Abstract
Osteosarcoma (OS) is an aggressive malignant neoplasm that commonly occurs in adults and adolescents. The objectives of this work were to verify the role of microRNA- (miR-) 135a in OS and determine whether it can regulate the growth and cellular migration of OS by targeting mothers against decapentaplegic homolog 2 (SMAD2). miR-135a and SMAD2 mRNA expression levels were measured using reverse transcription-quantitative PCR (RT-qPCR). Proliferation and migration of cells were studied using the Cell Counting Kit-8, EdU staining, and transwell invasion experiment. Additionally, a dual-luciferase reporter experiment was used to investigate the possible relationship between miR-135a and SMAD2's 3'-UTR. Immunohistochemistry was utilized to examine the expressions of SMAD2 and Ki67 in mouse tumor tissues to determine the influence of miR-135a on cancer progression in vivo. miR-135a was shown to be elevated in OS tissue samples as well as five cell lines. High expression levels of miR-135a were correlated with poor prognosis of OS patients. Cellular proliferation and migration were promoted by the upregulation of miR-135a with miR mimics; however, this effect was inhibited by SMAD2 overexpression. miR-135a was also shown to directly target the 3'-UTR of SMAD2. Animal experiments also demonstrated that miR-135a downregulation had an inhibitory effect on tumor growth in vivo. High expression levels of miR-135a promoted transplanted tumor development in vivo and the proliferation and migration of OS cells by targeting SMAD2. In summary, miR-135a may be a prospective therapeutic target for OS in the future.