Distinct expressions of microRNAs that directly target estrogen receptor α in human breast cancer

Yoshimoto, Nobuyasu; Toyama, Tatsuya; Takahashi, Satoru; Sugiura, Hiroshi; Endo, Yumi; Iwasa, Mitsuhiro; Fujii, Yoshitaka; Yamashita, Hiroko

doi:10.1007/s10549-011-1672-2

Cited by 75 publications

(65 citation statements)

References 36 publications

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“…The differential expression observed in our study demonstrates that TN breast carcinomas are characterized by the expression of miRNAs that downregulate ESR1 expression, such as let-7b (Zhao et al 2011a,b, Quesne et al 2012) and miR-18a/b (Leivonen et al 2009, Liu et al 2009, Yoshimoto et al 2011. According to this observation, we found that miR-934 was the most significantly modulated miRNA in TN breast cancer, and confirmed this by our analyses of data from the TCGA database (2012).…”

Section: Discussionsupporting

confidence: 85%

VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

Castilla¹,

López-García²,

Atienza³

et al. 2014

Endocrine-Related Cancer

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Vestigial-like 1 (VGLL1) is a poorly characterized gene encoding a transcriptional co-activator structurally homologous to TAZ and YAP that modulates the Hippo pathway in Drosophila. In this study, we examined the expression of VGLL1 and its intronic miRNA, miR-934, in breast cancer. VGLL1 and miR-934 expression miRNA profiling was carried out on frozen samples of grade 3 invasive ductal carcinomas. VGLL1 protein was also examined in 433 sporadic and BRCA1-associated breast carcinomas on tissue microarrays. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to confirm differences in VGLL1 and miR-934 expression in different breast cancer subtypes, and to correlate their expression with that of other genes and miRNAs. Of 28 miRNAs differentially expressed in estrogen receptor (ER)-positive and ER-negative grade 3 breast carcinomas, miR-934 was most strongly upregulated in ER-negative carcinomas, and its expression was correlated with that of VGLL1. Nuclear VGLL1 expression was observed in 13% of sporadic breast carcinomas, and while VGLL1 was only occasionally found in luminal A (0.70%) and B (5.60%) carcinomas, it was often expressed in HER2-positive (17%), triple-negative (TN) breast carcinomas (O40%) and BRCA1-associated TN carcinomas (O50%). These findings were confirmed in the TCGA dataset, which revealed positive associations with luminal progenitor genes (GABRP, SLC6A14, FOXC1, PROM1, and BBOX1) and strong negative correlations with ER-associated genes (ESR1, C6ORF211, GATA3, and FOXA1). Moreover, VGLL1 expression was associated with reduced overall survival. In conclusion, VGLL1 and miR-934 are mainly expressed in sporadic and BRCA1-associated TN basal-like breast carcinomas, and their coordinated expression, at least partially mediated by the direct modulation of ESR1, might be involved in the maintenance of a luminal progenitor phenotype.

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Section: Discussionsupporting

confidence: 85%

VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

Castilla¹,

López-García²,

Atienza³

et al. 2014

Endocrine-Related Cancer

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“…It has been reported that miR-18b has a role as a tumor suppressor gene by targeting the MDM2-p53 pathway in melanoma (11). Moreover, miR-18b is abnormally expressed in gastric cancer (12), breast cancer (13) and nasopharynx cancer (14). The present study indicated that miR-18b exhibited pathologically low expression levels in PE placentas; however, the pathological mechanism of miR-18b in the pathogenesis of PE remains poorly studied (15).…”

Section: Introductionmentioning

confidence: 49%

Expression and role of microRNA 18b and hypoxia inducible factor‑1α in placental tissues of preeclampsia patients

