ArticleMolecular oncology2017
CNOT1 cooperates with LMNA to aggravate osteosarcoma tumorigenesis through the Hedgehog signaling pathway.
Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Lamin A/C as a Molecular Link Between Nuclear Organization, Chromatin Dynamics, and Tumor Progression.Cells · 2026Review
- Lamins' role in osteosarcoma.Frontiers in cell and developmental biology · 2026Review
- Post-transcriptional dynamics and RNA homeostasis in autophagy and cancer.Cell death and differentiation · 2025Review
- The paradoxical role of stem cells in osteosarcoma: from pathogenesis to therapeutic breakthroughs.Frontiers in oncology · 2025Review
- Gene regulatory networks reveal sex difference in lung adenocarcinoma.Biology of sex differences · 2024Article
- The OSR9 Regimen: A New Augmentation Strategy for Osteosarcoma Treatment Using Nine Older Drugs from General Medicine to Inhibit Growth Drive.International journal of molecular sciences · 2023Review
- Gene regulatory Networks Reveal Sex Difference in Lung Adenocarcinoma.bioRxiv : the preprint server for biology · 2023Article
- Disruption of the Mammalian Ccr4-Not Complex Contributes to Transcription-Mediated Genome Instability.Cells · 2023Article
- Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers.International journal of molecular sciences · 2023Review
- EVI2B Is a Prognostic Biomarker and Is Correlated with Monocyte and Macrophage Infiltration in Osteosarcoma Based on an Integrative Analysis.Biomolecules · 2023Article
- Integrative profiling analysis reveals prognostic significance, molecular characteristics, and tumor immunity of angiogenesis-related genes in soft tissue sarcoma.Frontiers in immunology · 2023Article
- A novel necroptosis-related lncRNAs signature effectively predicts the prognosis for osteosarcoma and is associated with immunity.Frontiers in pharmacology · 2022Article
- HMGB1 overexpression promotes a malignant phenotype and radioresistance in ESCC.Journal of Cancer · 2022Article
- Identification of Common Oncogenic Genes and Pathways Both in Osteosarcoma and Ewing's Sarcoma Using Bioinformatics Analysis.Journal of immunology research · 2022Article
- Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases.Frontiers in oncology · 2022Review
- Pharmacological inhibition of HDAC1/3-interacting proteins induced morphological changes, and hindered the cell proliferation and migration of hepatocellular carcinoma cells.Environmental science and pollution research international · 2021Article
- Article
- A Novel Predictive Model Associated with Osteosarcoma Metastasis.Cancer management and research · 2021Article
- Review
- A CCR4-NOT Transcription Complex, Subunit 1, CNOT1, Variant Associated with Holoprosencephaly.American journal of human genetics · 2019Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While treatments for childhood osteosarcoma have improved, the overall survival for this common type of bone cancer has not changed for three decades, and thus, new targets for therapeutic development are needed. To identify tumor-related proteins in osteosarcoma, we used isobaric tags in a relative and absolute quantitation proteomic approach to analyze the differentially expressed proteins between osteosarcoma cells and human osteoblastic cells. Through clinical screening and functional evaluation, CCR4-NOT transcription complex subunit 1 (CNOT1) correlated with the growth of osteosarcoma cells. To date, the mechanisms and regulatory roles of CNOT1 in tumors, including osteosarcoma, remain largely elusive. Here, we present evidence that knockdown of CNOT1 inhibits the growth of osteosarcoma in vitro and in vivo. Mechanistically, we observed that CNOT1 interacted with LMNA (lamin A) and functioned as a positive regulator of this intermediate filament protein. The RNA-seq analysis revealed that CNOT1 depletion inhibited the Hedgehog signaling pathway in osteosarcoma cells. A rescue study showed that the decreased growth of osteosarcoma cells and inhibition of the Hedgehog signaling pathway by CNOT1 depletion were reversed by LMNA overexpression, indicating that the activity of CNOT1 was LMNA dependent. Notably, the CNOT1 expression was significantly associated with tumor recurrence, Enneking stage, and poor survival in patients with osteosarcoma. Examination of clinical samples confirmed that CNOT1 expression positively correlated with LMNA protein expression. Taken together, these results suggest that the CNOT1-LMNA-Hedgehog signaling pathway axis exerts an oncogenic role in osteosarcoma progression, which could be a potential target for gene therapy.
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