ArticleOncotarget2016
Circadian clock components RORα and Bmal1 mediate the anti-proliferative effect of MLN4924 in osteosarcoma cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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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
15 citing papers in PubMed, 21 citations in OpenAlex.
- The Common Hallmarks and Interconnected Pathways of Aging, Circadian Rhythms, and Cancer: Implications for Therapeutic Strategies.Research (Washington, D.C.) · 2025Review
- Circadian Effects of Melatonin Receptor-Targeting Molecules In Vitro.International journal of molecular sciences · 2024Article
- The Role of Ubiquitination in Osteosarcoma Development and Therapies.Biomolecules · 2024Review
- Circadian rhythm regulates the function of immune cells and participates in the development of tumors.Cell death discovery · 2024Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Major roles of the circadian clock in cancer.Cancer biology & medicine · 2023Review
- Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo.Biomedicines · 2022Article
- Circadian rhythms and cancers: the intrinsic links and therapeutic potentials.Journal of hematology & oncology · 2022Review
- Review
- IDH1 gene mutation activates Smad signaling molecules to regulate the expression levels of cell cycle and biological rhythm genes in human glioma U87‑MG cells.Molecular medicine reports · 2021Article
- Metabolic rivalry: circadian homeostasis and tumorigenesis.Nature reviews. Cancer · 2020Review
- Small Molecules Targeting Biological Clock; A Novel Prospective for Anti-Cancer Drugs.Molecules (Basel, Switzerland) · 2020Review
- RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway.Frontiers in oncology · 2019Article
- Cryptochrome 2 (CRY2) Suppresses Proliferation and Migration and Regulates Clock Gene Network in Osteosarcoma Cells.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- The MiR-135b-BMAL1-YY1 loop disturbs pancreatic clockwork to promote tumourigenesis and chemoresistance.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anticancer small molecule MLN4924, a Nedd8-activating enzyme (NAE) inhibitor, triggers cell-cycle arrest, apoptosis, and senescence in cancer cells. In this study, we demonstrate that MLN4924 suppresses osteosarcoma cell proliferation by inducing G2/M cell cycle arrest and apoptosis. Our results indicate that MLN4924 stabilizes the retinoid orphan nuclear receptor alpha (RORα) by decreasing its ubiquitination. RNA interference of RORα attenuates the anti-proliferative effect of MLN4924 in U2OS osteosarcoma cells. MLN4924 up-regulates the expression of p21 and Bmal1, two transcriptional targets of RORα. However, p21 plays a minimal role in the anti-proliferative effect of MLN4924 in U2OS osteosarcoma cells. In contrast, Bmal1 suppression by siRNA attenuates the anti-proliferative effect of MLN4924 in U2OS osteosarcoma cells, indicating that the MLN4924-mediated cell growth inhibition is mediated by Bmal1. These results show MLN4924 to be a promising therapeutic agent for the treatment of osteosarcoma and suggest that MLN4924-induced tumor growth inhibition is mediated by the circadian clock components RORα and Bmal1.
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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.