Wang

Weng

et al. 2017

Exp Ther Med

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Abstract. Abnormal expression of hypoxia inducible factor-1α (HIF-1α) is closely associated with various diseases. By detecting the mRNA and protein expression levels of microRNA 18b (miR-18b) and HIF-1α in placental tissues of preeclampsia (PE) patients and studying the effects of miR-18b on total cellular metabolic activity, migration and invasion in normal human trophoblast cell lines (HTR-8/SVneo), the present study aimed to investigate the effect of miR-18b on targeted regulation of HIF-1α and its clinical significance in the development of PE. Expression levels of miR-18b and HIF-1α mRNA in PE placental tissues were detected by reverse transcription-quantitative polymerase chain reaction and corresponding expression levels of HIF-1α protein were analyzed by western blotting. miR-18b overexpression and inhibited miR-18b expression in HTR-8/SVneo cells, which were constructed by transfecting miR-18b mimic and inhibitor, respectively, were investigated and the total cellular metabolic activity, migration and invasion abilities in different groups of cells were compared. Expression levels of miR-18b were significantly reduced in PE placental tissues and miR-18b inhibitor-transfected HTR-8/SVneo cells, whereas the expression levels of HIF-1α were significantly increased in PE placental tissues and significantly decreased in miR-18b mimic-transfected HTR-8/SVneo cells. Overexpression of miR-18b inhibited the expression of HIF-1α and reduced the cell invasion, migration and viability of HTR-8/SVneo cells. However, inhibition of miR-18b expression promoted the expression of HIF-1α and increased the cell invasion, migration and total cellular metabolic activity of HTR-8/SVneo cells. The present study indicated that abnormal expression of HIF-1α exhibited in PE placental tissues was regulated by miR-18b. Furthermore miR-18b expression was demonstrated to affect cell invasion, migration and viability through target regulation of HIF-1α. The results of the present study suggest that miR-18b and HIF-1α may have important roles in the development of PE.

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“…We recently analyzed expressions of microRNAs (miRNAs) that directly target ER in breast cancer. We found that miR-206 and miR-18a were downregulated in ER-positive breast cancer compared with ER-negative tumors and that low miR-18b expression was significantly associated with improved survival in HER2-negative breast cancer, although miR-18b expression was not correlated with ER protein expression (Kondo et al 2008, Yoshimoto et al 2011.…”

Section: Introductionmentioning

confidence: 87%

“…Among differentially expressed 67 miRNAs, the above 12 miRNAs, especially let-7a, miR-10a, miR-10b, miR-15a, miR-26a, miR-29c, miR-34a, miR-146a, and miR-342-3p, have been reported to be related to breast cancer development and carcinogenesis (Mattie et al 2006, Blenkiron et al 2007, O'Day & Lal 2010. miR-193b has been reported to be related to ERa (Yoshimoto et al 2011). Moreover, we referred to the reported mRNA microarray analyses to classify luminal A and luminal B subtypes in order to select key genes (Sorlie et al 2003, Parker et al 2009), including FOXA1, NAT1, MAPT, XBP1, and BCL2, which have target sequences in the 3 0 -UTR regions of 67 differentially expressed miRNAs according to in silico analysis using TargetScan, PicTar, and MiRanda, and selected miR-146a and miR-1290, which were downregulated in ER high Ki67 low tumors.…”

Section: Western Blottingmentioning

confidence: 99%

miR-1290 and its potential targets are associated with characteristics of estrogen receptor α-positive breast cancer

Endo

Toyama

Takahashi

et al. 2012

Endocrine-Related Cancer

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Recent analyses have identified heterogeneity in estrogen receptor a (ERa)-positive breast cancer. Subtypes called luminal A and luminal B have been identified, and the tumor characteristics, such as response to endocrine therapy and prognosis, are different in these subtypes. However, little is known about how the biological characteristics of ER-positive breast cancer are determined. In this study, expression profiles of microRNAs (miRNAs) (let-7a, miR-15a, miR-26a, miR-34a, miR-193b, and miR-342-3p). We picked up 11 genes that were potential target genes of the selected miRNAs and that were differentially expressed in ER high Ki67 low tumors and ER low Ki67 high tumors. Protein expression patterns of the selected target genes were analyzed in 256 ER-positive breast cancer samples by immunohistochemistry: miR-1290 and its putative targets, BCL2, FOXA1, MAPT, and NAT1, were identified. Transfection experiments revealed that introduction of miR-1290 into ER-positive breast cancer cells decreased expression of NAT1 and FOXA1. Our results suggest that miR-1290 and its potential targets might be associated with characteristics of ER-positive breast cancer.

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Distinct expressions of microRNAs that directly target estrogen receptor α in human breast cancer

Cited by 75 publications

References 36 publications

VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

Expression and role of microRNA 18b and hypoxia inducible factor‑1α in placental tissues of preeclampsia patients

miR-1290 and its potential targets are associated with characteristics of estrogen receptor α-positive breast cancer

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