Effects of Oestrogen on MicroRNA Expression in Hormone-Responsive Breast Cancer Cells

Ferraro, Lorenzo; Ravo, Maria; Nassa, Giovanni; Tarallo, Roberta; Filippo, Maria Rosaria De; Giurato, Giorgio; Cirillo, Francesca; Stellato, Claudia; Silvestro, Silvana; Cantarella, Concita; Rizzo, Francesca; Cimino, Daniela; Friard, Olivier; Biglia, Nicoletta; Bortoli, Michele De; Cicatiello, Luigi; Nola, Ernesto; Weisz, Alessandro

doi:10.1007/s12672-012-0102-1

Cited by 60 publications

(60 citation statements)

References 71 publications

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“…Several evidences indicate that ERa is among the transcription factors regulating miRNA biogenesis in hormone-responsive BC cells (Bhat-Nakshatri et al, 2009;Castellano et al, 2009;Maillot et al, 2009;Yamagata et al, 2009;Cicatiello et al, 2010;Ferraro et al, 2010Ferraro et al, , 2011. More recently, global mapping of ERb binding to ERa-positive, hormone-responsive BC cells chromatin in vivo showed ERb interaction with several miRNA genes, suggesting the possible involvement of this receptor in hormonal control of small noncoding RNA biogenesis in this cell type (Grober et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer

et al. 2012

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Estrogen effects on mammary epithelial and breast cancer (BC) cells are mediated by the nuclear receptors ERa and ERb, transcription factors that display functional antagonism with each other, with ERb acting as oncosuppressor and interfering with the effects of ERa on cell proliferation, tumor promotion and progression. Indeed, hormone-responsive, ERa þ BC cells often lack ERb, which when present associates with a less aggressive clinical phenotype of the disease. Recent evidences point to a significant role of microRNAs (miRNAs) in BC, where specific miRNA expression profiles associate with distinct clinical and biological phenotypes of the lesion. Considering the possibility that ERb might influence BC cell behavior via miRNAs, we compared miRNome expression in ERb þ vs ERbÀ hormone-responsive BC cells and found a widespread effect of this ER subtype on the expression pattern of these non-coding RNAs. More importantly, the expression pattern of 67 miRNAs, including 10 regulated by ERb in BC cells, clearly distinguishes ERb þ , node-negative, from ERbÀ, metastatic, mammary tumors. Molecular dissection of miRNA biogenesis revealed multiple mechanisms for direct regulation of this process by ERb þ in BC cell nuclei. In particular, ERb downregulates miR-30a by binding to two specific sites proximal to the gene and thereby inhibiting pri-miR synthesis. On the other hand, the receptor promotes miR-23b, -27b and 24-1 accumulation in the cell by binding in close proximity of the corresponding gene cluster and preventing in situ the inhibitory effects of ERa on pri-miR maturation by the p68/DDX5-Drosha microprocessor complex. These results indicate that cell autonomous regulation of miRNA expression is part of the mechanism of action of ERb in BC cells and could contribute to establishment or maintenance of a less aggressive tumor phenotype mediated by this nuclear receptor.

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Section: Introductionmentioning

confidence: 99%

Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer

et al. 2012

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“…Studies on the effect of E2 on the expression pattern of miRs in MCF7 and ZR75 cell lines revealed 172 miRs that were up or downregulated. Notable miRs are miR-206, miR-34a, miR-17-5p, and miR-125 a/b, which act as tumour suppressors, and miR-21, miR-10B, and miR-155, which act as oncogenes 17 . Another study using an ACI rat model for the effect of E2 on the miR signature showed 33 dysregulated miRs 18 .…”

Section: Mirs Controlling Involution and Breast Cancermentioning

confidence: 99%

MicroRNAs in the development and neoplasia of the mammary gland

Jena¹

2017

F1000Res

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Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2) signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes.Studies using an ACI rat model showed similar findings of miR dysregulation due to excess E2, and a natural phenol antioxidant ellagic acid showed therapeutic properties by reversing the miR dysregulation. This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages) and their involvement in breast cancer progression. Further studies in this area will help us understand the molecular details of mammary gland biology,as well as miRs that could be therapeutic targets of breast cancer.

