ADAM9 up-regulates N-cadherin via miR-218 suppression in lung adenocarcinoma cells.
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.
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
Yuh-Pyng
YP
Sher
Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
Li-Ju
LJ
Wang
Department of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan.
Li-Ling
LL
Chuang
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
Mong-Hsun
MH
Tsai
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Ting-Ting
TT
Kuo
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Cheng-Chung
CC
Huang
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
Eric Y
EY
Chuang
Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan; Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
Liang-Chuan
LC
Lai
D020413:3' Untranslated Regions; D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D015533:Transcriptional Activation
D020413:3' Untranslated Regions; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C547471:MIRN218 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D051722:ADAM Proteins; C098339:ADAM9 protein, human