. ZHX1 induced G1/S arrest by decreasing cyclin D1 and cyclin E expression, and induced cell apoptosis by Bcl2 downregulation and Bax and cleaved Caspase-3 upregulation...
2016: Journal of Cancer
Chih-Ping Chen, Ming-Huei Lin, Yi-Yung Chen, Schu-Rern Chern, Yen-Ni Chen, Peih-Shan Wu, Chen-Wen Pan, Meng-Shan Lee, Wayseen Wang
OBJECTIVE: The aim of this research was to present prenatal diagnosis of Langer-Giedion syndrome (LGS/TRPS type II) and Cornelia de Lange syndrome-4 (CDLS4). MATERIALS AND METHODS: A 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis of amniocentesis revealed an interstitial deletion of chromosome 8q or del(8)(q23.3q24.13). Level II prenatal ultrasound examination revealed craniofacial dysmorphism...
October 2015: Taiwanese Journal of Obstetrics & Gynecology
Stefan Nagel, Stefan Ehrentraut, Corinna Meyer, Maren Kaufmann, Hans G Drexler, Roderick A F MacLeod
In Hodgkin lymphoma (HL) we recently reported that deregulated homeobox gene MSX1 mediates repression of the B-cell specific transcription factor ZHX2. In this study we investigated regulation of MSX1 in this B-cell malignancy. Accordingly, we analyzed expression and function of OTX homeobox genes which activate MSX1 transcription during embryonal development in the neural plate border region. Our data demonstrate that OTX1 and OTX2 are aberrantly expressed in both HL patients and cell lines. Moreover, both OTX loci are targeted by genomic gains in overexpressing cell lines...
2015: PloS One
Zhenqiang Wang, Xingjie Ma, Qiang Cai, Xinjing Wang, Beiqin Yu, Qu Cai, Bingya liu, Zhenggang Zhu, Chen Li
Accumulating evidence has indicated that microRNAs (miRNAs) act as critical epigenetic regulators in tumor carcinogenesis. Here, we report that miR-199a-3p was significantly upregulated in gastric cancer (GC) cell lines and tissues. Functional studies demonstrated that miR-199a-3p dramatically increased cell proliferation and suppressed cell apoptosis both in vitro and in vivo. Furthermore, the transcriptional regulator zinc fingers and homeoboxes 1 (ZHX1) was identified as one of the direct downstream targets of miR-199a-3p, miR-199a-3p bound to the ZHX1 3′ untranslated region (3′UTR) to regulate ZHX1 protein expression...
November 28, 2014: FEBS Letters
Xianzhong Xu, Surya V S R K Pulavarti, Alexander Eletsky, Yuanpeng Janet Huang, Thomas B Acton, Rong Xiao, John K Everett, Gaetano T Montelione, Thomas Szyperski
High-quality solution NMR structures of three homeodomains from human proteins ALX4, ZHX1 and CASP8AP2 were solved. These domains were chosen as targets of a biomedical theme project pursued by the Northeast Structural Genomics Consortium. This project focuses on increasing the structural coverage of human proteins associated with cancer.
December 2014: Journal of Structural and Functional Genomics
Jianping Wang, Dejie Liu, Xiaohong Liang, Lifen Gao, Xuetian Yue, Yang Yang, Chunhong Ma, Jun Liu
The zinc-fingers and homeoboxes protein 1 (ZHX1) consists of 873 amino acid residues, is localized in the cell nucleus and appears to act as a transcriptional repressor. Previous studies have shown that ZHX1 interacts with nuclear factor Y subunit α (NF-YA), DNA methyltransferases (DNMT) 3B and ZHX2, all of which are involved in tumorigenesis. However, the exact role of ZHX1 in tumorigenesis remains unknown. The aim of the current study was to construct a recombinant eukaryotic expression plasmid containing the human ZHX1 (hZHX1) gene and to investigate the biological activities of ZHX1 in hepatocellular carcinoma (HCC)...
November 2013: Molecular Medicine Reports
Shuliang Chen, Xiao Yu, Quan Lei, Lixin Ma, Deyin Guo
Zinc-fingers and homeoboxes protein 1 (ZHX1) belongs to the ZF (zinc-fingers) class of homeodomain transcription factors, and its function remains largely unknown. ZHX1 has been previously found to interact with the activation domain of the nuclear factor Y subunit A (NFYA) and to have a transcriptional repression activity. Here, we report that the SUMO-E2 conjugating enzyme Ubc9 was identified to interact with ZHX1 by an interaction screen using a yeast two-hybrid system. This interaction was confirmed by co-immunoprecipitation and co-localization assays...
October 2013: Journal of Cellular Biochemistry
Louise E Bird, Jingshan Ren, Joanne E Nettleship, Gert E Folkers, Raymond J Owens, David K Stammers
BACKGROUND: Zhx1 to 3 (zinc-fingers and homeoboxes) form a set of paralogous genes encoding multi-domain proteins. ZHX proteins consist of two zinc fingers followed by five homeodomains. ZHXs have biological roles in cell cycle control by acting as co-repressors of the transcriptional regulator Nuclear Factor Y. As part of a structural genomics project we have expressed single and multi-domain fragments of the different human ZHX genes for use in structure determination. RESULTS: A total of 30 single and multiple domain ZHX1-3 constructs selected from bioinformatics protocols were screened for soluble expression in E...
