ABSTRACT
MicroRNA-15a-3p (miR-15) acts as tumor-suppressor in different human cancers including osteosarcoma. Nonetheless, the molecular function of miR-15 in osteosarcoma via suppression of cyclin dependent kinase 6 (CDK6) is yet to be studied. The results showed significant downregulation of miR-15 in osteosarcoma tissues and cell lines. Overexpression of miR-15 inhibited the proliferation and colony formation of the MG-63 osteosarcoma cells via induction of apoptosis. Moreover, miR-15 inhibited the migration and invasion of MG-63 osteosarcoma cells. The tumor-suppressive functional role of miR-15 was shown to be exerted via suppression of CDK6. The expression of CDK6 was upregulated in osteosarcoma and its silencing could exert growth inhibitory effects on human osteosarcoma cells. However, overexpression of CDK6 could nullify the tumor-suppressive effects of miR-15 on the MG-63 osteosarcoma cells. Taken together, miR-15 negatively regulates growth, migration and invasion of osteosarcoma cells by targeting CDK6 at post-transcriptional level. These findings suggest the therapeutic potential of miR-15/CDK6 in human osteosarcoma.
Subject(s)
Bone Neoplasms , MicroRNAs , Osteosarcoma , Humans , MicroRNAs/metabolism , Cyclin-Dependent Kinase 6/genetics , Cyclin-Dependent Kinase 6/metabolism , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Cell Proliferation/genetics , Cell Line, Tumor , Osteosarcoma/genetics , Neoplasm Invasiveness/genetics , Cell Movement/genetics , Gene Expression Regulation, NeoplasticABSTRACT
The objective of the study was to investigate the stress changes in the posterior articular surface of the calcaneus following alternation of the calcaneal varus angle in normal calcaneus and discuss the clinical significance of the calcaneal varus angle. Axial view radiographs of 165 volunteers were obtained to measure the calcaneal varus angle of normal calcaneus. A calcaneal model with different varus angle changes (including +2°, +4°, +6°, -2°, -4°, and -6°) was established using Creo 2.0 software. Stress changes at different calcaneal varus angles in the posterior articular surface of the calcaneus under a load of 100 N were measured. Stressed areas in posterior articular facets were slightly fewer following +2°, +4°, and +6° changes in varus angle than in normal varus angles with stress concentering regions moving to the anteromedial aspect of the posterior calcaneal facet. However, stress concentering areas in posterior calcaneal facets following -4° and -6° changes in varus angle obviously moved to the anterior and posterior medial side of posterior calcaneal facets. Stress distribution in the posterior articular surface of the calcaneus varies with the calcaneal varus angle. The decrease in calcaneal varus angle following operative treatment of calcaneal fractures should be controlled within 2°.
