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MicroRNAs (miRNAs/miRs) are short non-coding RNAs (between 20 and 22 nucleotides) that regulate gene expression by binding to the 3'-untranslated region of target mRNA, and preventing protein translation or inducing mRNA destabilization. miRNAs are predicted to target ~60% of all mRNAs, therefore providing a marked degree of regulation of a number of cellular processes. In the present study, the expression of miR-548c-3p was determined by reverse transcription-quantitative polymerase chain reaction analysis and demonstrated to be markedly downregulated in clinical malignant glioma tissues and the glioma T98G cell line compared with normal human brain tissue. Transfection of miR-548c-3p inhibited cell proliferation by inducing G1 cell cycle arrest and also inhibited the migration of the T98G cells in vitro. Furthermore, a bioinformatic algorithm and a luciferase reporter assay identified proto-oncogene c-Myb (c-Myb) as a potential direct target of miR-548c-3p. Further experiments demonstrated that the inhibition of c-Myb by miR-548c-3p partially mediated the antitumor effect of miR-548c-3p. The results of the present study provide the novel insight that miR-548c-3p inhibits glioma tumorigenesis by targeting c-Myb. Therefore, miR-548c-3p may contribute to the development of improved glioma treatment. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) represents a major endpoint of chronic liver diseases and is the third leading cause of cancer-related mortality. Long intergenic non-coding RNA-integrin subunit ß1 ITGB1 (linc-ITGB1) is a novel long non-coding RNA, which is implicated in the development and progression of human tumors. However, its involvement in hepatocarcinogenesis remains to be elucidated. In the present study, the specific roles of linc-ITGB1 on cell proliferation and metastasis in HCC were investigated. It was initially observed that the expression of linc-ITGB1 was significantly elevated in 30 cases of clinical HCC tissues relative to their adjacent non-cancerous tissues. Expression of linc-ITGB1 was particularly elevated in the highly invasive cell line, HCCLM3. Knockdown of linc-ITGB1 in HCCLM3 cells using a specific short hairpin RNA decreased cell viability and colony formation in vitro. In addition, cell cycle analysis demonstrated that linc-ITGB1-depleted cells accumulated in the G0/G1 phase. HCCLM3 cells with linc-ITGB1 depletion exhibited significantly decreased migration and invasion abilities, when compared with control cells (P<0.05). These data suggest that linc-ITGB1 promotes HCC progression by inducing cell-cycle arrest. Therefore, targeted therapy against linc-ITGB1 may be a novel strategy to treat HCC. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common cause of functional deterioration in older adults, and altered chondrogenesis is the most common pathophysiological process involved in the development of OA. MicroRNA-145 (miR-145) has been shown to regulate chondrocyte homeostasis. However, the function of miR-145 in OA remains to be elucidated. In the present study, the expression levels of miR-145 were examined in cartilage specimens from 25 patients with knee OA using reverse transcription-quantitative polymerase chain reaction analysis. The effects of miR-145 on the proliferation and fibrosis of the C-20/A4 and CH8 cell lines were also investigated using 3-(4,5-dimethylth-iazol-2-yl)-2,5-diphenyltetrazolium bromide and western blot assays in vitro. The results revealed that the expression of miR-145 was decreased in the OA cartilage tissues, compared with normal cartilage tissues. The overexpression of miR-145 by transfection of cells with miR-145 mimics significantly inhibited C-20/A4 and CH8 cell proliferation and fibrosis. Furthermore, tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) was identified as a direct target of miR-145 in chondrocytes, which was confirmed using a dual-luciferase reporter assay. The expression level of TNFRSF11B was markedly upregulated in the patients with OA, and the ectopic expression of miR-145 was capable of suppressing the expression of TNFRSF11B. In addition, the knock down of TNFRSF11B using specific small interfering RNA also inhibited the proliferation and fibrosis of C-20/A4 and CH8 cells in vitro. These data provide the first evidence, to the best of our knowledge, to suggest the critical function of miR-145 in regulating the expression of TNFRSF11B, which may have important implications on the regulation of chondrocyte proliferation and fibrosis in OA. [ABSTRACT FROM AUTHOR]

The high-mobility group box 1 (HMGB1) protein is a DNA-binding nuclear protein, which is overexpressed in leukemia cells. Cordycepin is characterized by strong antileukemic properties and is regarded as an effective natural compound for leukemia therapy. The aim of the present study was to investigate the impact of HMGB1 knockdown and cordycepin treatment on proliferation, apoptosis, reactive oxygen species (ROS) levels and adhesion of K562 human chronic myeloid leukemia cells. The Cell Counting kit-8 assay was used to determine the proliferation of K562 cells. The cell cycle and apoptosis of K562 cells was determined using flow cytometric analysis. In addition, a cell adhesion assay was performed. Western blotting was used to determine the protein expression of cyclooxygenase 2, Bax, receptor for advanced glycation end-products and Bcl-2. The data collected demonstrated that HMGB1 knockdown combined with cordycepin treatment had significant anti-proliferative and pro-apoptotic effects. In addition, it increased the ROS levels and reduced the adhesion of K562 cells. It was also identified that HMGB1 knockdown had synergistic effects with cordycepin, which aided in accelerating apoptosis, and inhibiting proliferation and adhesion in chronic myeloid leukemia cells. These results indicated that HMGB1 may be used as a potential therapeutic target, with cordycepin having potential as an auxiliary drug. Therefore, it is suggested that HMGB1 knockdown and corycepin treatement may present a promising therapeutic strategy for leukemia. [ABSTRACT FROM AUTHOR]

The function of microRNAs (miRNAs) in tumorigenesis has been extensively investigated. In the present study, the aim was to investigate the expression and role of miR-204 in B-cell lymphoma. The present study demonstrated that miR-204 is downregulated in B-cell lymphoma. Using in vitro studies, overexpression of miR-204 was shown to inhibit growth in Daudi and Raji B-cell lymphoma cell lines. Furthermore, miR-204 could bind the 3'-untranslated region of signal transducer activator of transcription 5 (STAT5), a transcription factor that promotes B-cell lymphoma oncogenesis. Re-introduction of STAT5 reversed the antiproliferative roles of miR-204, confirming the specific importance of STAT5 for miR-204 action in cell proliferation. The present study suggests a novel mechanism for dysregulated miRNAs in the progression of B-cell lymphoma. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the mechanism by which low-intensity intermittent negative pressure affects the differentiation and proliferation of human mesenchymal stem cells (MSCs). Alkaline phosphatase (ALP) activity, type I collagen and vascular endothelial growth factor (VEGF) were detected to analyze differentiation. MTT and flow cytometry were employed to measure proliferation and apoptosis. Western blot analysis was used to examine endoplasmic reticulum (ER) stress-associated factors. This study was divided into two groups, including a normal group (without any treatment) and vacuum group (treated with a vacuum). There was a significant decrease in the proliferation of cells in the vacuum group. The number of cells in S phase was reduced significantly, while the rate of apoptosis and the activity of ALP were markedly increased under vacuum conditions. Expression of collagen type I and VEGF was significantly increased, and the ratio of osteoprotegrin to osteoprotegrin ligand was decreased significantly in the vacuum group. ER stress-associated proteins, p-PRKR-like ER kinase, inositol-requiring enzyme 1 and cleaved activating transcription factor 6, as well as the downstream factors, were activated when treated with negative pressure. In conclusion, treatment with low-intensity and intermittent negative pressure may inhibit the proliferation of MSCs and trigger ER stress-associated cellular apoptosis, further enhancing osteogenesis activity and inducing differentiation to osteoblasts. [ABSTRACT FROM AUTHOR]