ABSTRACT
Recently, many kinds of microRNAs (miRNAs) have been found to play a critical role in progression of osteosarcoma (OS). miR-217 was reported to function as a tumor suppressor in a number of human cancers but its precise mechanism to exert the suppressive role remains to be investigated. In this study, we found that miR-217 was downregulated in OS tissues and its downregulation predicts poor overall survival of OS patients. Importantly, we found that a lower expressed miR-217 in OS cell lines inhibited the cell proliferation and invasion in vitro. By bioinformatic analysis, we found that miR-217 targeted the SET Domain-Containing Protein 8 (SETD8), and there was a negative correlation between them in OS tissues. Furthermore, we found that miR-217 abolished the stimulation effect of SETD8 on cell proliferation and invasion. Taken together, our data provide solid evidence that miR-217 functions as tumor suppressor in OS, and its tumor-suppressive effect is exerted through interaction with SETD8.
Subject(s)
Bone Neoplasms/pathology , Histone-Lysine N-Methyltransferase/metabolism , MicroRNAs/genetics , Osteosarcoma/pathology , Bone Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Invasiveness , Osteosarcoma/genetics , Survival RateABSTRACT
BACKGROUND/AIMS: Osteoarthritis (OA) is characterized by degradation of cartilage, sole cell type of which is chondrocytes. Bone marrow-derived mesenchymal stem cells (BMSCs) possess multipotency and can be directionally differentiated into chondrocytes under stimulation. This study was aimed to explore the possible roles of vitamin D and transforming growth factor-ß1 (TGF-ß1) in the chondrogenic differentiation of BMSCs. METHODS: BMSCs were isolated from femurs and tibias of rats and characterized by flow cytometry. After stimulation with vitamin D, BMSC proliferation and migration were measured by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. Chondrogenic differentiation was estimated through expression levels of specific markers by qRT-PCR and Western blot analysis. After stable transfection, the effects of aberrantly expressed TGF-ß1 on vitamin D-induced alterations, including BMSC viability, migration and chondrogenic differentiation, were all evaluated utilizing CCK-8 assay, Transwell assay, qRT-PCR and Western blot analysis. Finally, the phosphorylation levels of key kinases in the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways were determined by Western blot analysis. RESULTS: Vitamin D remarkably promoted BMSC viability, migration and chondrogenic differentiation. These alterations of BMSCs induced by vitamin D were reinforced by TGF-ß1 overexpression while were reversed by TGF-ß1 silencing. Additionally, the phosphorylation levels of ERK, JNK and c-Jun were enhanced by TGF-ß1 overexpression but were reduced by TGF-ß1 knockdown. CONCLUSION: Vitamin D promoted BMSC proliferation, migration and chondrogenic differentiation. TGF-ß1 might be implicated in the vitamin D-induced alterations of BMSCs through regulating ERK/JNK pathway.
