intratibial-osteosarcoma-cell-injection-to-generate-orthotopic

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models

Osteosarcoma is the most common primary bone cancer in children and adolescents, with lungs as the most common metastatic site. The five-year survival ...

merip-qpcr-assay-for-detecting-m6a-modification-levels-specific-rna

MeRIP-qPCR Assay for Detecting m<sup>6</sup>A Modification Levels of Specific RNA in Osteosarcoma Cells

RNA epitranscriptomic modification plays a critical role in the initiation and development of various cancers, among which N6-methyladenosine (m6A) is the ...

colony-formation-assay-detecting-proliferative-capacity-lncrna

Colony Formation Assay Detecting the Proliferative Capacity of LncRNA-knockdown Osteosarcoma Cells

Aberrant long non-coding RNAs (lncRNAs) expression profoundly influences cellular proliferation of osteosarcoma cells, suggesting that they may serve as ...

dot-blot-assay-for-detecting-global-n6-methyladenosine-rna

Dot Blot Assay for Detecting Global N<sup>6</sup>-Methyladenosine RNA Modification Levels

N6-methyladenosine (m&#8310;A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA) and serves as a key regulator of ...

clinical-efficacy-an-innovative-multidimensional-traction-therapy

Clinical Efficacy of an Innovative Multidimensional Traction Therapy in Moderate Adolescent Idiopathic Scoliosis

This protocol aims to determine whether a patient-specific, multidimensional traction (MDT regimen), delivered alongside standard bracing and ...

bawei-aiguning-granules-for-lung-cancer-bone-metastases-randomized

Bawei Aiguning Granules For Lung Cancer Bone Metastases: A Randomized, Double-blind, Placebo-Controlled Trial Protocol With A Representative Case

Bone metastases (BM) frequently lead to skeletal-related events (SREs) and significant pain in lung cancer patients, requiring more effective supportive ...

Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education

Shanghai University of Traditional Chinese Medicine

Ministry of Education

Longhua Hospital, Shanghai University of Traditional Chinese Medicine

 As the leading primary bone cancer in adolescents and children, osteosarcoma patients with metastasis show a five-year-survival-rate of 20-30%, without improvement over the past 30 years. Wnt/β-catenin is important in promoting osteosarcoma development. DKK3 is a Wnt/β-catenin antagonist and predicted to have the specific binding site in 3'-UTR with miR-214-3p.  miR-214-3p and DKK3 levels were investigated in human osteosarcoma tissues and cells by RT-qPCR; the prognostic importance of DKK3 level in osteosarcoma patients was determined with Log-rank test; direct binding between DKK3 with miR-214-3p was identified with targetscan; anti-osteosarcoma mechanism of cantharidin was investigated by miR-214-3p silence/over-expression with or without cantharidin treatment, and nuclear/cytoplasmic protein assay in osteosarcoma cells.  Down-regulated DKK3 indicated poor prognosis of osteosarcoma patients. Up-regulated miR-214-3p promoted proliferation and migration, while suppressed apoptosis of osteosarcoma cells by increasing β-catenin nuclear translocation and LEF1 translation via degradation of DKK3. Cantharidin suppressed viabilities, migration and invasion, while promoted cell cycle arrest and apoptosis in 143B and U-2 OS cells via down-regulating miR-214-3p to up-regulate DKK3, thus inhibited p-GSK-3β expression, β-catenin nuclear translocation and LEF1 translation. Meanwhile, cantharidin inhibited tumor growth in xenograft-bearing mice with 143B cell injection in tibia.  miR-214-3p mediated Wnt/β-catenin/LEF1 signaling activation by targeting DKK3 to promote oncogenesis of osteosarcoma; cantharidin inhibited proliferation and metastasis of osteosarcoma cells via down-regulating miR-214-3p to up-regulate DKK3 and decrease β-catenin nuclear translocation, indicating that cantharidin may be a prospective candidate for osteosarcoma treatment by targeting miR-214-3p/DKK3/β-catenin signaling.

Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation.

Increasing studies have revealed significant associations between  with oncogenesis and prognosis of human cancers; however, pan-cancer analysis has not been reported. Here, we explored the potential carcinogenic function and the association with clinical outcomes of  in 33 different human cancers. The results showed that  was amplified in 31 investigated cancers;  expression was significantly associated with metastasis of six different cancers and significantly associated with the survival of patients in ten different cancers; TOP2A-encoded protein was obviously upregulated in five available cancers; phosphorylated TOP2A protein at S1106 was significantly upregulated in all six available cancers. Moreover,  expression was found to be associated with the cancer-associated immune cell infiltration, including fibroblasts, Tregs, and macrophages. In addition, the Kyoto encyclopedia of genes and genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses revealed a most significant association between  with the Wnt signaling pathway and DNA conformation change. This work provides a comprehensive knowledge of  in different cancers, including carcinogenic function, prognostic values for metastasis, and clinical outcomes.

Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and mA-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of mA-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes.

To investigate the synergistic effects of polyphyllin I (PPI) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.

Polyphyllin I enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth downregulating the Wnt/β-catenin pathway.

ArticleTotal : 6	Year
Publication title Cited by 4	2021
Publication title	2025
Publication title	2026
Publication title	2026
Publication title	2026

Article	Year
Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation. International journal of biological sciences\| PubMed ID: 34326690	2021
Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis. Frontiers in genetics\| PubMed ID: 35873470	2022
Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes. Frontiers in genetics\| PubMed ID: 36824434	2023
Polyphyllin I enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth downregulating the Wnt/β-catenin pathway. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan\| PubMed ID: 38504531	2024

Fulai Zhao

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