Estrogen Receptor β1 Expression Is Regulated by miR-92 in Breast Cancer

Al-Nakhle, Hakeemah; Burns, Philip A.; Cummings, Michele; Hanby, Andrew M.; Hughes, Tom; Satheesha, Sampoorna; Shaaban, Abeer M.; Smith, Laura; Speirs, Valerie

doi:10.1158/0008-5472.can-09-4104

Cited by 106 publications

(73 citation statements)

References 32 publications

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“…Moreover, in CLL B cells, miR-92a decreases pVHL expression, leading to accumulation of HIF1a and subsequently VEGF (30). Estrogen receptor ␤1 was demonstrated to be the target of miR-92a in breast cancer (31). Our current finding indicated that miR-92a represses the expression of CDH1 in ESCC.…”

Section: Discussionsupporting

confidence: 52%

microRNA-92a Promotes Lymph Node Metastasis of Human Esophageal Squamous Cell Carcinoma via E-Cadherin

Chen¹,

Zhao²,

Wang³

et al. 2011

Journal of Biological Chemistry

140

108

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microRNAs (miRNAs) regulate gene expression at the posttranscriptional level and play important roles in tumor initiation and progression. Recently, we examined the global miRNA expression profile of esophageal squamous cell carcinoma (ESCC) and demonstrated that miR-92a was highly expressed in tumor tissues. In this study, we found that the upregulation of miR-92a was significantly correlated with the status of lymph node metastasis and TNM stage in 107 ESCC patients. Moreover, the up-regulation of miR-92a was associated with poor survival of ESCC patients and might be used as an independent prognostic factor. Next, we investigated the role and mechanism of miR-92a in ESCC cells, and found that miR-92a modulated the migration and invasion but not apoptosis and proliferation of ESCC cells in vitro. We further demonstrated that miR-92a directly targeted the CDH1 3-UTR and repressed the expression of CDH1, a tumor metastasis suppressor. In addition, restoring of miR-92a-resistant CDH1 expression in miR-92a-overexpression cells recovered the pro-metastasis activity of miR-92a. Taken together, we demonstrated that miR-92a promotes ESCC cell migration and invasion at least partially via suppression of CDH1 expression, and patients with up-regulated miR-92a are prone to lymph node metastasis and thus have poor prognosis.Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer deaths worldwide. The incidence of esophageal cancer varies greatly by geographic location, where it is most common in China, Southeast Africa, and Japan. Compared with the high incidence of Barrett's associated adenocarcinoma in Europe and the United States (1), the incidence of esophageal squamous cell carcinoma (ESCC) 3 is prevalent in China. Despite the advances in therapy, ESCC is still one of the most lethal malignancies in China, with an overall 5-year survival rate of 20 -30% after surgery (2, 3). Tumor metastasis is primarily responsible for ESCC mortality, yet the molecular mechanism of metastatic dissemination remains unclear (4). Recent evidences suggest that miRNAs play an important role in tumor metastasis (5-8). miRNA is the noncoding RNA of ϳ22 nucleotides that regulates gene expression via degradation of target mRNAs or inhibition of protein translation. Hundreds of miRNAs have been identified, and some of them exhibit highly specific expression patterns in various tissues and species. More than 50% of annotated human miRNA genes are located in fragile chromosomal regions that are susceptible to amplification, deletion or translocation during the process of tumor development and can function either as oncogene or tumor suppressor (9). miR-92a belongs to the miR-17-92a cluster and is located on chromosome 13q32-33, a region frequently amplified in B-cell lymphoma (10, 11), lung cancer (12), and colorectal cancer (13). The polycistronic miR-17-92a cluster produces six mature miRNAs (miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a-1). Up-regulation of these miRNAs were found in B-cell...

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Section: Discussionsupporting

confidence: 52%

microRNA-92a Promotes Lymph Node Metastasis of Human Esophageal Squamous Cell Carcinoma via E-Cadherin

Chen¹,

Zhao²,

Wang³

et al. 2011

Journal of Biological Chemistry

140

108

View full text Add to dashboard Cite

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“…The potential role of ERb in breast cancer has been the subject of much debate and recent work in FBC by us and others shows this depends on the cell location and the type of isoforms expressed [9,44]. However, ERb is subject to complex regulation involving 3 0 UTRs [45] and microRNAs [46], and we need to further understand its biology before speculating on any role it may play in MBC.…”

Section: Discussionmentioning

confidence: 99%

A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences

Shaaban

Ball

Brannan

et al. 2011

Breast Cancer Res Treat

Self Cite

116

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Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERα, ERβ1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phenotype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERβ1/2 clusters. A striking feature was the occurrence of ERα on distinct clusters between genders. In female breast cancer, ERα clustered with PR and its isoforms; in male breast cancer, ERα clustered with ERβ isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.

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“…miR-22 represses ER α expression by directly targeting its 3′ untranslated region (UTR), which induces mRNA degradation (Pandey and Picard 2009). ER β 1 is often down-regulated in breast cancers, and analysis of primary breast tumors demonstrates this may be due to a negative correlation between miR-92 and ER β 1 mRNA and protein (Al-Nakhle et al 2010). In vitro experiments confirm this finding by showing that overexpression of miR-92 decreases ER β 1 via direct targeting of the ER β 3′ UTR (Al-Nakhle et al 2010).…”

Section: Breast Cancer and Ermentioning

confidence: 99%

Estrogen receptors and human disease: an update

2012

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A myriad of physiological processes in mammals are influenced by estrogens and the estrogen receptors (ERs), ERα and ERβ. As we reviewed previously, given the widespread role for estrogen in normal human physiology, it is not surprising that estrogen is implicated in the development or progression of a number of diseases. In this review, we are giving a 5-year update of the literature regarding the influence of estrogens on a number of human cancers (breast, ovarian, colorectal, prostate, and endometrial), endometriosis, fibroids, and cardiovascular disease. A large number of sophisticated experimental studies have provided insights into human disease, but for this review, the literature citations were limited to articles published after our previous review (Deroo and Korach in J Clin Invest 116(3):561–570, 2006) and will focus in most cases on human data and clinical trials. We will describe the influence in which estrogen’s action, through one of or both of the ERs, mediates the aforementioned human disease states.

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Estrogen Receptor β1 Expression Is Regulated by miR-92 in Breast Cancer

Cited by 106 publications

References 32 publications

microRNA-92a Promotes Lymph Node Metastasis of Human Esophageal Squamous Cell Carcinoma via E-Cadherin

microRNA-92a Promotes Lymph Node Metastasis of Human Esophageal Squamous Cell Carcinoma via E-Cadherin

A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences

Estrogen receptors and human disease: an update

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