HOXB5 Cooperates with NKX2-1 in the Transcription of Human RET

Zhu, Joe Jiang; Garcia-Barcelo, Maria-Mercedes; Tam, Paul Kwong Hang; Lui, Vincent Chi Hang

doi:10.1371/journal.pone.0020815

Cited by 24 publications

(28 citation statements)

References 35 publications

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“…HoxB5 binds to the Hox consensus sequence upstream of transcription start of Ret gene (glial cell line-derived neurotrophic factor [GDNF]-RET pathway) and that deletion of the binding sequence of Hoxb5 abolishes its trans-activation of RET gene in studies related to enteric nervous system. 42 Therefore, in the context of kidney development, expression differences in Hoxb5 and regulation of Ret (by Hoxb5) could lead to dysregulation of GDNF-RET pathway and alter kidney development. Second, Smoc2 (SPARC-related modular calcium binding 2) proteins are thought to influence growth factor signaling, migration, proliferation, and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Wang¹,

Johnson²,

White³

et al. 2015

Journal of the American Society of Nephrology

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Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney.

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Section: Discussionmentioning

confidence: 99%

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Wang¹,

Johnson²,

White³

et al. 2015

Journal of the American Society of Nephrology

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“…PCR products spanning the putative HOXbinding sites of the human SOX9 promoter were labeled with Biotin-11-UTP (Pierce, Thermo Fisher Scientific, Rockland, MA, USA), EMSA was performed as previously described. 46 ChIP and quantitative PCR assay. ChIP assay on human neuroblastoma cell line SK-N-SH (#HTB-11) (ATCC, Manassas, VA, USA) transfected with HOXB5 or Flag-enb5 was performed as previously described.…”

Section: Discussionmentioning

confidence: 99%

“…ChIP assay on human neuroblastoma cell line SK-N-SH (#HTB-11) (ATCC, Manassas, VA, USA) transfected with HOXB5 or Flag-enb5 was performed as previously described. 46 ChIP assay on mouse developing CNS was performed with head and NT tissues from 27 E9.5 WT mouse embryos with minor modifications. 46,47 See Supplementary Information for quantitative PCR primers for human and mouse Sox9 promoters.…”

Section: Discussionmentioning

confidence: 99%

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Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice

et al. 2013

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Neural crest cells (NCCs) migrate from different regions along the anterior-posterior axis of the neural tube (NT) to form different structures. Defective NCC development causes congenital neurocristopathies affecting multiple NCC-derived tissues in human. Perturbed Hoxb5 signaling in vagal NCC causes enteric nervous system (ENS) defects. This study aims to further investigate if perturbed Hoxb5 signaling in trunk NCC contributes to defects of other NCC-derived tissues besides the ENS. We perturbed Hoxb5 signaling in NCC from the entire NT, and investigated its impact in the development of tissues derived from these cells in mice. Perturbation of Hoxb5 signaling in these NCC resulted in Sox9 downregulation, NCC apoptosis, hypoplastic sympathetic and dorsal root ganglia, hypopigmentation and ENS defects. Mutant mice with NCC-specific Sox9 deletion also displayed some of these phenotypes. In vitro and in vivo assays indicated that the Sox9 promoter was bound and trans-activated by Hoxb5. In ovo studies further revealed that Sox9 alleviated apoptosis induced by perturbed Hoxb5 signaling, and Hoxb5 induced ectopic Sox9 expression in chick NT. This study demonstrates that Hoxb5 regulates Sox9 expression in NCC and disruption of this signaling causes Sox9 downregulation, NCC apoptosis and multiple NCC-developmental defects. Phenotypes such as ENS deficiency, hypopigmentation and some of the neurological defects are reported in patients with Hirschsprung disease (HSCR). Whether dysregulation of Hoxb5 signaling and early depletion of NCC contribute to ENS defect and other neurocristopathies in HSCR patients deserves further investigation.

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“…유방암의 경우 조직과 세포에서 HOX 유전자 전체의 발현 양상을 비교해 보았을 때, 다양한 HOX 유전자들의 발현이 악성과 비악성에서 차이가 있음 이 보고되었다 (Hur et al, 2014). 특히 혈관 (Fessner et al, 2014), 장 (Zhu et al, 2011) 그리고 신경능 (Kam et al, 2014) 발달에 있어서 중요한 역할을 한다고 알려진 HOXB5는 위 (Hong et al, 2015), 폐 (Zhang et al, 2017), 식도 (Sun et al, 2016) 등에서 종양의 진행과 전이에서의 중요성이 알려져 있으며, 유방암 조직에서 그 발현량이 정상 조직에 비하 여 증가되어 있다. 특히 증가된 HOXB5는 세포증식, 암 의 침습성, 상피간엽이행(epithelial-mesenchymal transition, EMT), Tamoxifen 저항성을 나타내는데 기여한다는 것이 알려져 있다 (Lee et al, 2015).…”

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HOXB5 Directly Regulates the Expression of IL-6 in MCF7 Breast Cancer Cells

Kim

Lee

Kim

2017

BSL

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HOX genes are transcription factors that play important roles in body patterning and cell fate specification during normal development. In previous study, we found aberrant overexpression of HOXB5 in breast cancer tissues and cell lines, and demonstrated that HOXB5 is important in regulation of cell proliferation, tamoxifen resistance, and invasiveness through the epithelial-mesenchymal transition (EMT). Although the relationship between HOXB5 and phenotypic changes in MCF7 breast cancer cells has been studied, the molecular function of HOXB5 as a transcription factor remains unclear. IL-6 has been reported to be involved in not only inflammation but also cancer progression, which is characterized by the increase of growth speed and invasiveness of tumor cells. In this study, we selected Interleukin-6 (IL-6) as HOXB5 putative downstream target gene and discovered that HOXB5 transcriptionally up-regulated the expression of IL-6 in HOXB5 overexpressing MCF7 cells. The upstream region (~1.2 kb) of IL-6 promoter turned out to contain several putative HOX consensus binding sites. Chromatin immunoprecipitation assay confirmed that HOXB5 directly binds to the promoter region of IL-6 and positively regulated the expression of IL-6. These data all together, indicate that HOXB5 promotes IL-6 transcription by actively binding to the putative binding sites located in the upstream region of IL-6, which enable to increase its promoter activity in MCF7 breast cancer cells.

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HOXB5 Cooperates with NKX2-1 in the Transcription of Human RET

Cited by 24 publications

References 35 publications

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Perturbation of Hoxb5 signaling in vagal and trunk neural crest cells causes apoptosis and neurocristopathies in mice

HOXB5 Directly Regulates the Expression of IL-6 in MCF7 Breast Cancer Cells

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