ArticleCancer research2015
Targeting the miR-221-222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 88 citations in OpenAlex.
- DTX3 promotes anti-tumor immunity by inducing PD-L1 ubiquitination and is suppressed by p65/miR-222 in bladder cancer.Oncogene · 2026Article
- RNA-Based Therapeutic Strategies in Multiple Myeloma: From Molecular Targets to Delivery and Clinical Translation.International journal of molecular sciences · 2026Review
- Review
- Exploring the role of miR-221/222 in gastrointestinal cancers: implications for innovative therapeutic strategies.Cancer cell international · 2025Review
- Refining precision prognostics in multiple myeloma: loss of miR-221/222 cluster in CD138+ plasma cells results in short-term progression and worse treatment outcome.Blood cancer journal · 2025Article
- Complicated crosstalk between HMGA and non-coding RNAs modulates hallmarks of cancer.Cancer cell international · 2025Review
- An overview of multiple myeloma: A monoclonal plasma cell malignancy's diagnosis, management, and treatment modalities.Saudi journal of biological sciences · 2024Review
- MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications.Biomolecules · 2023Review
- A domino-like localized cascade toehold assembly amplification-based DNA nanowire for microRNA imaging in living cells.Chemical science · 2022Article
- Role of microRNAs and long non‑coding RNAs in glucocorticoid signaling (Review).International journal of molecular medicine · 2022Review
- G6PD promotes cell proliferation and dexamethasone resistance in multiple myeloma via increasing anti-oxidant production and activating Wnt/β-catenin pathway.Experimental hematology & oncology · 2022Article
- MiRNA as a Potential Target for Multiple Myeloma Therapy-Current Knowledge and Perspectives.Journal of personalized medicine · 2022Review
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- miRNA-seq and clinical evaluation in multiple myeloma: miR-181a overexpression predicts short-term disease progression and poor post-treatment outcome.British journal of cancer · 2022Article
- Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins.Genes & development · 2021Article
- MiR-222-3p promotes the proliferation, migration and invasion of papillary thyroid carcinoma cells through targeting SLC4A4.Histology and histopathology · 2021Article
- MicroRNA-221 regulates cell activity and apoptosis in acute lymphoblastic leukemia via regulating PTEN.Experimental and therapeutic medicine · 2021Article
- MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease.Cancers · 2021Review
- miR-221/222 sponge abrogates tamoxifen resistance in ER-positive breast cancer cells through restoring the expression of ERα.Molecular biomedicine · 2021Article
- Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review).International journal of oncology · 2021Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite recent therapeutic advances that have doubled the median survival time of patients with multiple myeloma, intratumor genetic heterogeneity contributes to disease progression and emergence of drug resistance. miRNAs are noncoding small RNAs that play important roles in the regulation of gene expression and have been implicated in cancer progression and drug resistance. We investigated the role of the miR-221-222 family in dexamethasone-induced drug resistance in multiple myeloma using the isogenic cell lines MM1R and MM1S, which represent models of resistance and sensitivity, respectively. Analysis of array comparative genome hybridization data revealed gain of chromosome X regions at band p11.3, wherein the miR-221-222 resides, in resistant MM1R cells but not in sensitive MM1S cells. DNA copy number gains in MM1R cells were associated with increased miR-221-222 expression and downregulation of p53-upregulated modulator of apoptosis (PUMA) as a likely proapoptotic target. We confirmed PUMA mRNA as a direct target of miR-221-222 in MM1S and MM1R cells by both gain-of-function and loss-of-function studies. In addition, miR-221-222 treatment rendered MM1S cells resistant to dexamethasone, whereas anti-miR-221-222 partially restored the dexamethasone sensitivity of MM1R cells. These studies have uncovered a role for miR-221-222 in multiple myeloma drug resistance and suggest a potential therapeutic role for inhibitors of miR-221-222 binding to PUMA mRNA as a means of overcoming dexamethasone resistance in patients. The clinical utility of this approach is predicated on the ability of antisense miR-221-222 to increase survival while reducing tumor burden and is strongly supported by the metastatic propensity of MM1R cells in preclinical mouse xenograft models of multiple myeloma. Moreover, our observation of increased levels of miR-221-222 with decreased PUMA expression in multiple myeloma cells from patients at relapse versus untreated controls suggests an even broader role for miR-221-222 in drug resistance and provides a rationale for the targeting of miR-221-222 as a means of improving patient outcomes.
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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.