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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]

Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC. [ABSTRACT FROM AUTHOR]

Slit homolog 2 (Slit2) is distributed in various tissues and participates in numerous cellular processes; however, the role of Slit2 in the regulation of angiogenesis remains controversial, since it has previously been reported to exert proangiogenic and antiangiogenic activities. The present study aimed to investigate the effects of Slit2 on vascular endothelial cell proliferation and migration in vitro, and to reveal the possible underlying signaling pathway. Aortic endothelial cells were isolated from Sprague Dawley rats and cultured. Cell proliferation assay, cell migration assay, immunocytochemistry and small interfering RNA transfection were subsequently performed. The results demonstrated that exogenous Slit2 administration markedly suppressed TNF-α-induced endothelial cell proliferation and migration in vitro. In addition, TNF-α application upregulated the protein expression levels of vascular endothelial growth factor (VEGF) and Notch in RAECs, whereas Slit2 administration downregulated VEGF and Notch expression in RAECs cultured in TNF-α conditioned medium. Further studies indicated that knockdown of VEGF suppressed the effects of TNF-α on the induction of RAEC proliferation and migration. VEGF knockdown-induced inhibition of RAEC proliferation and migration in TNF-α conditioned medium was also achieved without Slit2 administration. Furthermore, VEGF knockdown markedly decreased Notch1 and Notch2 expression. These results indicated that Slit2 suppresses TNF-α-induced vascular endothelial cell proliferation and migration in vitro by inhibiting the VEGF-Notch signaling pathway. Therefore, Slit2 may inhibit the proliferation and migration of endothelial cells during vascular development. [ABSTRACT FROM AUTHOR]

The prostaglandin E2 (PGE2) E prostanoid (EP)1 receptor shown to be associated with lung cancer cell invasion. However, the mechanism of EP1 receptor-mediated cell migration remains to be elucidated. β1 integrin is an essential regulator of the tumorigenic properties of non-small-cell lung carcinoma (NSCLC) cells. To date, little is known regarding the association between the EP1 receptor and β1 integrin expression. The present study investigated the effect of EP1 receptor activation on β1 integrin expression and cell migration in NSCLC cells. A total of 34 patients with clinical diagnosis of NSCLC and 10 patients with benign disease were recruited for the present study. The expression levels of the EP1 receptor and β1 integrin expression were studied in resected lung tissue using immunohistochemistry. A statistical analysis was performed using Stata sel2.0 software. The effects of PGE2, EP1 agonist 17-phenyl trinor-PGE2 (17-PT-PGE2) and the nuclear factor κ-B (NF-κB) inhibitor on β1 integrin expression were investigated on A549 cells. The expression of (31 integrin and the phosphorylation of NF-κB-p65 Ser536 was investigated by western blot analysis. Cell migration was assessed by a transwell assay. The results demonstrated that (31 integrin and EP1 receptor expression exhibited a positive correlation of evident significance in the 44 samples. The in vitro migration assay revealed that cell migration was increased by 30% when the cells were treated with 5 μM 17-PT-PGE2 and that the pre-treatment of β1 integrin monoclonal antibody inhibited 17-PT-PGE2-mediated cell migration completely. PGE2 and 17-PT-PGE2 treatment increased β1 integrin expression. RNA interference against the EP1 receptor blocked the PGE2-mediated β1 integrin expression in A549 cells. Treatment with 17-PT-PGE2 induced NF-κB activation, and the selective NF-kB inhibitor pyrrolidin-edithiocarbamate inhibited 17-PT-PGE2-mediated β1 integrin expression. In conclusion, the present study indicated that the PGE2 EP1 receptor regulates β1 integrin expression and cell migration in NSCLC cells by activating the NF-kB signaling pathway. Targeting the PGE2/EP1/β1 integrin signaling pathway may aid in the development of new therapeutic strategies for the prevention and treatment of this type of cancer. [ABSTRACT FROM AUTHOR]