MicroRNA-139 inhibits the proliferation and migration of osteosarcoma cells via targeting forkhead-box P2.

AIMS: Osteosarcoma (OS) is the most common primary bone malignancy that affects adolescents. Although great attention has been paid to the diagnosis of and therapy for OS, the 5-year survival rate of patients with this disease remains poor. MicroRNAs are small non-coding RNAs involved in pathogenesis and progression of human malignancies. MiR-139 has been implicated in several human cancers. However, the role played by miR-139 in pathogenesis of human OS has remained largely unknown. MAIN METHODS: Realtime PCR was used to detect the expression of miR-139. CCK-8, BrdU-ELISA and ApoTox-Glo™ Triplex assay was employed to detect the proliferation and apoptosis of osteosarcoma cells. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis. KEY FINDINGS: The expression of miR-139 was reduced while the expression of forkhead-box P2 (FOXP2) was induced in both OS tissue and cell lines. The reduced level of miR-139 was correlated with tumor size, clinical stage and distant metastasis. Overexpression of miR-139 inhibited the expression of FOXP2, which suppressed cell growth, but induced apoptosis. Further, we confirmed that FOXP2 was a direct target of miR-139 by luciferase reporter assay. Knockdown of FOXP2 resulted in reduced levels of cell proliferation, but increased levels of apoptosis in vitro. SIGNIFICANCE: These findings suggest that miR-139 plays a suppressive role in the regulation of OS cell proliferation and migration via directly targeting FOXP2, which might be a potential clinical diagnostic or predictive biomarker for human OS.

Changes of rabbit meniscus influenced by hyaline cartilage injury of osteoarthritis.

PURPOSE: Osteoarthritis (OA) is a common disease in the elderly population. Most of the previous OA-related researches focused on articular cartilage degeneration, osteophyte formation and synovitis etc. However, the role of the meniscus in these pathological changes has not been given enough attention. The goal of our study was to find the pathological changes of the meniscus in OA knee and determine their relationship. METHOD: 20 months old female Chinese rabbits received either knee damaging operations with articular cartilage scratch method or sham operation randomly on one of their knees. They were sacrificed after 1-6 weeks post-operation. Medial Displacement Index (MDI) for meniscus dislocation, hematoxylin and eosin (HE) for routine histological evaluation, Toluidine blue (TB) stains for evaluating proteoglycans were carried out. Immunohistochemical (IHC) staining was performed with a two-step detection kit. RESULTS: Histological analysis showed chondrocyte clusters around cartilage lesions and moderate loss of proteoglycans in the operation model, as well as MDI increase and all characteristics of OA. High expression of MMP-3 and TIMP-1 also were found in both hyaline cartilage and meniscus. CONCLUSION: Biomechanical and biochemistry environment around the meniscus is altered when OA occur. If meniscus showed degeneration, subluxation and dysfunction, OA would be more severe. Prompt repair or reconstruction of hyaline cartilage in weight bearing area when it injured could prevent meniscus degeneration and subluxation, then prevent the development of OA.

Transforming growth factor-1 promotes the transcriptional activation of plasminogen activator inhibitor type 1 in carcinoma-associated fibroblasts.

Carcinoma-associated fibroblasts (CAFs) play a pivotal role in promoting the growth, invasion and metastasis of tumor cells. However, to date little is known about the oncogenic mechanisms of CAFs. This study aimed to identify the microenvironmental factors involved in tumor development and progression directed by CAFs in liver metastases. Tissue samples collected from 20 patients with colorectal liver metastases were used in this study. Histological and morphological characterization of the samples was performed using hybridization and immunohistological assays. The mRNA expression of α-smooth muscle actin (α-SMA) was measured by northern blotting. The expression of plasminogen activator inhibitor type 1 (PAI-1) was measured by enzyme-linked immunosorbent assay (ELISA). As a result, co-expression of Thy-1 (CD90) and α-SMA was identified in CAFs, while normal liver samples were negative for α-SMA and Thy-1. Compared with epidermal growth factor (EGF) and tumor necrosis factor (TNF) incubation, the expression of α-SMA increased significantly following transforming growth factor-1 (TGF-1) incubation (P<0.05), while platelet-derived growth factor (PDGF) caused a significant suppression of α-SMA expression (P<0.05). PAI-1 expression was significantly lower in unstimulated fibroblasts compared to TGF-1-treated fibroblasts (P<0.01). The levels of PAI-1 transcription were significantly higher in CAFs from the patient samples compared with the healthy controls. Taken together, our findings suggest that CAFs may be important in migration, matrix degradation, invasion and angiogenesis of tumors, and TGF-1 may promote the activation of PAI-1 transcription in CAFs.