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MicroRNAs (miRNAs) represent a class of small non-coding RNAs regulating gene expression by inducing the degradation of RNA or interfering with translation. Aberrant miRNA expression has been described in several types of cancer in humans. In the present study, it was demonstrated that miR-145 is downregulated in pancreatic cancer tissues and the Panc-1 cell line. Restoration of miR-145 inhibited cell proliferation, invasion and migration in Panc-1 cells. Neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) has been identified as a novel potential miR-145 target using bioinformatics. Using luciferase reporter constructs, it was observed that the NEDD9 3'-untranslated region is the location of the direct binding site for miR-145. Additionally, it was identified that miR-145 is inversely correlated with NEDD9 expression in pancreatic cancer tissues and that restoration of miR-145 in Panc-1 cells reduced NEDD9 mRNA and protein expression accompanied by inhibition of cell proliferation, invasion and migration. In conclusion, these findings indicate that miR-145 may be an effective target for pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) comprises the 3rd cause of cancer-related death worldwide. Increased expression of neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is commonly observed in GC, however, its underlying molecular mechanism in GC remains unknown. The potential interaction between miR-4735-3p and NEDD9 was predicted by TargetScan 7.1. Expression profiles of miR-4735-3p and NEDD9 were examined between GC tissues and normal tissues by reverse transcription-quantitative (RT-q) PCR. The relationship between miR-4735-3p and NEDD9 was validated by RT-qPCR, western blotting, dual luciferase reporter assay and RNA immunoprecipitation assay. Biological relationship between miR-4735-3p and NEDD9 was evidenced by the cell invasion and cell migration assays. NEDD9 level was negatively associated with miR-4735-3p level in GC tissues. miR-4735-3p suppressed NEDD9 levels in GC cells. NEDD9 was revealed to be a target gene of miR-4735-3p. miR-4735-3p overexpression suppressed cell migration and invasion of GC cells, which were antagonized by overexpression of NEDD9. Moreover, miR-4735-3p mimic decreased the levels of matrix metalloproteinases 2/9, increased the level of E-cadherin, which were reversed by overexpression of NEDD9. Collectively, the present study provided a potential mechanism for the tumor suppressor role of miR-4735-3p in GC by targeting NEDD9. [ABSTRACT FROM AUTHOR]

Abstract: The NEDD9 rs760678 polymorphism has been extensively investigated for association to Alzheimer''s disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NEDD9 rs760678 polymorphism and AD risk by using meta-analysis. Systematic searches of electronic databases Pubmed and Embase, as well as hand searching of the references of identified articles were performed. Statistical analyses were performed using software Revman 4.2 and STATA 11.0. A total of 4436 cases and 4420 controls in 11 case–control studies were included. The results indicated that the homozygote GG had a 13% decreased risk of AD, when compared with the C allele carriers (CC+CG) (OR=0.87, 95%CI=0.77–0.99, P =0.04 for GG vs. CG+CC). In the subgroup analysis by ethnicity, significant decreased risk was associated with homozygote GG or G allele carriers in Caucasians (OR=0.84, 95%CI=0.74–0.96, P =0.008 for GG vs. CG+CC; OR=0.79, 95%CI=0.69–0.91, P =0.001 for GG vs. CC; OR=0.90, 95%CI=0.84–0.96, P =0.002 for G vs. C), but not in Asians. This meta-analysis suggests that the GG genotype of NEDD9 rs760678 polymorphism would be a protective factor for AD in Caucasians but not in Asians. To further evaluate the effect of gene–gene and gene–environmental interactions between NEDD9 rs760678 polymorphism and the risk of AD, more studies with larger number of subjects are required. [Copyright &y& Elsevier]

Overexpression of neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is a prognostic marker of many cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of NEDD9 are unclear. We found that upregulation of NEDD9 promoted migration, invasion and cell-to-extracellular matrix adhesion of HCC cells. NEDD9 also induced the epithelial-mesenchymal transition (EMT) and expression of matrix metalloprotein 2 (MMP2). Increased aldehyde dehydrogenase (ALDH) activity and CD133-positive cells were observed in HCC cells with high expression of NEDD9, corresponding to greater sphere formation in cancer stem cells (CSCs). NEDD9 deregulated Smad7 expression to inhibit Smad signaling and binding to the FAK-Src-Crk complex. We propose that this is the mechanism by which NEDD9 induced CSC properties.