ADAM9 up-regulates N-cadherin via miR-218 suppression in lung adenocarcinoma cells
Journal
PLoS ONE
Journal Volume
9
Journal Issue
4
Pages
e94065
Date Issued
2014
Author(s)
Abstract
Lung cancer is the leading cause of cancer death worldwide, and brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker of the epithelial-mesenchymal transition) and ADAM9 (a type I transmembrane protein) are related to lung cancer brain metastasis; however, it is unclear how they interact to mediate this metastasis. Because microRNAs 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 western blot analysis showed that CDH2 is a target gene of miR-218. MiR-218 was generated from pri-mir-218-1, which is located in SLIT2, in non-invasive lung adenocarcinoma cells, whereas its expression was inhibited in aggressive lung adenocarcinoma. The down-regulation of ADAM9 up-regulated SLIT2 and miR-218, thus down-regulating CDH2 expression. This study revealed that ADAM9 activates CDH2 through the release of miR-218 inhibition on CDH2 in lung adenocarcinoma. ? 2014 Sher et al.
SDGs
Other Subjects
ADAM9 protein; membrane protein; microRNA; microRNA 218; nerve cell adhesion molecule; unclassified drug; 3' untranslated region; ADAM protein; ADAM9 protein, human; cadherin; CDH2 protein, human; leukocyte antigen; membrane protein; microRNA; MIRN218 microRNA, human; ADAM9 gene; article; brain metastasis; carcinoma cell; CDH2 gene; controlled study; down regulation; gene; gene control; gene repression; gene targeting; human; human cell; luciferase assay; lung adenocarcinoma; microarray analysis; morbidity; mortality; nucleotide sequence; upregulation; Western blotting; 3' untranslated region; adenocarcinoma; binding site; cell motion; chemistry; cluster analysis; gene expression profiling; gene expression regulation; genetics; lung tumor; metabolism; nucleotide sequence; pathology; RNA interference; transcription initiation; tumor cell line; 3' Untranslated Regions; ADAM Proteins; Adenocarcinoma; Antigens, CD; Base Sequence; Binding Sites; Cadherins; Cell Line, Tumor; Cell Movement; Cluster Analysis; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Membrane Proteins; MicroRNAs; RNA Interference; Transcriptional Activation
Publisher
Public Library of Science
Type
journal article