ArticlePloS one2014
In vitro and in vivo activity of a novel locked nucleic acid (LNA)-inhibitor-miR-221 against multiple myeloma cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04811898 (A Dose Escalation Phase I Study of LNA-i-miR-221 for the Treatment of Refractory Multiple Myeloma and Advanced Solid Tumors), which is not on this map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Dose Escalation Phase I Study of LNA-i-miR-221 for the Treatment of Refractory Multiple Myeloma and Advanced Solid Tumors
Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- A systematic review of non-coding RNA therapeutics in early clinical trials: a new perspective against cancer.Journal of translational medicine · 2024Pooled it
- Targeting lncRNAs to Overcome Cancer Therapy Resistance: Advances in RNA Therapeutics and Delivery Strategies.Cancers · 2026Review
- Deciphering epigenetic crosstalk in multiple myeloma pathogenesis and treatment.Clinical epigenetics · 2026Review
- Article
- miRNA-driven cancer cell plasticity, tolerance and therapy resistance: lessons from melanoma.Molecular cancer · 2026Review
- MicroRNA in cancer therapy: breakthroughs and challenges in early clinical applications.Journal of experimental & clinical cancer research : CR · 2025Review
- LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.Molecular therapy. Nucleic acids · 2024Article
- Scaling approaches for the prediction of human clearance of LNA-i-mir-221: A retrospective validation.Current research in pharmacology and drug discovery · 2024Article
- Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.Journal of hematology & oncology · 2023Article
- Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19.Acta pharmacologica Sinica · 2022Review
- Thyclotides, tetrahydrofuran-modified peptide nucleic acids that efficiently penetrate cells and inhibit microRNA-21.Nucleic acids research · 2022Article
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- Roles of miRNA dysregulation in the pathogenesis of multiple myeloma.Cancer gene therapy · 2021Review
- Cryo-EM and antisense targeting of the 28-kDa frameshift stimulation element from the SARS-CoV-2 RNA genome.Nature structural & molecular biology · 2021Article
- miR-22 Modulates Lenalidomide Activity by Counteracting MYC Addiction in Multiple Myeloma.Cancers · 2021Article
- Review
- Non-coding RNAs and potential therapeutic targeting in cancer.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides.Molecules (Basel, Switzerland) · 2020Review
- Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology.Non-coding RNA · 2020Review
- Strategies to Modulate MicroRNA Functions for the Treatment of Cancer or Organ Injury.Pharmacological reviews · 2020Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimThe miR-221/222 cluster is upregulated in malignant plasma cells from multiple myeloma (MM) patients harboring the t(4;14) translocation. We previously reported that silencing of miR-221/222 by an antisense oligonucleotide induces anti-MM activity and upregulates canonical miR-221/222 targets. The in vivo anti-tumor activity occurred when miR-221/222 inhibitors were delivered directly into MM xenografts. The aim of the present study was to evaluate the anti-MM activity of a novel phosphorothioate modified backbone 13-mer locked nucleic acid (LNA)-Inhibitor-miR-221 (LNA-i-miR-221) specifically designed for systemic delivery.
methodsIn vitro anti-MM activity of LNA-i-miR-221 was evaluated by cell proliferation and BrdU uptake assays. In vivo studies were performed with non-obese diabetic/severe combined immunodeficient (NOD.SCID) mice bearing t(4;14) MM xenografts, which were intraperitoneally or intravenously treated with naked LNA-i-miR-221. RNA extracts from retrieved tumors were analyzed for miR-221 levels and modulation of canonical targets expression. H&E staining and immunohistochemistry were performed on retrieved tumors and mouse vital organs.
resultsIn vitro, LNA-i-miR-221 exerted strong antagonistic activity against miR-221 and induced upregulation of the endogenous target p27Kip1. It had a marked anti-proliferative effect on t(4;14)-translocated MM cells but not on MM cells not carrying the translocation and not overexpressing miR-221. In vivo, systemic treatment with LNA-i-miR-221 triggered significant anti-tumor activity against t(4;14) MM xenografts; it also induced miR-221 downregulation, upregulated p27Kip1 and reduced Ki-67. No behavioral changes or organ-related toxicity were observed in mice as a consequence of treatments.
conclusionsLNA-i-miR-221 is a highly stable, effective agent against t(4;14) MM cells, and is suitable for systemic use. These data provide the rationale for the clinical development of LNA-i-miR-221 for the treatment of MM.
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