Osteosarcoma (OS) is identified as the most commonly diagnosed malignant cancer of bone, and has approximately three million new cases annually. miR-26a plays an important role in the development of various types of cancer. We investigated whether miR-26a can regulate the migration and invasion of OS by targeting high-mobility group A1 HMGA1. Western blot analysis was used to identify the changes of protein levels. Reverse transcription-quantitative PCR was used to test expression levels of genes and miR-26a. Luciferase reporter assay was used to test the specific target gene of miR-26a. Transwell assay was employed to determine the migration and invasion of OS cell lines. In the present study, miRNA-26a was frequently downregulated in OS tissues and cells. Overexpression of miR-26a inhibited cell migration and invasion in vitro. In addition, miR-26a downregulated HMGA1 by targeting its 3′-UTR and knockdown of HMGA1 significantly suppressed the migration and invasion of two osteosarcoma cell lines in vitro. miR-26a suppressed the migration and invasion of OS cells by targeting HMGA1, suggesting that miR-26a/HMGA1 axis provides a new prospective therapeutic strategy for OS.

BackgroundThe transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in promoting tumor growth. TGF-β1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-β1 inhibits tumorigenesis of ATC cells.Material/MethodsEffects of TGF-β1 stimulation or TGF-β1 inhibition by small interfering RNA (TGF-β1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-β1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-β1 inhibition on tumorigenesis development.ResultsTGF-β1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-β1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-β1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-β1siRNA requires pERK1/2 inhibition. TGF-β1 shRNA inhibited tumor growth in vivo.ConclusionsTherapies targeting the TGF-β1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-κB/PUMA signaling.

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