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- Title
ADAM9 Up-Regulates N-Cadherin via miR-218 Suppression in Lung Adenocarcinoma Cells.
- Authors
Sher, Yuh-Pyng; Wang, Li-Ju; Chuang, Li-Ling; Tsai, Mong-Hsun; Kuo, Ting-Ting; Huang, Cheng-Chung; Chuang, Eric Y.; Lai, Liang-Chuan
- 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.
- Subjects
LUNG cancer; CADHERINS; MICRORNA; PHYSIOLOGICAL control systems; BRAIN metastasis; CANCER-related mortality; ETIOLOGY of cancer
- Publication
PLoS ONE, 2014, Vol 9, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0094065