ADAM9 Up-Regulates N-Cadherin via miR-218 Suppression in Lung Adenocarcinoma CellsReportar como inadecuado

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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.

Autor: Yuh-Pyng Sher, Li-Ju Wang, Li-Ling Chuang, Mong-Hsun Tsai, Ting-Ting Kuo, Cheng-Chung Huang, Eric Y. Chuang, Liang-Chuan Lai



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