ArticleBreast cancer research : BCR2023
MiR-4649-5p acts as a tumor-suppressive microRNA in triple negative breast cancer by direct interaction with PIP5K1C, thereby potentiating growth-inhibitory effects of the AKT inhibitor capivasertib.
Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- PIPKIγ promotes non-homologous end joining through LIG4 to enhance radiotherapy resistance in triple-negative breast cancer.Cell death & disease · 2025Article
- Temporal Effects of Disease Signature Genes and Core Mechanisms in the Hyperacute Phase of Acute Ischemic Stroke: A Bioinformatics Analysis and Experimental Validation.Mediators of inflammation · 2025Article
- Characterization of novel anoikis-related genes as prognostic biomarkers and key determinants of the immune microenvironment in esophageal cancer.Frontiers in immunology · 2025Article
- Harnessing natural compounds to modulate miRNAs in breast cancer therapy.Functional & integrative genomics · 2024Review
- Impact of microRNA variants on PI3K/AKT signaling in triple-negative breast cancer: comprehensive review.Medical oncology (Northwood, London, England) · 2024Review
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundTriple negative breast cancer (TNBC) is a particularly aggressive and difficult-to-treat subtype of breast cancer that requires the development of novel therapeutic strategies. To pave the way for such developments it is essential to characterize new molecular players in TNBC. MicroRNAs (miRNAs) constitute interesting candidates in this regard as they are frequently deregulated in cancer and contribute to numerous aspects of carcinogenesis. METHODS AND
resultsHere, we discovered that miR-4649-5p, a miRNA yet uncharacterized in breast cancer, is associated with better overall survival of TNBC patients. Ectopic upregulation of the otherwise very low endogenous expression levels of miR-4646-5p significantly decreased the growth, proliferation, and migration of TNBC cells. By performing whole transcriptome analysis and physical interaction assays, we were able to identify the phosphatidylinositol phosphate kinase PIP5K1C as a direct target of miR-4649-5p. Downregulation or pharmacologic inhibition of PIP5K1C phenocopied the growth-reducing effects of miR-4649-5p. PIP5K1C is known to play an important role in migration and cell adhesion, and we could furthermore confirm its impact on downstream PI3K/AKT signaling. Combinations of miR-4649-5p upregulation and PIP5K1C or AKT inhibition, using the pharmacologic inhibitors UNC3230 and capivasertib, respectively, showed additive growth-reducing effects in TNBC cells.
conclusionIn summary, miR-4649-5p exerts broad tumor-suppressive effects in TNBC and shows potential for combined therapeutic approaches targeting the PIP5K1C/PI3K/AKT signaling axis.
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