Crucial Role for Early Growth Response-1 in the Transcriptional Regulation of miR-20b in Breast Cancer

Li, Dongping; Ilnytskyy, Yaroslav; Kovalchuk, Anna; Khachigian, Levon M.; Bronson, Roderick T.; Wang, Bo; Kovalchuk, Olga

doi:10.18632/oncotarget.1165

Cited by 62 publications

(61 citation statements)

References 58 publications

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“…Egr1 is expressed at high levels in transformed differentiated cells and functions as a proto-oncogene in certain tumor types. [33][34][35] Consistently, we find high levels of Cdk6 mRNA paralleled by a statistically significant upregulation of Egr1 in transformed BCR-ABL p1851 cells (supplemental Figure 6A). Chromatin immunoprecipitation (ChIP) analysis revealed the presence of CDK6 at the Egr1 promoter at levels comparable to its binding to the p16…”

Section: Cdk6 Directly Regulates Egr1 Expression In Hematopoietic Cellssupporting

confidence: 73%

CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

Scheicher

Hoelbl-Kovacic

Bellutti

et al. 2015

Blood

191

185

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Section: Cdk6 Directly Regulates Egr1 Expression In Hematopoietic Cellssupporting

confidence: 73%

CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

Scheicher

Hoelbl-Kovacic

Bellutti

et al. 2015

Blood

191

185

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“…The higher levels of EGR1 transcription factor in HFDO when compared to CDO tumors, while counter to its previously reported tumor suppressor function (Huang et al , 1997), is consistent with its recently reported role as an oncogene (Li et al , 2013) and in enhancing drug-resistance of breast cancer cells (Tao et al , 2013). Moreover, the lack of Dox treatment effects on the frequencies of basal (CD29 hi CD24 + ), luminal (CD29 lo CD24 + ) and tumor-initiating (CD29 hi CD24 + Thy1+) epithelial subpopulations in HFDO, and the higher transcript levels of stem cell markers Notch 1 and Aldh1 in HFDO than in CDO tumors are congruent with the reported positive association between drug insensitivity and expansion of breast cancer stem cells.…”

Section: Discussionsupporting

confidence: 86%

Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice

Montales

Melnyk

Liu

et al. 2016

Endocrine-Related Cancer

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The emerging links between breast cancer and metabolic dysfunctions spawned by the obesity pandemic predict a disproportionate early disease onset in successive generations. Moreover, sensitivity to chemotherapeutic agents may be influenced by the patient’s metabolic status to affect disease outcome. Maternal metabolic stress as a determinant of drug response in progeny is not well-defined. Here, we evaluated mammary tumor response to doxorubicin in female mouse mammary tumor virus-Wnt1-transgenic offspring exposed to a metabolically-compromised environment imposed by maternal high-fat diet; control progeny were from dams consuming diets with regular fat content. Maternal high-fat diet exposure increased tumor incidence and reduced tumor latency but did not affect tumor volume response to doxorubicin, when compared to control diet exposure. However, doxorubicin-treated tumors from high-fat diet-exposed offspring demonstrated higher proliferation status (Ki-67), mammary stem cell-associated gene expression (Notch1, Aldh1), and basal stem cell-like (CD29hiCD24+) epithelial subpopulation frequencies, than tumors from control diet progeny. Notably, all epithelial subpopulations [CD29hiCD24+, CD29loCD24+, CD29hiCD24+Thy1+] in tumors from high-fat diet-exposed offspring were refractory to doxorubicin. Further, sera from high-fat diet-exposed offspring promoted sphere formation of mouse mammary tumor epithelial cells and of human MCF7 cells. Untargeted metabolomics analyses identified higher levels of kynurenine and 2-hydroxyglutarate in plasma of high-fat diet than control diet offspring. Kynurenine/doxorubicin co-treatment of MCF7 cells enhanced mammosphere-formation ability and decreased apoptosis, relative to doxorubicin only-treated cells. Maternal metabolic dysfunctions during pregnancy and lactation may be targeted to reduce breast cancer risk and improve early drug response in progeny and may inform clinical management of disease.

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“…Furthermore, functional analysis indicated that ZNF267 increased the proliferation rate and migration of HCC cells in vitro (Schnabl et al, 2011). In this study, ZNF238 was targeted by over-expressed miR-20b, which was reported to be an oncogenic miRNA (Li et al, 2013). Conversely, ZNF267 was a target gene of the antineoplastic miRNAs -23a and -23b (Goto et al, 2014;Xishan et al, 2014), both of which were downregulated in our study.…”

Section: Discussionsupporting

confidence: 55%

Regulation of the expression of zinc finger protein genes by microRNAs enriched within acute lymphoblastic leukemia-derived microvesicles

Lü¹,

Chen²,

Tao³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Microvesicles (MVs) are submicrometric membrane fragments that can "engulf" cytoplasmic contents such as microRNAs (miRNAs) from their cellular origin. The study of miRNAs carried within MVs might provide insights into the roles that miRNAs play in the underlying pathophysiologic processes of acute lymphoblastic leukemia (ALL). We identified numerous dysregulated MV miRNAs in patients with B-and T-cell ALL by using Agilent microarray analysis. Selected miRNAs obtained by microarray profiling were validated using quantitative reverse transcription-polymerase chain reaction. Using bioinformatic tools, we found that 118 and 116 miRNAs from Band T-ALL MVs, respectively, regulated the expression of zinc finger protein (ZFP) genes. For example, zinc finger protein 238 (ZNF238), known as a tumor suppressor, was regulated by miR-20b over-expression. Conversely, ZNF267, a cancer-promoting factor, was mediated by downregulated miR-23a and miR-23b. Considering that miRNAs are generally believed to repress gene expression, antineoplastic ZNF238 was likely inhibited while the level of oncogenic ZNF267 was likely increased by miRNA dysregulation, leading to modification of the ALL microenvironment. In addition, gene ontology and signaling pathway analysis demonstrated that a subset of the ZFP genes targeted by altered MV miRNAs are involved in cellular biological processes including proliferation, differentiation, apoptosis, and cell cycle regulation. These findings indicated that cancer-associated MV miRNAs and their target ZFP genes might be novel pathogenic factors in ALL. However, the specific roles exerted by MV miRNAs and their target ZFP genes on the pathological mechanisms of ALL remain to be further understood.

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Crucial Role for Early Growth Response-1 in the Transcriptional Regulation of miR-20b in Breast Cancer

Cited by 62 publications

References 58 publications

CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice

Regulation of the expression of zinc finger protein genes by microRNAs enriched within acute lymphoblastic leukemia-derived microvesicles

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