ArticleCell death & disease2017
Silencing NKG2D ligand-targeting miRNAs enhances natural killer cell-mediated cytotoxicity in breast cancer.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression.Frontiers in immunology · 2021Pooled it
- Targeting the MICA/B-NKG2D axis in cancer: from molecular structure to immunotherapeutic strategies-a narrative review.Translational cancer research · 2026Review
- Epstein-Barr virus and human MiRNAs crosstalk: orchestrating latency, lytic cycle, and immune system modulation.Folia microbiologica · 2026Review
- NKGD2 Ligands (NKG2DLs) in Breast Cancer: In Silico Analysis and Narrative Review.International journal of molecular sciences · 2026Review
- ULBP1 is a prognostic biomarker associated with immune suppression in breast cancer.Frontiers in oncology · 2026Article
- MicroRNA-mediated regulation of natural killer cells development, effector functions, and antitumor responses.Cancer cell international · 2025Review
- The Metabolic Regulation of the NKG2D-Positive NK and T Cells and Their Role in Disease Progression.Biomolecules · 2025Review
- Epigenetic modulation elicits an NK cell-mediated immune response in urothelial carcinoma.Molecular medicine (Cambridge, Mass.) · 2025Article
- Resveratrol contributes to NK cell-mediated breast cancer cytotoxicity by upregulating ULBP2 through miR-17-5p downmodulation and activation of MINK1/JNK/c-Jun signaling.Frontiers in immunology · 2025Article
- Non-coding RNAs as therapeutic targets in cancer and its clinical application.Journal of pharmaceutical analysis · 2024Review
- Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome.International journal of molecular sciences · 2024Article
- Integrated analysis of diverse cancer types reveals a breast cancer-specific serum miRNA biomarker through relative expression orderings analysis.Breast cancer research and treatment · 2024Article
- Novel role of immune-related non-coding RNAs as potential biomarkers regulating tumour immunoresponse via MICA/NKG2D pathway.Biomarker research · 2023Review
- Epigenetic regulation and therapeutic targets in the tumor microenvironment.Molecular biomedicine · 2023Review
- Article
- Suppression of CD56Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2023Article
- Impact of MICA 3'UTR allelic variability on miRNA binding prediction, a bioinformatic approach.Frontiers in genetics · 2023Article
- Killer instincts: natural killer cells as multifactorial cancer immunotherapy.Frontiers in immunology · 2023Review
- Epigenetic modulation of antitumor immunity and immunotherapy response in breast cancer: biological mechanisms and clinical implications.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DLs). NKG2DLs are expressed on malignant cells and sensitize them to early elimination by cytotoxic lymphocytes. We investigated the clinical importance of NKG2DLs and the mechanism of NKG2DL regulation in breast cancer (BC). Among the NKG2DLs MICA/B and ULBP1/2/3, the expression levels of MICA/B in BC tissues were inversely associated with the Tumor Node Metastasis stage. We first found that the high expression of MICB, but not MICA, was an independent prognostic factor for overall survival in patients with BC. Investigation into the mechanism revealed that a group of microRNAs (miRNAs) belonging to the miR-17-92 cluster, especially miR-20a, decreased the expression of ULBP2 and MICA/B. These miRNAs downregulated the expression of MICA/B by targeting the MICA/B 3'-untranslated region and downregulated ULBP2 by inhibiting the MAPK/ERK signaling pathway. Functional analysis showed that the silencing of NKG2DL-targeting miRNAs in BC cells increased NK cell-mediated cytotoxicity in vitro and inhibited immune escape in vivo. In addition, histone deacetylase inhibitors (HDACis) increased NKG2DL expression in BC cells by inhibiting members of the miR-17-92 cluster. Thus, targeting miRNAs with antisense inhibitors or HDACis may represent a novel approach for increasing the immunogenicity of BC.
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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.