MicroRNAs and their target gene networks in breast cancer

O’Day, Elizabeth; Lal, Ashish

doi:10.1186/bcr2484

Cited by 390 publications

(329 citation statements)

References 79 publications

(84 reference statements)

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“…From their downregulation, we can infer that these miRNAs have a metastasis suppressor function; loss of their expression leads to increased expression of their downstream oncogenic products. The role of let-7f in tumorigenesis and metastasis is well known (O'Day and Lal, 2010); therefore, we did not place much emphasis on this miRNA. However, miR-22 is a relatively new player and has been linked to cellular metabolism and chronic inflammatory diseases such as osteoarthritis (Iliopoulos et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this possibility, we observed elevated miR-200a in metastatic cancer cells compared with parental cells or TMD-231 cells. miR-17-5P has been suggested as a tumor suppressor in breast cancer; its expression was lower in lung metastatic cancer cells compared with other cell types (O'Day and Lal, 2010). The protumorigenic and prometastatic miRNA miR-19b was upregulated in metastatic cells (Table 2), whereas the antimetastatic miR-16 was downregulated in lung metastatic cells (Table 3) (Hurst et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

et al. 2010

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Metastasis in breast cancer carries a disproportionately worse prognosis than localized primary disease. To identify microRNAs (miRNA) involved in metastasis, the expression of 254 miRNAs was measured across the following cell lines using microarray analysis: MDA-MB-231 breast cancer cells, cells that grew as a tumor in the mammary fat pad of nude mice (TMD-231), metastatic disease to the lungs (LMD-231), bone (BMD-231) and adrenal gland (ADMD-231). A brain-seeking variant of this cell line (231-BR) was used additionally in validation studies. Twenty miRNAs were upregulated and seven were downregulated in metastatic cancer cells compared with TMD-231 cells. The expression of the tumor suppressor miRNAs let-7 and miR-22 was consistently downregulated in metastatic cancer cells. These metastatic cells expressed higher levels of putative/proven miR-22 target oncogenes ERBB3, CDC25C and EVI-1. Introduction of miR-22 into cancer cells reduced the levels of ERBB3 and EVI-1 as well as phospho-AKT, an EVI-1 downstream target. The miR-22 primary transcript is located in the 5 0 -untranslated region of an open reading frame C17orf91, and the promoter/enhancer of C17orf91 drives miR-22 expression. We observed elevated C17orf91 expression in non-basal subtype compared with basal subtype breast cancers. In contrast, elevated expression of EVI-1 was observed in basal subtype and was associated with poor outcome in estrogen receptor-negative breast cancer patients. These results suggest that metastatic cancer cells increase specific oncogenic signaling proteins through downregulation of miRNAs. Identifying such metastasisspecific oncogenic pathways may help to manipulate tumor behavior and aid in the design of more effective targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

et al. 2010

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“…More recent research has established that it may also be driven by epigenetic alterations, including DNA methylation, histone modifications, and control of gene expression by noncoding RNAs such as microRNAs (miRNA; refs. 2,3). Understanding the molecular mechanisms involved in breast cancer initiation and progression will provide strategies to identify new diagnostic and prognostic markers while enabling better prevention and treatment.…”

Section: Introductionmentioning

confidence: 99%

Expression of miR-18a and miR-210 in Normal Breast Tissue as Candidate Biomarkers of Breast Cancer Risk

