ReferenceID 4832
Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation
Int J Biol Sci
Background: 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/beta-catenin is
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Record Fields
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- Reference Id
- 4832
- Evidence Id
- 21422
- Core Evidence Id
- 21422
- Source Reference Id
- 2916
- Herb2 Reference Id
- HBREF003713
- Subject Paper Key
- HBIN019611_34326690
- Pubmed Id
- 34326690
- Doi
- 10.7150/ijbs.51638
- Paper Title
- Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation
- Paper Abstract
- Background: 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/beta-catenin is important in promoting osteosarcoma development. DKK3 is a Wnt/beta-catenin antagonist and predicted to have the specific binding site in 3'-UTR with miR-214-3p. Methods: 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. Results: 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 beta-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-3beta expression, beta-catenin nuclear translocation and LEF1 translation. Meanwhile, cantharidin inhibited tumor growth in xenograft-bearing mice with 143B cell injection in tibia. Conclusion: miR-214-3p mediated Wnt/beta-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 beta-catenin nuclear translocation, indicating that cantharidin may be a prospective candidate for osteosarcoma treatment by targeting miR-214-3p/DKK3/beta-catenin signaling.
- Journal
- Int J Biol Sci
- Publish Year
- 2021
- Experiment Subject
- mouse; human; patient; 143b and u-2 os cells; children
- Experiment Type
- Cell Experiment
- Phenotype Related
- Tumor; Osteosarcoma; Bone Cancer
- Paper Title Cn
- Paper Title En
- Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation
- Bilingual Status
- semi_complete