Early growth response gene-1 plays a pivotal role in down-regulation of a cohort of genes in uterine leiomyoma

Ishikawa, Hiroshi; Shozu, Makio; Okada, Masahiko; Inukai, Mai; Zhang, Bo; Kato, Keiichi; Kasai, Tokuzo; Inoue, Masakí

doi:10.1677/jme-06-0069

Cited by 12 publications

(9 citation statements)

References 29 publications

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“…2 E ). In agreement with these observations, we found the lung metastasis signature to contain 22% (12/54) of the genes predicted elsewhere to be EGR1 transcriptional targets [31]–[34] and the wound response was previously shown to be coordinated with MYC amplification [35]. In addition, over-representation of an AHR motif is consistent with its association with ER to regulate cell proliferation [36].…”

Section: Resultssupporting

confidence: 85%

Biological Convergence of Cancer Signatures

et al. 2009

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Gene expression profiling has identified cancer prognostic and predictive signatures with superior performance to conventional histopathological or clinical parameters. Consequently, signatures are being incorporated into clinical practice and will soon influence everyday decisions in oncology. However, the slight overlap in the gene identity between signatures for the same cancer type or condition raises questions about their biological and clinical implications. To clarify these issues, better understanding of the molecular properties and possible interactions underlying apparently dissimilar signatures is needed. Here, we evaluated whether the signatures of 24 independent studies are related at the genome, transcriptome or proteome levels. Significant associations were consistently observed across these molecular layers, which suggest the existence of a common cancer cell phenotype. Convergence on cell proliferation and death supports the pivotal involvement of these processes in prognosis, metastasis and treatment response. In addition, functional and molecular associations were identified with the immune response in different cancer types and conditions that complement the contribution of cell proliferation and death. Examination of additional, independent, cancer datasets corroborated our observations. This study proposes a comprehensive strategy for interpreting cancer signatures that reveals common design principles and systems-level properties.

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Section: Resultssupporting

confidence: 85%

Biological Convergence of Cancer Signatures

et al. 2009

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“…TGFβ is known to be dysregulated i.e. increased, in leiomyoma relative to myometrium (39, 40). This increase, in part, could also explain the downregulation of miR-29 seen in leiomyoma.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of microRNA-29 family in leiomyoma contributes to increased major fibrillar collagen production

Marsh

Steinberg

Parker

et al. 2016

Fertility and Sterility

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Objective To determine the expression and function of the microRNA-29 family (miR-29a, 29b, 29c) in human leiomyoma and myometrium. Study Design Basic Science Experimental Design Setting Academic medical center Patients Women undergoing surgery for symptomatic uterine fibroids. Interventions Overexpression and knockdown of miR-29a, 29b, and 29c in primary leiomyoma and myometrial cells. Main outcome measures (1) Expression of the miRNA-29 family members in vivo in leiomyoma versus myometrium; (2) Major fibrillar collagen (I, II, III) expression in leiomyoma and myometrial cells with manipulation of miR-29 species. Results Members of the miR-29 family (29a, 29b, 29c) are all down-regulated in leiomyoma versus myometrium in vivo. The expression of the miR-29 family can be successfully modulated in primary leiomyoma and myometrial cells. Overexpression of the miR-29 family in leiomyoma cells results in down-regulation of the major fibrillar collagens. Down-regulation of the miR-29 species in myometrium results in an increase in collagen type 3 deposition. Conclusions The miR-29 family is consistently down-regulated in leiomyoma compared to matched myometrial tissue. This down-regulation contributes to the increased collagen seen in leiomyomas versus myometrium. When miR-29 members are overexpressed in leiomyoma cells, protein levels of all of the major fibrillar collagens decrease. Mir-29 members are potential therapeutic targets in this highly prevalent condition.

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“…The sheared DNA size was from 600 to 900 bp, with the majority around 800 bp (data not shown). The Egr1 antibody from Santa Cruz Biotechnology was chosen because it has been successfully used in ChIP assays previously (35). Immunoprecipitation of antibody-chromatin complex was performed with protein G-agarose provided in the kit.…”

Section: Methodsmentioning

confidence: 99%

SDF1α/CXCR4 Signaling, via ERKs and the Transcription Factor Egr1, Induces Expression of a 67-kDa Form of Glutamic Acid Decarboxylase in Embryonic Hippocampal Neurons

Luo

Lathia

Mughal

et al. 2008

Journal of Biological Chemistry

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Stromal cell-derived factor ␣ (SDF1␣) and its cognate receptor CXCR4 play an important role in neuronal development in the hippocampus, but the genes directly regulated by SDF1␣/ CXCR4 signaling are unknown. To study the role of CXCR4 targeted genes in neuronal development, we used neuronal cultures established from embryonic day 18 rats. Hippocampal neurons express CXCR4 receptor proteins and are stimulated by SDF1␣ resulting in activation of extracellular signal-regulated kinase (ERK)1/2 and the transcription factor cAMPresponse element-binding protein. SDF1␣ rapidly induces the expression of the early growth response gene Egr1, a transcription factor involved in activity-dependent neuronal responses, in a concentration-dependent manner. Gel-shift analysis showed that SDF1␣ enhances DNA binding activity to the Egr1-containing promoter for GAD67. Chromatin immunoprecipitation analysis using an Egr1 antibody indicated that SDF1␣ stimulation increases binding of Egr1 to a GAD67 promoter DNA sequence. SDF1␣ stimulation increases the expression of GAD67 at both the mRNA and protein levels, and increases the amount and neurite localization of ␥-aminobutyric acid (GABA) in neurons already expressing GABA. SDF1␣-induced Egr1/GAD67 expression is mediated by the G protein-coupled CXCR4 receptor and activation of the ERK pathway. Reduction of Egr1 gene expression using small interfering RNA technology lowers the level of GAD67 transcripts and inhibits SDF1␣-induced GABA production. Inhibition of CXCR4 activation in the developing mouse brain in utero greatly reduced Egr1 and GAD67 mRNA levels and GAD67 protein levels, suggesting a pivotal role for CXCR4 signaling in the development of GABAergic neurons in vivo. Our data suggest that SDF1␣/CXCR4/G protein/ERK signaling induces the expression of the GAD67 system via Egr1 activation, a mechanism that may promote the maturation of GABAergic neurons during development.

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Early growth response gene-1 plays a pivotal role in down-regulation of a cohort of genes in uterine leiomyoma

Cited by 12 publications

References 29 publications

Biological Convergence of Cancer Signatures

Biological Convergence of Cancer Signatures

Decreased expression of microRNA-29 family in leiomyoma contributes to increased major fibrillar collagen production

SDF1α/CXCR4 Signaling, via ERKs and the Transcription Factor Egr1, Induces Expression of a 67-kDa Form of Glutamic Acid Decarboxylase in Embryonic Hippocampal Neurons

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