MicroRNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1

Yang, Shangbin; Li, Y; Gao, Jiajia; Zhang, T; Li, S; Luo, Aiping; Chen, H; Ding, Fang; Wang, X; Liu, Z

doi:10.1038/onc.2012.432

Cited by 213 publications

(187 citation statements)

References 58 publications

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“…Therefore, it is possible that upregulated PPARG and downregulated JUND may exert opposite effects on osteosarcoma metastasis via competitively regulating the expression of SAT1. In addition, upregulation of the FOSL1 oncogene is involved in breast cancer migration and invasion (46). FOXA2 may function as a suppressor of lung cancer metastasis by inhibiting TGF-β-induced epithelial to mesenchymal transition (47).…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs

Jia

Bai

et al. 2017

Molecular Medicine Reports

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Abstract. The present study aimed to understand the molecular mechanisms underlying osteosarcoma metastasis. Microarray dataset GSE49003 was downloaded from the Gene Expression Omnibus database and used for analysis. Raw expression data were preprocessed using the preprocessCore, impute and aggregate packages in R. Differentially expressed genes (DEGs) between metastatic and non-metastatic osteosarcoma cell lines were screened using the limma package following exclusion of DEGs with a higher significance in intra-groups compared with inter-groups using the genefilter package. Enrichment analysis was performed on DEGs using TargetMine, followed by identification of transcription factors (TFs) and microRNAs (miRNAs). Regulatory networks were constructed using Cytoscape software. A total of 248 upregulated and 208 downregulated genes were obtained. The upregulated genes were significantly enriched in the following pathways: Downregulation of transforming growth factor β (TGF-β) receptor signaling and TGF-β receptor signaling activates SMADs; these upregulated genes included protein phosphatase 1, regulatory subunit 15A, transforming growth factor, β receptor II and ubiquitin carboxyl-terminal hydrolase L5. In addition, some upregulated genes were enriched in lung cancer disease ontology, including epidermal growth factor receptor (EGFR), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), runt-related transcription factor 3 (RUNX3) and secreted frizzled-related protein 1 (SFRP1). Conversely, the downregulated genes were significantly enriched in extracellular matrix-associated pathways or functions, such as collagen, type XII, α 1; collagen, type I, α 1; collagen, type IV, α 1; and collagen, type V, α 1. In addition, some downregulated genes were significantly enriched in the TGF-β signaling pathway, including bone morphogenetic protein 4, inhibitor of DNA binding 3 and SMAD family member 6. A total of 10 TFs and 84 miRNAs (e.g. miR-21-5p) were deemed to be associated with DEGs. In conclusion, DEGs enriched in the downregulation of TGF-β receptor signaling, TGF-β receptor signaling activates SMADs and TGF-β signaling pathways, as well as the extracellular matrix may be implicated in the progression of osteosarcoma metastasis. Dysregulated EGFR, IGF2BP3, RUNX3 and SFRP1 may contribute to the metastasis of osteosarcoma to the lungs. In addition, screened TFs and miR-21-5p may be associated with metastasis via target genes.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs

Jia

Bai

et al. 2017

Molecular Medicine Reports

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“…In breast cancer, miR34c is related to self-renewal and epithelialmesenchymal transition, and miR34a/c regulates breast cancer migration and invasion (12,26). Interestingly, miR34a directly targets CD44 and suppresses tumor development and metastasis in prostate cancer stem cells (20).…”

Section: Discussionmentioning

confidence: 99%

Targeting of miR34a–NOTCH1 Axis Reduced Breast Cancer Stemness and Chemoresistance

et al. 2014

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Human breast cancers include cancer stem cell populations as well as nontumorigenic cancer cells. Breast cancer stem cells have self-renewal capability and are resistant to conventional chemotherapy. miRNAs regulate the expression of many target genes; therefore, dysregulation of miRNAs has been associated with the pathogenesis of human diseases, including cancer. However, a role for miRNA dysregulation in stemness and drug resistance has yet to be identified. Members of the miR34 family are reportedly tumor-suppressor miRNAs and are associated with various human cancers. Our results confirm that miR34a expression was downregulated in MCF7/ADR cells compared with MCF7 cells. We hypothesized that this reduction was due to the p53 (TP53) mutation in MCF7/ ADR cells. In this study, we found that primary and mature miR34a were suppressed by treatment with p53 RNAi or the dominant-negative p53 mutant in MCF7 cells. Ectopic miR34a expression reduced cancer stem cell properties and increased sensitivity to doxorubicin treatment by directly targeting NOTCH1. Furthermore, tumors from nude mice treated with miR34a were significantly smaller compared with those of mice treated with control lentivirus. Our research suggests that the ectopic expression of miR34a represents a novel therapeutic approach in chemoresistant breast cancer treatment. Cancer Res; 74(24); 7573-82. Ó2014 AACR.

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“…Recent work described that miR-34 suppresses invasion and metastasis of breast cancer by directly targeting Fra-1 (Yang et al, 2012); other reports have shown that p53/miRNA-34 axis regulates snail-dependent epithelialmesenchymal transition in tumorigenesis (Kim et al, 2011). Ectopic miR-34 expression was shown to induce apoptosis, cell-cycle arrest, and senescence (Hermeking, 2010).…”

mentioning

confidence: 99%

“…In triple-negative breast cancer, which is characterized mainly by ERa, PgR, and HER2 absence, miR-34b, but not miR-34a or miR-34c was reported to be negative correlated with diseasefree survival and an overall survival (Svoboda et al, 2012). A microarray conducted in breast cancer has shown that miR34a was significantly downregulated in DCIS and IDC compared with benign tissue (Yang et al, 2012). However, the role of miR-34a in breast cancer still needs to be further elucidated.…”

mentioning

confidence: 99%

MicroRNA-34a Suppresses Cell Proliferation by Targeting LMTK3 in Human Breast Cancer MCF-7 Cell Line

Zhao

Guo

Li³

et al. 2013

DNA and Cell Biology

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Breast cancer remains the leading cause of cancer mortality in females, and about 70% of the primary breast cancer patients are diagnosed ERa-positive, which is the most common type of breast cancer. MicroRNA-34a (miR-34a) has been shown to be a master regulator of tumor suppression in many types of cancers including breast cancer. However, the role of miR-34a in ERa-positive breast cancer has not been elucidated. Here, we find that in MCF-7, which is an ERa-positive breast cancer cell line, miR-34a is remarkably downregulated after E2 treatment. Overexpression of miR-34a by lentivirus suppresses cell proliferation, S phase ratio, and tumor formation in an E2-dependent manner in vitro. According to the mRNA sequence, lemur tyrosine kinase 3 (LMTK3), which is an important regulator of estrogen receptor alpha (ERa), is a predicted target of miR-34a. This is confirmed by dual luciferase reporter assay and the decrease of LMTK3 mRNA and protein levels after overexpression of miR-34a. Moreover, miR-34a overexpression decreases AKT signaling pathway and increases ERa phosphorylation status. Taken together, these results suggest that miR-34a inhibits breast cancer proliferation by targeting LMTK3 and might be used as an anti-ERa agent in breast cancer therapy.

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MicroRNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1

Cited by 213 publications

References 58 publications

Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs

Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs

Targeting of miR34a–NOTCH1 Axis Reduced Breast Cancer Stemness and Chemoresistance

MicroRNA-34a Suppresses Cell Proliferation by Targeting LMTK3 in Human Breast Cancer MCF-7 Cell Line

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