Loss of Estrogen-Regulated microRNA Expression Increases HER2 Signaling and Is Prognostic of Poor Outcome in Luminal Breast Cancer

Bailey, Scott; Westerling, Thomas; Brown, Myles

doi:10.1158/0008-5472.can-14-1041

Cited by 78 publications

(61 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to that, miRNA profiling between ER+ or ER-breast cancer cells revealed differences [51,56]. In fact, Bailey et al demonstrated that ER binding sites located near miRNA are lost in differentially decreased miRNA in ER-breast cancer cell line [56].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cells (HUVEC) exposed to a physiological concentration of estradiol (E2; 1 nmol/L) for 24 hours. miRNAgene interactions were computationally predicted using Ingenuity Pathway Analysis and changes in miRNA levels were validated by qRT-PCR. Role of ER in the E2-induced miRNA was additionally confirmed by using specific ER agonists and antagonists. Results: miRNA array revealed that expression of 114 miRNA were significantly modified after E2 exposition. Further biological pathway analysis revealed cell death and survival, lipid metabolism, reproductive system function, as the top functions regulated by E2. We validated changes in the most significantly increased (miR-30b-5p, miR-487a-5p, miR-4710, miR-501-3p) and decreased (miR-378h and miR-1244) miRNA and the role of ER in these E2-induced miRNA was determined. Results showed that both classical, ERα and ERβ, and membrane-bound ER, GPER, differentially regulated specific miRNA. In silico analysis of validated miRNA promoters identified specific ER binding sites. Conclusion: Our findings identify differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER, and provide new insights by which estrogen can modulate endothelial function.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…As such, while ER can induce the expression of various GFRs and ligands [ e.g. , insulin-like growth factor 1 (IGF1), its receptor (IGFR), and the HER ligand transforming growth factor-α (TGFα) 31,32 ] or activate these pathways through its non-genomic activity, it can also inhibit the expression of key receptors such as HER1 and HER2 33,34 . Thus, endocrine therapy, by blocking ER genomic activities, can relieve this repression, resulting in increased expression of HER1 and HER2 receptors and downstream signaling 34 , which in turn can further promote resistance to endocrine therapies.…”

Section: Underlying Mechanisms Of Altered Er Activity In Endocrine Rementioning

confidence: 99%

The changing role of ER in endocrine resistance

et al. 2015

View full text Add to dashboard Cite

SUMMARY Estrogen receptor (ER) is expressed in approximately 70% of newly diagnosed breast tumors. Although endocrine therapy targeting ER is highly effective, intrinsic or acquired resistance is common, significantly jeopardizing treatment outcomes and minimizing overall survival. Even in presence of endocrine resistance, a continued role of ER signaling is suggested by several lines of clinical and preclinical evidence. Indeed, inhibition or down-regulation of ER reduces tumor growth in preclinical models of acquired endocrine resistance, and many patients with recurrent ER+ breast tumors progressing on one type of ER-targeted treatment still benefit from sequential endocrine treatments that target ER by a different mechanism. New insights into the nature and biology of ER have revealed several mechanisms sustaining altered ER signaling in endocrine-resistant tumors, including deregulated growth factor receptor signaling that results in ligand-independent ER activation, unbalanced ER co-regulator activity, and genomic alterations involving the ER gene ESR1. Therefore, biopsies of recurrent lesions are needed to assess the changes in epi/genomics and signaling landscape of ER and associated pathways in order to tailor therapies to effectively overcome endocrine resistance. In addition, more completely abolishing the levels and activity of ER and its co-activators, in combination with selected signal transduction inhibitors or agents blocking the upstream or downstream targets of the ER pathway, may provide a better therapeutic strategy in combating endocrine resistance.

show abstract

“…When the oligonucleotide, approximately 30nt in length, containing the lesion has been removed, Proliferating Cell Nuclear Antigen (PCNA) is loaded onto the DNA by Replicating Factor C (RFC) protein, as is the case in normal DNA replication. DNA polymerases δ and ε then mediate DNA repair synthesis across the gap using the undamaged strand as a template (Bailey et al, 2015;Murphy et al, 2015). Finally, the remaining nick is sealed by DNA ligase I.…”

Section: ) -Transcriptionmentioning

confidence: 99%