May 28, 2010: BMC Structural Biology
Hans Wienk, Ivonne Lammers, Anna Hotze, Jin Wu, Rainer W Wechselberger, Ray Owens, David K Stammers, David Stuart, Robert Kaptein, Gert E Folkers
Binding of the nuclear factor-Y complex (NF-Y) to the inverted CCAAT-box interferes with transcription activation through nucleosome reorganization. The three homologous proteins forming the zinc-fingers and homeoboxes (ZHX) family interact with the activation domain of NF-Ya to repress transcription. Each ZHX-protein contains two generic C2H2 zinc-fingers (ZNF1 and ZNF2) followed by five homeodomains. Although the proteins have been related to the occurrence of certain cancers, the function and structure of the individual ZHX domains are still unknown...
June 2, 2009: Biochemistry
L C Clement, G Liu, I Perez-Torres, Y S Kanwar, C Avila-Casado, S S Chugh
Serial changes in glomerular capillary loop gene expression were used to uncover mechanisms contributing to primary glomerular disease in rat models of passive Heymann nephritis and puromycin nephrosis. Before the onset of proteinuria, podocyte protein-tyrosine phosphatase (GLEPP1) expression was transiently decreased in the nephrosis model, whereas the immune costimulatory molecule B7.1 was stimulated in both models. To relate these changes to the development of proteinuria, the time of onset and intensity of proteinuria were altered...
August 2007: Kidney International
Sung-Hak Kim, Jinah Park, Moon-Chang Choi, Hwang-Phill Kim, Jung-Hyun Park, Yeonjoo Jung, Ju-Hee Lee, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, Tae-You Kim
DNA methyltransferases (DNMT) 3B is a de novo DNMT that represses transcription independent of DNMT activity. In order to gain a better insight into DNMT3B-mediated transcriptional repression, we performed a yeast two-hybrid analysis using DNMT3B as a bait. Of the various binding candidates, ZHX1, a member of zinc-finger and homeobox protein, was found to interact with DNMT3B in vivo and in vitro. N-terminal PWWP domain of DNMT3B was required for its interaction with homeobox motifs of ZHX1. ZHX1 contains nuclear localization signal at C-terminal homeobox motif, and both ZHX1 and DNMT3B were co-localized in nucleus...
April 6, 2007: Biochemical and Biophysical Research Communications
Hiroko Ogata-Kawata, Kazuya Yamada, Miki Uesaka-Yoshino, Norio Kagawa, Kaoru Miyamoto
Corepressor BS69 interacts with ZHX1, a member of the ZHX family having zinc-fingers and homeoboxes. In the rat, we have identified four forms of splicing variants, BS69alpha, BS69beta, BS69gamma, and BS69delta. Based on the amino acid sequence, BS69alpha corresponded to the human orthologue. BS69beta and BS69gamma contain a novel 56 amino acid region encoded by the exon 11b of the rat BS69 gene. Both BS69gamma and BS69delta lacked a region encoded by exon 3 of the gene. Although all four variants were ubiquitously expressed in rats, the transcripts having the exon 11b were detected in mice and rats but not in humans...
2007: Frontiers in Bioscience: a Journal and Virtual Library
Gang Liu, Lionel C Clement, Yashpal S Kanwar, Carmen Avila-Casado, Sumant S Chugh
Transcriptional regulation of podocyte gene expression in primary glomerular disease is poorly understood. In this study, we demonstrate a prominent role of members of the ZHX (zinc fingers and homeoboxes) family of proteins in regulating podocyte gene expression during the development of nephrotic syndrome. While studying mechanisms of glomerular disease, rat ZHX3 was cloned from a down-regulated gene fragment; its cellular localization, DNA binding, and transcriptional repressor properties were characterized; and its ability to influence podocyte gene expression directly or via ZHX1 and ZHX2 was studied...
December 22, 2006: Journal of Biological Chemistry
Zhangfei Shou, Kazuya Yamada, Hiroko Kawata, Osamu Yokoyama, Kaoru Miyamoto
The effect of IL-2 on the expression of the mouse zinc-fingers and homeoboxes 1 (ZHX1) gene was investigated in a mouse cytotoxic T cell line, CTLL-2 cells. IL-2 specifically induced the expression of ZHX1 mRNA. The level of ZHX1 mRNA was decreased in the absence of IL-2. These alterations were in parallel with the status of cell proliferation. The signaling pathways involved in the induction were examined. AG-490, wortmannin, and LY294002 blocked the induction by IL-2. Nuclear run-on assays and a mRNA stability analysis revealed that the half-life of ZHX1 mRNA but not the transcription rate of the gene was increased by IL-2...
February 13, 2004: Biochemical and Biophysical Research Communications
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