ArticlePloS one2013
MiR-221/222 target the DNA methyltransferase MGMT in glioma cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- Investigating glioblastoma chemoresistance: a meta-analysis of microRNA signatures and gene networks.Journal of neuro-oncology · 2025Pooled it
- Plasma miR-221/222 Family as Novel Descriptive and Prognostic Biomarkers for Glioma.Molecular neurobiology · 2016Pooled it
- Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III.Molecular oncology · 2014Trial
- Methylation of DACT2 promotes papillary thyroid cancer metastasis by activating Wnt signaling.PloS one · 2014Trial
- The Role of Noncoding RNA in MGMT-Positive Glioblastoma: A Narrative Review.Cancer medicine · 2026Review
- Role of non-coding RNAs in OOncology letters · 2026Review
- Temozolomide-induced senescent glioblastoma cells acquire sensitivity to TRAIL death receptor 5-mediated apoptosis.Medical oncology (Northwood, London, England) · 2025Article
- Fibroblasts activated by miRs-185-5p, miR-652-5p, and miR-1246 shape the tumor microenvironment in triple-negative breast cancer via PATZ1 downregulation.Cellular and molecular life sciences : CMLS · 2025Article
- miRNAs and related genetic biomarkers according to the WHO glioma classification: From diagnosis to future therapeutic targets.Non-coding RNA research · 2024Review
- The Versatile Attributes of MGMT: Its Repair Mechanism, Crosstalk with Other DNA Repair Pathways, and Its Role in Cancer.Cancers · 2024Review
- Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review.Cancer reports (Hoboken, N.J.) · 2023Review
- Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach.Cancers · 2023Article
- Review
- Exosomal microRNA-222-3p increases UVB sensitivity of lens epithelium cells by suppressing MGMT.International ophthalmology · 2023Article
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- Emerging role of miRNAs as liquid biopsy markers for prediction of glioblastoma multiforme prognosis.Journal of molecular neuroscience : MN · 2021Article
- Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma Patients Treated with Postoperative Radiotherapy.International journal of molecular sciences · 2021Article
- Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Review
- Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma multiforme (GBM) is one of the most deadly types of cancer. To date, the best clinical approach for treatment is based on administration of temozolomide (TMZ) in combination with radiotherapy. Much evidence suggests that the intracellular level of the alkylating enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) impacts response to TMZ in GBM patients. MGMT expression is regulated by the methylation of its promoter. However, evidence indicates that this is not the only regulatory mechanism present. Here, we describe a hitherto unknown microRNA-mediated mechanism of MGMT expression regulation. We show that miR-221 and miR-222 are upregulated in GMB patients and that these paralogues target MGMT mRNA, inducing greater TMZ-mediated cell death. However, miR-221/miR-222 also increase DNA damage and, thus, chromosomal rearrangements. Indeed, miR-221 overexpression in glioma cells led to an increase in markers of DNA damage, an effect rescued by re-expression of MGMT. Thus, chronic miR-221/222-mediated MGMT downregulation may render cells unable to repair genetic damage. This, associated also to miR-221/222 oncogenic potential, may poor GBM prognosis.
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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.