1. Inhibition of RAC1-GEF DOCK3 by miR-512-3p contributes to suppression of metastasis in non-small cell lung cancer.
- Author
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Zhu X, Gao G, Chu K, Yang X, Ren S, Li Y, Wu H, Huang Y, and Zhou C
- Subjects
- Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Cell Line, Tumor, Cell Movement drug effects, Cell Movement genetics, Cell Proliferation, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Down-Regulation, Guanine Nucleotide Exchange Factors genetics, Guanine Nucleotide Exchange Factors metabolism, Humans, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Lung Neoplasms pathology, MicroRNAs biosynthesis, Microarray Analysis, