ArticleCell death & disease2021
Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Integrative bioinformatics and molecular simulations identify HMGB3 as a key immune modulator in triple negative breast cancer.Discover oncology · 2026Article
- Mesenchymal stem cell-derived extracellular vesicle therapy in breast cancer: A systematic review and meta-analysis ofMolecular therapy. Oncology · 2026Review
- Engineering MSC-exosomes for diabetic bone regeneration: from mechanism to delivery.Stem cell research & therapy · 2026Review
- Pro-tumorigenic effects and therapeutic implications of mesenchymal stem cell-derived exosomes under hypoxic conditions: a systematic review.Discover oncology · 2026Review
- Unraveling Let-7f in oncology: a tumor suppressor with emerging clinical significance.Frontiers in cell and developmental biology · 2026Review
- CRISPR/Cas9 in cancer therapy: clinical translation, mechanistic strategies, and therapeutic directions.Frontiers in oncology · 2026Review
- Mesenchymal Stromal/Stem Cells (MSCs) in Cancer Therapy: Advanced Therapeutic Strategies Towards Future Clinical Translation.Molecules (Basel, Switzerland) · 2025Review
- miRNAs from mesenchymal-stem-cell-derived extracellular vesicles: Emerging players in regenerative medicine and disease therapy.Molecular therapy. Nucleic acids · 2025Review
- Harnessing engineered mesenchymal stem cell-derived extracellular vesicles for innovative cancer treatments.Stem cell research & therapy · 2025Review
- Molecules interacting with CasL-Like 2 enhances tumor angiogenesis and progression by activating mTOR/HIF1α/VEGF pathway in kidney renal clear cell carcinoma.Scientific reports · 2025Article
- HypoxamiRs: the hidden architects of tissue adaptation in hypoxia.Cell death & disease · 2025Review
- Roles of Mesenchymal Stem Cells in Breast Cancer Therapy: Engineered Stem Cells and Exosomal Cell-Free Based Therapy.Current molecular medicine · 2025Review
- Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α.International journal of molecular sciences · 2024Article
- The role of mesenchymal stem cells in cancer and prospects for their use in cancer therapeutics.MedComm · 2024Review
- Caught in action: how MSCs modulate atherosclerotic plaque.Frontiers in cell and developmental biology · 2024Review
- Hypoxia-Driven Changes in Tumor Microenvironment: Insights into Exosome-Mediated Cell Interactions.International journal of nanomedicine · 2024Review
- Unveiling the multifaceted roles of microRNAs in extracellular vesicles derived from mesenchymal stem cells: implications in tumor progression and therapeutic interventions.Frontiers in pharmacology · 2024Review
- Article
- Thiram, an inhibitor of 11ß-hydroxysteroid dehydrogenase type 2, enhances the inhibitory effects of hydrocortisone in the treatment of osteosarcoma through Wnt/β-catenin pathway.BMC pharmacology & toxicology · 2023Article
- Properties and fate of human mesenchymal stem cells upon miRNA let-7f-promoted recruitment to atherosclerotic plaques.Cardiovascular research · 2023Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.