ArticleCell death & disease2019
miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 127 citations in OpenAlex.
- The miRNA-4330/ABCG2 axis overcomes drug resistance and cancer progression in both ER-positive and ER-negative resistant breast cancer cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- NR4A3high mast cells promote ovarian cancer metastasis by reprogramming tumor-associated macrophages via JAK2/STAT6 signaling.Translational oncology · 2025Article
- Inferring single-cell and spatial microRNA activity from transcriptomics data.Communications biology · 2025Article
- Dual-regulatory miRNAs: master regulators and therapeutic targets in bone-metastatic breast cancer.Frontiers in molecular biosciences · 2025Review
- Identifying the Interaction Between Tuberculosis and SARS-CoV-2 Infections via Bioinformatics Analysis and Machine Learning.Biochemical genetics · 2024Article
- DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma.Translational oncology · 2024Article
- LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.Molecular therapy. Nucleic acids · 2024Article
- LINC00665 promotes glycolysis in lung adenocarcinoma cells via the let-7c-5p/HMMR axis.Journal of bioenergetics and biomembranes · 2024Article
- The modulation of immune cell death in connection to microRNAs and natural products.Frontiers in immunology · 2024Review
- NR4A3 inhibits the tumor progression of hepatocellular carcinoma by inducing cell cycle G0/G1 phase arrest and upregulation of CDKN2AIP expression.International journal of biological sciences · 2024Article
- A novel circular RNA, circMAML3, promotes tumor progression of prostate cancer by regulating miR-665/MAPK8IP2 axis.Cell death discovery · 2023Article
- Hsa_circ_0009092/miR-665/NLK signaling axis suppresses colorectal cancer progression via recruiting TAMs in the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2023Article
- Review
- miR-144-3p represses hepatocellular carcinoma progression by affecting cell aerobic glycolysis via FOXK1.International journal of experimental pathology · 2023Article
- Hsa_circ_0129047 sponges miR-665 to attenuate lung adenocarcinoma progression by upregulating protein tyrosine phosphatase receptor type B.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- circAR-E2E4-miR-665-STAT3 axis is a potential regulatory network in triple-negative breast cancer.Heliyon · 2023Article
- Article
- Microarray data analysis to identify miRNA biomarkers and construct the lncRNA-miRNA-mRNA network in lung adenocarcinoma.Medicine · 2022Article
- CircRNA-3302 promotes endothelial-to-mesenchymal transition via sponging miR-135b-5p to enhance KIT expression in Kawasaki disease.Cell death discovery · 2022Article
- Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration.Biomolecules · 2022Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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