ArticleCancer medicine2016
PAI-1, a target gene of miR-143, regulates invasion and metastasis by upregulating MMP-13 expression of human osteosarcoma.
Article in Cancer medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 76 citations in OpenAlex.
- Diverse roles of SERPINE1 in regulating cellular proliferation and invasion.International journal of oncology · 2026Article
- Biomarkers of prognosis and pazopanib response in soft tissue sarcoma: An exploratory analysis.Therapeutic advances in medical oncology · 2026Article
- PAI-1: A Key Signal at the Crossroads of Stem Cell Differentiation and Senescence.International journal of molecular sciences · 2025Review
- Establishment and Characterization of OS-MET-R-092: A Novel Patient-Derived Cell Culture from an Osteosarcoma Bone Metastasis.International journal of molecular sciences · 2025Article
- Regulation of matrix metalloproteinase-13 in cancer: Signaling pathways and non-coding RNAs in tumor progression and therapeutic targeting.World journal of clinical oncology · 2025Review
- Genetic Associations of Plasminogen Activator Inhibitor-1-Related miRNA Variants with Coronary Artery Disease.International journal of molecular sciences · 2024Article
- Effect of Spicatoside a on Anti-Osteosarcoma MG63 Cells through Reactive Oxygen Species Generation and the Inhibition of the PI3K-AKT-mTOR Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Vitexicarpin Induces Apoptosis and Inhibits Metastatic Properties via the AKT-PRAS40 Pathway in Human Osteosarcoma.International journal of molecular sciences · 2024Article
- Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas.Cell death discovery · 2024Article
- Single-cell RNA sequencing reveals SERPINE1-expressing CAFs remodelling tumour microenvironment in recurrent osteosarcoma.Clinical and translational medicine · 2024Article
- Selenium enhances photodynamic therapy of C-phycocyanin against lung cancer via dual regulation of cytotoxicity and antioxidant activity.Acta biochimica et biophysica Sinica · 2023Article
- PBMC MicroRNAs: Promising Biomarkers for the Differential Diagnosis of COVID-19 Patients with Abnormal Coagulation Indices.Current microbiology · 2023Article
- Posttranscriptional Regulation of the Plasminogen Activation System by Non-Coding RNA in Cancer.International journal of molecular sciences · 2023Review
- Profiling of Multiple Matrix Metalloproteinases Activities in the Progression of Osteosarcoma by Peptide Microarray-Based Fluorescence Assay on Polymer Brush-Coated Zinc Oxide Nanorod Substrate.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Hsa_circ_0001982 promotes the proliferation, invasion, and multidrug resistance of osteosarcoma cells.Journal of clinical laboratory analysis · 2022Article
- MicroRNA-143 expression inhibits the growth and the invasion of osteosarcoma.Journal of orthopaedic surgery and research · 2022Review
- SIX5-activated LINC01468 promotes lung adenocarcinoma progression by recruiting SERBP1 to regulate SERPINE1 mRNA stability and recruiting USP5 to facilitate PAI1 protein deubiquitylation.Cell death & disease · 2022Article
- The anti-cancer role of microRNA-143 in papillary thyroid carcinoma by targeting high mobility group AT-hook 2.Bioengineered · 2022Article
- Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets.Cancers · 2022Review
- Osteosarcoma tumor microenvironment: the key for the successful development of biologically relevant 3D in vitro models.In vitro models · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite recent improvements in the therapy for osteosarcoma, 30-40% of osteosarcoma patients die of this disease, mainly due to its lung metastasis. We have previously reported that intravenous injection of miR-143 significantly suppresses lung metastasis of human osteosarcoma cells (143B) in a mouse model. In this study, we examined the biological role and mechanism of miR-143 in the metastasis of human osteosarcoma cells. We identified plasminogen activator inhibitor-1 (PAI-1) as a direct target gene of miR-143. To determine the role of PAI-1 in human osteosarcoma cells, siRNA was transfected into 143B cells for knockdown of PAI-1 expression. An in vitro study showed that downregulation of PAI-1 suppressed cell invasion activity, but not proliferation. Moreover, injection of PAI-1 siRNA into a primary lesion in the osteosarcoma mouse model inhibited lung metastasis compared to control siRNA-injected mice, without influencing the proliferative activity of the tumor cells. Subsequent examination using 143B cells revealed that knockdown of PAI-1 expression resulted in downregulation of the expression and secretion of matrix metalloproteinase-13 (MMP-13), which is also a target gene of miR-143 and a proteolytic enzyme that regulates tumor-induced osteolysis. Immunohistochemical analysis using clinical samples showed that higher miR-143 expressing cases showed poor expression of PAI-1 in the primary tumor cells. All such cases belonged to the lung metastasis-negative group. Moreover, the frequency of lung metastasis-positive cases was significantly higher in PAI-1 and MMP-13 double-positive cases than in PAI-1 or MMP-13 single-positive or double-negative cases (P < 0.05). These results indicated that PAI-1, a target gene of miR-143, regulates invasion and lung metastasis via enhancement of MMP-13 expression and secretion in human osteosarcoma cells, suggesting that these molecules could be potential therapeutic target genes for preventing lung metastasis in osteosarcoma patients.
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