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Protein Jumonji (JARID2), a member of the family of JmjC domain-containing proteins, has been reported to serve an important role in tumor growth and metastasis. However, the expression pattern and role of JARID2 in ovarian cancer remains unclear. Therefore, in the present study, the role of JARID2 in ovarian cancer was investigated, as well as the underlying mechanisms. The results of the present study demonstrated that the expression of JARID2 is upregulated in human ovarian cancer cell lines. Furthermore, downregulation of JARID2 significantly suppressed proliferation, migration, invasion and epithelial‑mesenchymal transition in human ovarian cancer cells. Mechanistically, downregulation of JARID2 decreased the protein expression levels of phosphorylated phosphoinositide 3‑kinase (PI3K) and protein kinase B (Akt) in ovarian cancer cells. In conclusion the observations suggested that knockdown of JARID2 inhibited proliferation, migration and invasion in vitro through the inactivation of the PI3K/Akt signaling pathway. Therefore, JARID2 may represent a potential therapeutic target for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) metastasis may result from epithelial-to-mesenchymal transition and mesenchymal stem cells that contribute to the development of the primary tumor. In this study, it was demonstrated that microRNA-21 (miR-21) acts as an oncogenic driver of ccRCC. ccRCC spheres were isolated and it was shown that they exhibited cancer stem cell-like properties, including the formation of self-renewing spheres. Spheres showed increased expression of stem cell-related transcription factors and epithelial-mesenchymal transition (EMT) markers. In addition, secondary sphere formation capacity was assessed after miR-21 transfection. miR-21 accelerated the formation of ccRCC spheres, which shared molecular characteristics with the spontaneous ccRCC spheres. It was demonstrated that miR-21 overexpression facilitates ccRCC sphere formation. Thus, a single miRNA may have an impact on the formation of highly tumorigenic cancer spheres in kidney cancer. [ABSTRACT FROM AUTHOR]

Accumulating evidence has suggested that homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS). Hcy can promote vascular smooth muscle cell (VSMC) proliferation, which is pivotal in the pathogenesis and progression of AS. The aim of the present study was to investigate the epigenetic regulatory mechanism of microRNA (miR).143.mediated VSMCs proliferation induced by Hcy. The results of a 3.(4,5.dimethylthiazol.2.yl).2,5.diphe.nyltetrazolium bromide assay revealed that VSMC proliferation was increased by 1.39.fold following treatment with 100 mM Hcy, compared with the control group. The levels of miR.143 were markedly downregulated in the Hcy group, compared with the control group, as determined using reverse transcription.quantitative polymerase chain reaction analysis. In addition, the level of miR.143 methylation was increased markedly in the VSMCs treated with Hcy, compared with the control, and was reduced following transfection with DNA methyltransferase (DNMT)3a small interfering RNA, determined using methylation.specific.PCR. The activities of DNMT3a luciferase were also altered accordingly in VSMCs transfected with pre-miR-143 and miR-143 inhibitor, respectively. In addition, the expression of miR-143 was observed to be inversely correlated with the mRNA and protein expression of DNMT3 in the VSMCs. Taken together, these findings suggest that DNMT3a is a direct target of miR-143, and that the upregulation of DNMT3 is responsible for the hypermethylation of miR-143 in Hcy-induced VSMC proliferation. [ABSTRACT FROM AUTHOR]

The current study aimed to verify an miRNA signature in endothelial cells undergoing mechanical stretch stimulation. In the present study, microarray profiling was conducted in order to identify the differential expression of miRNAs in endothelial cells undergoing mechanical stimulation, compared with unstimulated endothelial cells. The microarray data was then validated by reverse transcription-quantitative polymerase chain reaction. Genes and signaling pathways regulated by the miRNAs were investigated in silico using Gene Ontology and the Kyoto Encyclopedia of Genes or Genomes, which are ontological and network-mapping algorithms. The microarray data collected demonstrated that 38 miRNAs exhibited significant differential expression in endothelial cells with mechanical stretch stimulation. Of these, 20 were upregulated and 18 were downregulated. The results from the in silico analysis indicated that the miRNAs identified were participants in mechanical stretch-induced endothelial dysfunction. During the initial stage of vein graft failure, which is induced by endothelial dysfunction, a unique miRNA signature was identified. The identified miRNAs are suggested to be involved in the pathological processes of traumatic injury. [ABSTRACT FROM AUTHOR]

A number of microRNAs (miRs) have been shown to participate in the regulation of vascular smooth muscle cell (VSMC) proliferation, a key step in the formation of atherosclerotic plaque, by targeting certain genes. The aim of the present study was to investigate the roles of miR-146a and miR-21 in VSMC growth and to study the underlying mechanisms. The expression levels of four previously reported, differentially expressed microRNAs in atherosclerotic plaque (miR-146a/b, miR-21, miR-34a and miR-210) were measured in two groups: An atherosclerotic plaque group (n=10) and a normal control group (n=10). Polymerase chain reaction (PCR) analysis revealed that the relative expression levels of miR-146a and miR-21 in atherosclerotic plaque samples were significantly upregulated to ~260 and 250%, respectively, compared with those in normal controls. Notch2 and Jag1 were confirmed to be target genes of miR-146a and miR-21 through the use of a luciferase assay, PCR and western blot analysis. Additionally, VSMCs transfected with miR-146a expressed significantly lower levels of Notch2 protein and presented an accelerated cell proliferation, which could be attributed to a reduction in the levels of cell cycle arrest. Cotransfection of miR-146a and miR-21 further promoted cell cycle progression in addition to VSMC proliferation. In conclusion, the present study revealed that miR-146a and miR-21 were significantly upregulated in atherosclerotic plaque, and cooperated to accelerate VSMC growth and cell cycle progression by targeting Notch2 and Jag1. [ABSTRACT FROM AUTHOR]

It is well established that homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS), which is characterized by vascular smooth muscle cell (VSMC) proliferation. However, the molecular mechanism underlying AS in VSMCs is yet to be elucidated. The aim of this study was to investigate the potential involvement of aberrant DNA methylation of the platelet-derived growth factor (PDGF) gene in Hcy-mediated VSMC proliferation and its underlying mechanism. Cultured human VSMCs were treated with varying concentrations of Hcy. VSMC proliferation, PDGF mRNA and protein expression and PDGF promoter demethylation showed a dose-dependent increase with Hcy concentration, suggesting an association among them. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase, indicating that VSMC proliferation was increased under Hcy treatment. Furthermore, S-adenosylhomocysteine (SAH) levels were observed to increase and those of S-adenosylmethionine (SAM) were observed to decrease. The consequent decrease in the ratio of SAM/SAH may partially explain the hypomethylation of PDGF with Hcy treatment. Folate treatment exhibited an antagonistic effect against Hcy-induced VSMC proliferation, aberrant PDGF methylation and PDGF expression. These data suggest that Hcy may stimulate VSMC proliferation through the PDGF signaling pathway by affecting the epigenetic regulation of PDGF through the demethylation of its promoter region. These findings may provide novel insight into the molecular association between aberrant PDGF gene demethylation and the proliferation of VSMCs in Hcy-associated AS. [ABSTRACT FROM AUTHOR]