Detail
Experiment ID:
EXP00493
Reference:
- Title: miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer.
- Author: Zhao XG, Hu JY, Tang J, Yi W, Zhang MY, Deng R, Mai SJ, Weng NQ, Wang RQ, Liu J, Zhang HZ, He JH, Wang HY
- Journal: Cell death & disease.2019 06 17;10(7):479.doi:10.1038/s41419-019-1705-z.
- Abstract: Cancer metastasis is the main cause of death in breast cancer (BC) patients. Therefore, prediction and treatment of metastasis is critical for enhancing the survival of BC patients. In this study, we aimed to identify biomarkers that can predict metastasis of BC and elucidate the underlying mechanism of the functional involvement of such markers in metastasis. miRNA expression profile was analyzed using a custom microarray system in 422 BC tissues. The relationship between the upregulated miR-665, metastasis and survival of BC was analyzed and verified in another set of 161 BC samples. The biological function of miR-665 in BC carcinogenesis was explored with in vitro and in vivo methods. The target gene of miR-665 and its signaling cascade were also analyzed. There are 399 differentially expressed miRNAs between BC and noncancerous tissues, of which miR-665 is the most upregulated miRNA in the BC tissues compared with non-tumor breast tissues (P < 0.001). The expression of miR-665 predicts metastasis and poor survival in 422 BC patients, which is verified in another 161 BC patients and 2323 BC cases from online databases. Ectopic miR-665 expression promotes epithelial-mesenchymal transition (EMT), proliferation, migration and invasion of BC cells, and increases tumor growth and metastasis of BC in mice. Bioinformatics, luciferase assay and other methods showed that nuclear receptor subfamily 4 group A member 3 (NR4A3) is a target of miR-665 in BC. Mechanistically, we demonstrated that miR-665 promotes EMT, invasion and metastasis of BC via inhibiting NR4A3 to activate MAPK/ERK kinase (MEK) signaling pathway. Our study demonstrates that miR-665 upregulation is associated with metastasis and poor survival in BC patients, and mechanistically, miR-665 enhances progression of BC via NR4A3/MEK signaling pathway. This study provides a new potential prognostic biomarker and therapeutic target for BC patients.
- PMID: 31209222
Expression Profile:
- Description:The prognostic and predictive value of a five-microRNA-based classifier in breast cancer
- Organism:Homo sapiens
- Source:GEO
- Source ID:GSE57897
- Platform: GPL18722
- Number of samples:453
- Overall design:422 breast cancer specimens and 31 noncancerous breast tissues
- Instrument:Homo sapiens microRNA array
Design and Sample:
- Cancer Type:breast cancer
- Cancer SubType:N/A
- Cell Line:N/A
- Experimental Design:cancer vs normal
- Case Sample:breast cancer
- Control Sample:normal tissue
- Num of Case:422
- Num of Control:31
- Quantification Software:Limma
- Num of miRNAs:1841
Identification:
- Num of Up:414
- Num of Down:481
Time Info:
- Create Time2021-06-04
- Update Time:2021-06-07
Status:
| miRNA ID | Cancer Type | Design | logFC | AveExpr | T value | P value | adj Pvalue | Status | Plot |
|---|