ArticleFrontiers in oncology2019
Upregulation of miR-214 Induced Radioresistance of Osteosarcoma by Targeting PHLDA2 via PI3K/Akt Signaling.
Article in Frontiers in oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Non-coding RNAs in drug and radiation resistance of bone and soft-tissue sarcoma: a systematic review.eLife · 2022Pooled it
- Matrix type influences embedded patient-derived osteosarcoma organoid invasion and response to treatment.Frontiers in pharmacology · 2026Article
- From conventional to cutting edge: an exploration of osteosarcoma treatments.Medical oncology (Northwood, London, England) · 2025Review
- Epigenetic modification of PHLDA2 is associated with tumor microenvironment and unfavorable outcome of immune checkpoint inhibitor-based therapies in clear cell renal cell carcinoma.European journal of medical research · 2024Article
- miR-124-3p and miR-194-5p regulation of the PI3K/AKT pathway via ROR2 in medulloblastoma progression.Cancer gene therapy · 2024Article
- Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value.Current issues in molecular biology · 2024Article
- Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.Frontiers in oncology · 2023Review
- Mouse mesenchymal stem cell-derived exosomal miR-466f-3p reverses EMT process through inhibiting AKT/GSK3β pathway via c-MET in radiation-induced lung injury.Journal of experimental & clinical cancer research : CR · 2022Article
- Improving the prediction for the response to radiotherapy of clinical tumor samples by using combinatorial model of MicroRNA expression.Frontiers in genetics · 2022Article
- The roles of glycolysis in osteosarcoma.Frontiers in pharmacology · 2022Review
- MicroRNA miR-23b-3p promotes osteosarcoma by targeting ventricular zone expressed PH domain-containing 1 (VEPH1)/phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway.Bioengineered · 2021Article
- Recent Insights into Therapy Resistance in Osteosarcoma.Cancers · 2020Review
- Upregulation of KCNQ1OT1 promotes resistance to stereotactic body radiotherapy in lung adenocarcinoma by inducing ATG5/ATG12-mediated autophagy via miR-372-3p.Cell death & disease · 2020Article
- PHLD Class Proteins: A Family of New Players in the p53 Network.International journal of molecular sciences · 2020Review
- Efficient miRNA Inhibitor with GO-PEI Nanosheets for Osteosarcoma Suppression by Targeting PTEN.International journal of nanomedicine · 2020Article
- Gene Expression Profiling Identifies Akt as a Target for Radiosensitization in Gastric Cancer Cells.Frontiers in oncology · 2020Article
- miRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance.MicroRNA (Shariqah, United Arab Emirates) · 2020Review
- Research Progress of Exosome-Loaded miRNA in Osteosarcoma.Cancer control : journal of the Moffitt Cancer CenterArticle
- Advances in the Biological Functions and Mechanisms of miRNAs in the Development of Osteosarcoma.Technology in cancer research & treatmentReview
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is an aggressive bone tumor with high resistance to radiotherapy. Pleckstrin homology-like domain family A member 2 (PHLDA2) displays low expression in human osteosarcoma as a proapoptosis factor. miRNAs have been shown to be important in modulating translation and therapeutic responsiveness in solid tumors. Herein, we used luciferase assay to show that miR-214 downregulates the PHLDA2 expression by targeting its 3'-untranslated region (UTR). A high level of miR-214 was identified in tumor tissues from 30 osteosarcoma patients via qPCR analysis, associated positively with lung metastasis. Ectopic expression miR-214 enhanced radioresistance in osteosarcoma cells, with decreased IR-induced apoptosis. Moreover, the depletion of miR-214 enhanced radiosensitivity in both osteosarcoma cells and mouse xenograft models. Importantly, we showed that miR-214 regulated the activation of phosphatidylinositol-3-kinase/Akt signaling pathway by inhibiting PHLDA2. Finally, the introduction of PHLDA2 cDNA lacking the 3'-UTR or treatment with Akt inhibitor LY294002 partially abrogated miR-214-induced radioresistance. In summary, our results reveal that the upregulation of miR-214 as a frequent event in osteosarcoma contributes to radioresistance by regulating the PHLDA2/Akt pathway. The miR-214/PHLDA2/Akt axis provides a new avenue toward understanding the mechanism of radiosensitivity and may be a potential target for osteosarcoma intervention.
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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.