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ADAM9 Up-regulates N-Cadherin via MiR-218 Suppression in Lung Adenocarcinoma Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52051 | GEO | 2016/01/01

SECONDARY ACCESSION(S): PRJNA226585

REPOSITORIES: GEO

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ADAM9 up-regulates N-cadherin via miR-218 suppression in lung adenocarcinoma cells.

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ADAM9 Up-regulates N-Cadherin via MiR-218 Suppression in Lung Adenocarcinoma Cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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ADAM9 Up-regulates N-Cadherin via MiR-218 Suppression in Lung Adenocarcinoma Cells

Project description:Identification of miRNAs that differentially expressed in brain metastatic cells and were predicted to target CDH2. To investigate which miRNAs could regulate CDH2 expression in brain-metastatic lung cancer cells, we examined the miRNA expression profiles in brain-metastatic lung cancer cells and their parental cells using Illumina miRNA microarray. By comparing the endogenous expression of all miRNAs, 146 miRNAs were selected by 2-fold changes in brain-metastatic lung cancer cells. Furthermore, we used several algorithms in miRSystem to predict which miRNA whose target gene was CDH2. There were 44 miRNAs that were predicted to target CDH2. In total, we identified nine miRNAs whose target gene was CDH2 and whose expression was significantly different between the highly metastatic cells and their parental cells (Fig. 2A). Among these miRNAs, four miRNAs were found to be down-regulated and five miRNAs were up-regulated in brain-metastatic lung cancer cells (Fig. 2B).

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ADAM9 Up-regulates N-Cadherin via MiR-218 Suppression in Lung Adenocarcinoma Cells [mRNA]

Project description:Lung cancer is the leading cause of cancer death worldwide. Brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker in epithelial-mesenchymal transition) and ADAM9 (a member of type I transmembrane proteins) have been reported relating to lung cancer brain metastasis, however, it is still not clear whether any interaction between them to mediate lung cancer brain metastasis. Since microRNAs were discovered to regulate many biological functions and disease processes (e.g., cancer) by down-regulating their target genes, microRNA microarrays were used to identify ADAM9 regulated miRNAs that target CDH2 in aggressive lung cancer cells. Luciferase assays and immunoblotting proved that CDH2 was a target gene of miR-218. The expression of miR-218 was generated from pri-mir-218-1, located in SLIT2, in low invasive lung adenocarcinoma while it was inhibited in aggressive lung adenocarcinoma. Down-regulation of ADAM9 could up-regulate SLIT2 and miR-218, thus down-regulate CDH2 expression. This study elucidated the mechanism of ADAM9 activating CDH2 may be due to release the inhibition of miR-218 on CDH2 in lung adenocarcinoma. For each of the cell lines bm#2, bm#7, and F4, one microarray was analyzed.

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