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“…miRNAome-wide profiling arrays, such as microarrays and qPCR arrays, have helped to define a signature of estrogen-regulated miRs. The first examples of such arrays are limited in their applicability to ERa signalling in humans, being performed in zebrafish, rat breast tissue and mouse spleen (Kovalchuk et al 2007, Dai et al 2008, and to date only around 15 studies have examined estrogen regulation of miRs in human cells (Iorio et al 2005, Bhat-Nakshatri et al 2009, Castellano et al 2009, Klinge 2009, Maillot et al 2009, Wickramasinghe et al 2009, Cicatiello et al 2010, Cochrane et al 2010, Di Leva et al 2010, Hah et al 2011, Ferraro et al 2012, Masuda et al 2012, Zhao et al 2013. Despite the majority of these being performed in MCF7 breast cancer cells, inconsistencies are evident, presumably attributable to differences in ligand, treatment duration, array platform, statistical processing and threshold setting as well as lab-specific cell line differences.…”

Section: Estrogen Modulation Of Mir Biogenesismentioning

confidence: 99%

“…One estrogen-responsive ERE was found in the miR-21 promoter, with five and four EREs identified in the miR-23bw27bw24-1 and miR-23aw27aw24-2 promoters respectively, although different cluster members showed differing extents of regulation (Bhat-Nakshatri et al 2008). Ferraro et al (2012) used this approach to compare responses in estrogen-treated MCF7 and ZR-75.1 cells. They demonstrated that miR-135a-2, miR-181c, miR-26b and the clustered miR-23a, miR-27a and miR-24-2 were estrogen-regulated in both cell lines and located within 10 kb of an ERa-binding site, while estrogenregulated miR-25, miR-26a, miR-424, miR-618, miR-760 and miR-942 were located in the intragenic region of Mutual regulation by steroid hormone receptors and microRNAs (miRs).…”

Section: Estrogen Modulation Of Mir Biogenesismentioning

confidence: 99%

Interplay between steroid signalling and microRNAs: implications for hormone-dependent cancers

Fletcher¹,

Dart²,

Bevan³

2014

Endocrine Related Cancer

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Hormones are key drivers of cancer development. To date, interest has largely been focussed on the classical model of hormonal gene regulation, but there is increasing evidence for a role of hormone signalling pathways in post-translational regulation of gene expression. In particular, a complex and dynamic network of bi-directional interactions with microRNAs (miRs) at all stages of biogenesis and during target gene repression is emerging. miRs, which act mainly by negatively regulating gene expression through association with 3 0 -UTRs of mRNA species, are increasingly understood to be important in development, normal physiology and pathogenesis. Given recent demonstrations of altered miR profiles in a diverse range of cancers, their ability to function as oncogenes or tumour suppressors, and hormonal regulation of miRs, understanding mechanisms by which miRs are generated and regulated is vitally important. miRs are transcribed by RNA polymerase II and then processed in the nucleus by the Drosha-containing Microprocessor complex and in the cytoplasm by Dicer, before mature miRs are incorporated into the RNA-induced silencing complex. It is increasingly evident that multiple cellular signalling pathways converge upon the miR biogenesis cascade, adding further layers of regulatory complexity to modulate miR maturation. This review summarises recent advances in identification of novel components and regulators of the Microprocessor and Dicer complexes, with particular emphasis on the role of hormone signalling pathways in regulating their activity. Understanding hormone regulation of miR production and how this is perturbed in cancer are critical for the development of miR-based therapeutics and biomarkers.

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Effects of Oestrogen on MicroRNA Expression in Hormone-Responsive Breast Cancer Cells

Cited by 60 publications

References 71 publications

Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer

Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer

MicroRNAs in the development and neoplasia of the mammary gland

Interplay between steroid signalling and microRNAs: implications for hormone-dependent cancers

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