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Macrophage and Cancer Cell Crosstalk Regulated MicroRNA 147b Plays a Crucial Role in Lung Cancer Progression
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A2684 - Macrophage and Cancer Cell Crosstalk Regulated MicroRNA 147b Plays a Crucial Role in Lung Cancer Progression
Author Block: K. Turkowski1, T. Haselbauer1, S. Kaduthanam2, H. Sültmann2, F. Grimminger3, W. Seeger3, R. Savai1; 1Molecular Mechanisms in Lung Cancer, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, 2Cancer Genome Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, 3Justus-Liebig-Univ Giessen, Giessen, Germany.
In the lung cancer microenvironment, macrophages are a major component and one of the key effector cells regarding lung cancer development and progression. Cancer cells regulate several miRNAs in immune cells to limit their antitumor response and reprogram them to promote tumorigenesis. The molecular cues that control macrophage/ tumor crosstalk in the lung are only partially understood.
Using a microRNA microarray- based approach we have found that miR-147b is highly induced in cancer cells co-cultured with macrophages. We could confirm the upregulation of miR-147b data in different human lung cancer cell lines co-cultured with macrophages as well as human lung cancer tissue. In vivo we could show that after macrophage depletion using the MaFIA-mouse model the expression of miR-147b is significantly downregulated, indicating a macrophage - dependent expression. Overexpression of miR-147b in A549 adenocarcinoma cells reveals a significant increase in proliferation, colony formation, and migration and resulted in epithelial to mesenchymal transition in vitro. To identify miR-147 target genes especially related to cancer pathways we used the NanoString approach. We found that most of the genes affected by overexpression of miR-147b are related to the MAPK, RAS, and PI3K pathways. To identify target genes regulated by miR-147b, we searched the database microRNA.org. Further, we confirmed selected target genes (FGF14, DTX4 and DUSP8) by luciferase gene reporter assays in miR-147b overexpressing cells.
We conclude that interference of this microRNA and further investigations on miR-147b target genes and related pathways will provide new opportunities for lung cancer targeted therapies.
Author Block: K. Turkowski1, T. Haselbauer1, S. Kaduthanam2, H. Sültmann2, F. Grimminger3, W. Seeger3, R. Savai1; 1Molecular Mechanisms in Lung Cancer, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, 2Cancer Genome Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany, 3Justus-Liebig-Univ Giessen, Giessen, Germany.
In the lung cancer microenvironment, macrophages are a major component and one of the key effector cells regarding lung cancer development and progression. Cancer cells regulate several miRNAs in immune cells to limit their antitumor response and reprogram them to promote tumorigenesis. The molecular cues that control macrophage/ tumor crosstalk in the lung are only partially understood.
Using a microRNA microarray- based approach we have found that miR-147b is highly induced in cancer cells co-cultured with macrophages. We could confirm the upregulation of miR-147b data in different human lung cancer cell lines co-cultured with macrophages as well as human lung cancer tissue. In vivo we could show that after macrophage depletion using the MaFIA-mouse model the expression of miR-147b is significantly downregulated, indicating a macrophage - dependent expression. Overexpression of miR-147b in A549 adenocarcinoma cells reveals a significant increase in proliferation, colony formation, and migration and resulted in epithelial to mesenchymal transition in vitro. To identify miR-147 target genes especially related to cancer pathways we used the NanoString approach. We found that most of the genes affected by overexpression of miR-147b are related to the MAPK, RAS, and PI3K pathways. To identify target genes regulated by miR-147b, we searched the database microRNA.org. Further, we confirmed selected target genes (FGF14, DTX4 and DUSP8) by luciferase gene reporter assays in miR-147b overexpressing cells.
We conclude that interference of this microRNA and further investigations on miR-147b target genes and related pathways will provide new opportunities for lung cancer targeted therapies.
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