ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
MicroRNA-215-5p Treatment Suppresses Mesothelioma Progression via the MDM2-p53-Signaling Axis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- microRNA-497-5p-based screening identifies a novel synthetic lethal-type interaction via PKMYT1 and WEE1 in pleural mesothelioma.Molecular therapy. Nucleic acids · 2025Article
- Review
- Molecular Mechanisms of Tumor Progression and Novel Therapeutic and Diagnostic Strategies in Mesothelioma.International journal of molecular sciences · 2025Review
- DDP Induced Cytotoxicity through miR-215-5p/COL5A1/FSTL1 Axis to Regulate Autophagy in Lung Adenocarcinoma Cells.Current pharmaceutical biotechnology · 2025Article
- EIF3M as a pan-cancer biomarker: prognostic significance and immune infiltration association.Frontiers in molecular biosciences · 2025Article
- Kinetically Controlled Polyelectrolyte Complex Assembly of microRNA-Peptide Nanoparticles toward Treating Mesothelioma.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- Targeting FAcilitates Chromatin Transcription complex inhibits pleural mesothelioma and enhances immunotherapy.Journal of experimental & clinical cancer research : CR · 2023Article
- Omics Overview of the SPARC Gene in Mesothelioma.Biomolecules · 2023Review
- Unlocking the potential of RNA-based therapeutics in the lung: current status and future directions.Frontiers in genetics · 2023Review
- Hypoxia-induced miR-653 enhances colorectal cancer progression by targeting circSETD3/KLF6 axis.Journal of Cancer · 2023Article
- Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma.International journal of molecular sciences · 2022Review
- Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.Virchows Archiv : an international journal of pathology · 2022Article
- Establishment and validation of a novel immune-related prognostic signature in malignant pleural mesothelioma.Annals of translational medicine · 2022Article
- Promising therapeutic potential of tumor suppressor microRNAs for malignant pleural mesothelioma.Journal of cancer metastasis and treatment · 2022Article
- Current State of Pleural-Directed Adjuncts Against Malignant Pleural Mesothelioma.Frontiers in oncology · 2022Review
- LAMC1-mediated preadipocytes differentiation promoted peritoneum pre-metastatic niche formation and gastric cancer metastasis.International journal of biological sciences · 2022Article
- Barriers in systemic delivery and preclinical testing of synthetic microRNAs in animal models: an experimental study on miR-215-5p mimic.Physiological research · 2021Article
- MicroRNA-206 suppresses mesothelioma progression via the Ras signaling axis.Molecular therapy. Nucleic acids · 2021Article
- Mouse models for mesothelioma drug discovery and development.Expert opinion on drug discovery · 2021Review
- Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1.Molecular cancer · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Malignant pleural mesothelioma (MPM) is an incurable, aggressive neoplasm with distinctive features, including preservation of wild-type p53, irrespective of histologic subtype. We posited that this consistent molecular characteristic represents an underexploited therapeutic target that can be approached by leveraging biologic effects of microRNA (miRNA). The Cancer Genome Atlas was surveyed to identify p53-responsive prognostic miRNA(s) in MPM. Using patient samples, in vitro MPM cell lines, and murine tumor xenograft models, we verified specific gene pathways targeted by these miRNAs, and we examined their therapeutic effects. miR-215-5p is a poor prognosis miRNA downregulated in MPM tissues, which has not been recognized previously. When miR-215-5p was ectopically re-expressed in MPM cells and delivered in vivo to tumor xenografts, it exerted significant cell killing by activating p53 function and inducing apoptosis. The mechanistic basis for this effect is due to combinatorial effects of a positive feedback loop of miR-215-MDM2-p53 signaling, additional mouse double minute 2 (MDM2)-p53 positive feedback loop(s) with other miRNAs such as miR-145-5p, and suppression of diverse gene targets associated with cell cycle dynamics not previously drug treatable in MPM clinical studies. Our results suggest a potential pathophysiologic role for and therapeutic significance of miR-215-5p in MPM.
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