ArticleCell death & disease2018
miR-34a exerts as a key regulator in the dedifferentiation of osteosarcoma via PAI-1-Sox2 axis.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Targeting AKT as a promising strategy for SOX2-positive, chemoresistant osteosarcoma.Bone research · 2025Article
- Osteosarcoma stem cells resist chemotherapy by maintaining mitochondrial dynamic stability via DRP1.International journal of molecular medicine · 2025Article
- Thrombospondin 1 Promotes Cytoskeleton Remodeling, Dedifferentiation, and Pulmonary Metastasis through ITGA1 and ITGA6 in Osteosarcoma.International journal of biological sciences · 2025Article
- Genetic Associations of Plasminogen Activator Inhibitor-1-Related miRNA Variants with Coronary Artery Disease.International journal of molecular sciences · 2024Article
- Characterization of the SARS-CoV-2 Genome 3'-Untranslated Region Interactions with Host MicroRNAs.ACS omega · 2024Article
- LncRNA HCG18 Promotes Osteosarcoma Cells Proliferation, Migration, and Invasion in by Regulating miR-34a/RUNX2 Pathway.Biochemical genetics · 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
- MiR26-5p inhibits pathological pulmonary microvascular angiogenesis via down-regulating WNT5A.Iranian journal of basic medical sciences · 2023Article
- The Role of Tumor Microenvironment in Regulating the Plasticity of Osteosarcoma Cells.International journal of molecular sciences · 2022Review
- Vascular Niche Facilitates Acquired Drug Resistance to c-Met Inhibitor in Originally Sensitive Osteosarcoma Cells.Cancers · 2022Article
- Small Non-Coding RNAs in Human Cancer.Genes · 2022Review
- Mir-34a: a regulatory hub with versatile functions that controls osteosarcoma networks.Cell cycle (Georgetown, Tex.) · 2022Review
- MiR-659-3p inhibits osteosarcoma progression and metastasis by inhibiting cell proliferation and invasion via targeting SRPK1.BMC cancer · 2022Article
- Biomarkers of Frailty: miRNAs as Common Signatures of Impairment in Cognitive and Physical Domains.Biology · 2022Review
- Upregulation of miR-34a-5p, miR-20a-3p and miR-29a-3p by Onconase in A375 Melanoma Cells Correlates with the Downregulation of Specific Onco-Proteins.International journal of molecular sciences · 2022Article
- The Roles of Noncoding RNAs in the Development of Osteosarcoma Stem Cells and Potential Therapeutic Targets.Frontiers in cell and developmental biology · 2022Review
- TP53 in Biology and Treatment of Osteosarcoma.Cancers · 2021Review
- Adipose-PAS interactions in the context of its localised bio-engineering potential (Review).Biomedical reports · 2021Review
- Adipocyte-Derived Leptin Promotes PAI-1 -Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner.Cancers · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Osteosarcoma (OS) is a malignant bone cancer with severe chromosomal abnormalities and genetic aberrations. Our previous work reported the dedifferentiation of OS, which is related to poor prognosis. However, the molecular mechanism that regulates OS dedifferentiation is still a subject of exploration. Emerging evidence has suggested that microRNAs (miRNAs) are associated with the pathogenesis of OS and could potentially be developed for use as diagnostic biomarkers and therapeutic strategies. In the present study, we intended to illustrate the role of miR-34a in the dedifferentiation of OS. Upregulation of miR-34a was observed while OS cells were induced into stem-like phenotype. Notably, inhibition of miR-34a could promote the reprogramming transition of OS. Further exploration on the downstream network of miR-34a identified that blocking plasminogen activator inhibitor-1 (PAI-1) expression could restrain OS dedifferentiation into cancer stem-like cells by downregulating SRY-related-HMG box (Sox) 2. We also showed that Sox2 overexpression rescued the suppression phenotype driven by PAI-1 inhibition. Conversely, PAI-1 inhibitor (PAI-039) could suppress the upregulation of Sox2 expression caused by miR-34a inhibition. Be applying bone extracellular matrix (BEM)-OS models, we demonstrated the phenotypic heterogeneity of OS cells, consistent with a strong concordance between PAI-1 and Sox2 expression levels. Taken together, our findings proved miR-34a to be a bona fide suppressor involved in the regulation of OS dedifferentiation. Targeting miR-34a or its direct target PAI-1 could offer new strategies for OS treatment.
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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.