ArticleOncotarget2016
A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Prognostic significance of SHP2 (PTPN11) expression in solid tumors: A meta-analysis.PloS one · 2022Pooled it
- Article
- miR-489 induces immunogenic cell death in breast cancer by targeting LAPTM4B.Frontiers in oncology · 2026Article
- Interplay Between MicroRNAs and Breast Cancer Therapies: Personalized Therapeutic Potential for HER2-Low Breast Cancer.Cancers · 2025Review
- Molecular imprinting of miR-559 on a peptide-immobilized poly L-DOPA/silica core-shell and in vitro investigating its effects on HER2-positive breast cancer cells.Drug delivery and translational research · 2023Article
- Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer.Cancers · 2023Review
- MicroRNAs: A Link between Mammary Gland Development and Breast Cancer.International journal of molecular sciences · 2022Review
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- miR-489 Confines Uncontrolled Estrogen Signaling through a Negative Feedback Mechanism and Regulates Tamoxifen Resistance in Breast Cancer.International journal of molecular sciences · 2022Article
- Blood Circulating Non-Coding RNAs for the Clinical Management of Triple-Negative Breast Cancer.Cancers · 2022Review
- miR-514a-3p: a novel SHP-2 regulatory miRNA that modulates human cytotrophoblast proliferation.Journal of molecular endocrinology · 2022Article
- Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy.Frontiers in oncology · 2022Review
- Evaluation of Serum MicroRNAs (miR-9-5p, miR-17-5p, and miR-148a-3p) as Potential Biomarkers of Breast Cancer.BioMed research international · 2022Article
- Fasudil prevents neomycin-induced hair cell damage by inhibiting autophagy through the miR-489/NDP52 signaling pathway in HEI-OC1 cells.Experimental and therapeutic medicine · 2022Article
- Article
- The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer.Nutrients · 2021Review
- miR-489-3p/SIX1 Axis Regulates Melanoma Proliferation and Glycolytic Potential.Molecular therapy oncolytics · 2020Article
- Expression of miR-221 and miR-489 in breast cancer patients and their relationship with prognosis.Oncology letters · 2020Article
- miR‑489 promotes apoptosis and inhibits invasiveness of glioma cells by targeting PAK5/RAF1 signaling pathways.Oncology reports · 2019Article
- MicroRNA-9 exerts antitumor effects on hepatocellular carcinoma progression by targeting HMGA2.FEBS open bio · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several microRNAs (miRNAs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRNAs dysregualted in HER2-positive breast cancer cells. Our molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially through the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenecity and tumor growth in xenograft mice. Mechanistically, we found that overexpression of miR-489 led to the decreased levels of HER2 and SHP2 and thus attenuated HER2-downstream signaling. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2-SHP2-MAPK and miR-489 signaling pathways form a mutually inhibitory loop. Using quantitative real-time PCR analysis and Fluorescent in situ hybridization technique (FISH), we found that miR-489 was expressed at significantly lower level in tumor tissues compared to the adjacent normal tissues. Downregulation of miR-489 in breast cancers was associated with aggressive tumor phenotypes. Overall, our results define a double-negative feedback loop involving miR-489 and the HER2-SHP2-MAPK signaling axis that can regulate breast cancer cell proliferation and tumor progression and might have therapeutic relevance for HER2-positive breast cancer.
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Registered trials
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