ADAM9 Up-regulates N-Cadherin via MiR-218 Suppression in Lung Adenocarcinoma Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52051 | GEO | 2016/01/01
SECONDARY ACCESSION(S): PRJNA226585
REPOSITORIES: GEO
Similar Datasets
Project description: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.
| S-EPMC3976390 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-03 | E-GEOD-52051 | biostudies-arrayexpress
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).
2016-10-11 | GSE51666 | GEO
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.
2016-07-03 | E-GEOD-52050 | biostudies-arrayexpress
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.
2016-07-03 | E-GEOD-51833 | biostudies-arrayexpress
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.
2016-01-01 | GSE52050 | GEO
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.
2016-01-01 | GSE51833 | GEO
Project description:Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3'-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis.
| S-EPMC4639752 | biostudies-other
Project description:BackgroundLung adenocarcinoma (LUAD) is currently the leading cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) play key roles in tumor occurrence and development as crucial cancer regulators. The present study aimed to explore the molecular mechanism and regulatory network of Linc00511 in LUAD and to identify new potential therapeutic targets for LUAD.MethodsReal-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine the relative Linc00511 levels in LUAD tissues and cells. The proliferation, apoptosis, migration, and invasion abilities of LUAD cells were assessed by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, flow cytometry, and a Transwell assay. Changes in hsa_miR-126-5p, hsa_miR-218-5p, and COL1A1 expression were analyzed using western blotting and RT-qPCR. Targeted binding between miR-126-5p/miR-218-5p and Linc00511 or COL1A1 was verified with a luciferase reporter system and confirmed by an RNA pulldown assay. The participation of the PI3K/AKT signaling pathway was confirmed via western blotting. Xenograft animal experiments were performed to detect the impact of Linc00511 on LUAD tumor growth in vivo.ResultsIn the present work, we observed that Linc00511 was upregulated in LUAD tissues and cells. Loss/gain-of-function experiments indicated that knockdown of Linc00511 significantly inhibited LUAD cell proliferation, migration and invasion and promoted LUAD cell apoptosis, whereas overexpression of Linc00511 showed the opposite effects. In addition, we determined that Linc00511 promoted COL1A1-mediated cell proliferation and cell motility by sponging miR-126-5p and miR-218-5p. Moreover, Linc00511 activated the PI3K/AKT signaling pathway through upregulation of COL1A1. Finally, silencing of Linc00511 inhibited LUAD tumor growth in vivo.ConclusionsLinc00511 acts as a competing endogenous RNA to regulate COL1A1 by targeting miR-126-5p and miR-218-5p, thereby promoting the proliferation and invasion of LUAD cells.
| S-EPMC9287882 | biostudies-literature
Project description:Circular RNA (circRNA) is considered an important regulator of cancer. Circ_0001998 is a newly discovered circRNA and its role in lung adenocarcinoma (LUAD) remains obscure and requires further study. The expression levels of circ_0001998 and miR-145 in LUAD were predicted by bioinformatics analysis and then verified by qRT-PCR in the LUAD cell lines. CCK-8, clone formation, EdU assay, and flow cytometry were applied to determine the effects of silencing circ_0001998 on the viability, proliferation, and apoptosis of LUAD cells. The target relationship between circ_0001998 and miR-145 was predicted by bioinformatics analysis and verified by a luciferase activity experiment. The effect of circ_0001998/miR-145 axis on the viability, proliferation, and apoptosis of LUAD cells was verified by the rescue experiment. Circ_0001998 was upregulated in LUAD, and silencing circ_0001998 suppressed viability, proliferation, and invasion of LUAD cells. The target gene of circ_0001998, miR-145, was downregulated in LUAD, and the low expression of miR-145 indicated a poor prognosis. The effect of silencing circ_0001998 on the biological function of LUAD cells was reversed by the miR-145 inhibitor. Circ_0001998 regulates the proliferation, invasion, and apoptosis of LUAD via sponging miR-145.
| S-EPMC9117027 | biostudies-literature