ArticleJournal of experimental & clinical cancer research : CR2020
microRNA-216b enhances cisplatin-induced apoptosis in osteosarcoma MG63 and SaOS-2 cells by binding to JMJD2C and regulating the HIF1α/HES1 signaling axis.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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, 30 citations in OpenAlex.
- Non-coding RNAs in drug and radiation resistance of bone and soft-tissue sarcoma: a systematic review.eLife · 2022Pooled it
- 8-gingerol from Zingiber officinale induces ER stress-mediated ferroptosis and apoptosis in ovarian cancer involving TRPV1 activation.Cell communication and signaling : CCS · 2026Article
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- HES1 in cancer: a key player in tumorigenesis and its prognostic significance.Molecular genetics and genomics : MGG · 2025Review
- Exploratory Analysis of Molecular Subtypes in Early-Stage Osteosarcoma: Identifying Resistance and Optimizing Therapy.Cancers · 2025Article
- Stratifying osteosarcoma patients using an epigenetic modification-related prognostic signature: implications for immunotherapy and chemotherapy selection.Translational cancer research · 2024Article
- Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.Frontiers in pharmacology · 2024Review
- Focal structural variants revealed by whole genome sequencing disrupt the histone demethylase KDM4C in B-cell lymphomas.Haematologica · 2023Article
- Identification of genes contributing to cisplatin resistance in osteosarcoma cells.FEBS open bio · 2023Article
- Curcumol Synergizes with Cisplatin in Osteosarcoma by Inhibiting M2-like Polarization of Tumor-Associated Macrophages.Molecules (Basel, Switzerland) · 2022Article
- Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis.International journal of molecular sciences · 2022Review
- The functional roles of the circRNA/Wnt axis in cancer.Molecular cancer · 2022Review
- MIR600HG sponges miR-125a-5p to regulate glycometabolism and cisplatin resistance of oral squamous cell carcinoma cells via mediating RNF44.Cell death discovery · 2022Article
- Circular RNA_ANKIB1 accelerates chemo-resistance of osteosarcoma via binding microRNA-26b-5p and modulating enhancer of zeste homolog 2.Bioengineered · 2022Article
- MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway.Analytical cellular pathology (Amsterdam) · 2022Article
- Identification of ATG7 as a Regulator of Proferroptosis and Oxidative Stress in Osteosarcoma.Oxidative medicine and cellular longevity · 2022Article
- Correction to: microRNA-216b enhances cisplatin-induced apoptosis in osteosarcoma MG63 and SaOS-2 cells by binding to JMJD2C and regulating the HIF1α/HES1 signaling axis.Journal of experimental & clinical cancer research : CR · 2021Article
- Current Status and Prospects of Clinical Treatment of Osteosarcoma.Technology in cancer research & treatmentReview
- Advances in the Biological Functions and Mechanisms of miRNAs in the Development of Osteosarcoma.Technology in cancer research & treatmentReview
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlthough cisplatin-based chemotherapy represents the standard regimen for osteosarcoma (OS), OS patients often exhibit treatment failure and poor prognosis due to chemoresistance to cisplatin. Emerging research has highlighted the tumor suppressive properties of microRNAs (miRNAs or miRs) in various human cancers via the inhibition of the histone demethylase jumonji domain containing protein 2C (JMJD2C). As a coactivator for hypoxia-inducible factor 1α (HIF1α), JMJD2C targets hairy and enhancer of split-1 (HES1) gene. Hence, the current study aimed to elucidate the role of miR-216b in OS cell cisplatin resistance to identify the underlying mechanism of miR-216b regulating the JMJD2C//HIF1α/HES1 signaling.
methodsTumor and paracancerous tissues were collected from OS patients to determine the expression patterns of miR-216b and JMJD2C. After ectopic expression and knockdown experiments in the OS cells, CCK-8 assay and flow cytometry were employed to determine cell viability and apoptosis. The interaction of miR-216b, JMJD2C, HIF1α and HES1 was subsequently determined by dual luciferase reporter, co-immunoprecipitation (IP) and ChIP-qPCR assays. In vivo experiments were conducted to further verify the role of the miR-216b in the resistance of OS cells to cisplatin.
resultsmiR-216b expression was reduced in the OS tissues, as well as the MG63 and SaOS-2 cells. Heightened miR-216b expression was found to be positively correlated with patient survival, and miR-216b further enhanced cisplatin-induced apoptosis of MG63 and SaOS-2 cells. Mechanistically, miR-216b inhibited JMJD2C expression by binding to its 3'UTR. Through interaction with HIF1α, JMJD2C removed the H3K9 methylation modification at the HES1 promoter region, leading to upregulation of HES1 in vitro. Furthermore, miR-216b was observed to increase the tumor growth in nude mice in the presence of cisplatin treatment. HES1 overexpression weakened the effects of miR-216b in MG63 and SaOS-2 cells and in nude mouse xenografts.
conclusionOverall, miR-216b enhanced the sensitivity of OS cells to cisplatin via downregulation of the JMJD2C/HIF1α/HES1 signaling axis, highlighting the capacity of miR-216b as an adjunct to cisplatin chemotherapy in the treatment of OS.
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