Shidfar

Scholtens

Bischof

et al. 2017

Cancer Prevention Research

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miRNAs are noncoding RNAs with abnormal expression in breast cancer; their expression in high-risk benign breast tissue may relate to breast cancer risk. We examined miRNA profiles in contralateral unaffected breasts (CUB) of patients with breast cancer and validated resulting candidates in two additional sample sets. Expression profiles of 754 mature miRNAs were examined using TaqMan Low Density Arrays in 30 breast cancer samples [15 estrogen receptor (ER)-positive and 15 ERnegative] and paired CUBs and 15 reduction mammoplasty controls. Pairwise comparisons identified miRNAs with significantly differential expression. Seven candidate miRNAs were examined using qRT-PCR in a second CUB sample set (40 cases, 20 ERþ, 20 ERÀ) and 20 reduction mammoplasty controls. Further validation was performed in 80 benign breast biopsy (BBB) samples; 40 from cases who subsequently developed breast cancer and 40 from controls who did not. Logistic regression, using tertiles of miRNA expression, was used to discriminate cases from controls. Seven miRNAs were differentially expressed in tumors and CUBs versus reduction mammoplasty samples. Among them, miR-18a and miR-210 were validated in the second CUB set, showing significantly higher expression in tumor and CUBs than in reduction mammoplasty controls. The expression of miR-18a and miR-210 was also significantly higher in BBB cases than in BBB controls. When both miR-18a and miR-210 were expressed in the upper tertiles in BBB, OR for subsequent cancer was 3.20, P ¼ 0.023. miR-18a and miR-210 are expressed at higher levels in CUBs of patients with breast cancer, and in BBB prior to cancer development, and are therefore candidate breast cancer risk biomarkers.

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confidence: 99%

“…miR regulation results in inhibition of target gene expression through mRNA degradation and/or translational inhibition (21)(22)(23). Aberrant expression of miRs is closely associated with various human diseases, including breast cancer (23)(24)(25). Among miRs dysregulated in breast cancers, the miR-200 family is often found down-regulated (26,27) and subject to aberrant epigenetic silencing (28 -30).…”

mentioning

confidence: 99%

miR-200a Regulates Nrf2 Activation by Targeting Keap1 mRNA in Breast Cancer Cells

Eades¹,

Yang²,

Yao

et al. 2011

Journal of Biological Chemistry

282

180

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NF-E2-related factor 2 (Nrf2) is an important transcription factor that activates the expression of cellular detoxifying enzymes. Nrf2 expression is largely regulated through the association of Nrf2 with Kelch-like ECH-associated protein 1 (Keap1), which results in cytoplasmic Nrf2 degradation. Conversely, little is known concerning the regulation of Keap1 expression. Until now, a regulatory role for microRNAs (miRs) in controlling Keap1 gene expression had not been characterized. By using miR array-based screening, we observed miR200a silencing in breast cancer cells and demonstrated that upon re-expression, miR-200a targets the Keap1 3-untranslated region (3-UTR), leading to Keap1 mRNA degradation. Loss of this regulatory mechanism may contribute to the dysregulation of Nrf2 activity in breast cancer. Previously, we have identified epigenetic repression of miR-200a in breast cancer cells. Here, we find that treatment with epigenetic therapy, the histone deacetylase inhibitor suberoylanilide hydroxamic acid, restored miR-200a expression and reduced Keap1 levels. This reduction in Keap1 levels corresponded with Nrf2 nuclear translocation and activation of Nrf2-dependent NAD(P)H-quinone oxidoreductase 1 (NQO1) gene transcription. Moreover, we found that Nrf2 activation inhibited the anchorage-independent growth of breast cancer cells. Finally, our in vitro observations were confirmed in a model of carcinogen-induced mammary hyperplasia in vivo. In conclusion, our study demonstrates that miR-200a regulates the Keap1/Nrf2 pathway in mammary epithelium, and we find that epigenetic therapy can restore miR200a regulation of Keap1 expression, therefore reactivating the Nrf2-dependent antioxidant pathway in breast cancer.

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MicroRNAs and their target gene networks in breast cancer

Cited by 390 publications

References 79 publications

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

Expression of miR-18a and miR-210 in Normal Breast Tissue as Candidate Biomarkers of Breast Cancer Risk

miR-200a Regulates Nrf2 Activation by Targeting Keap1 mRNA in Breast Cancer Cells

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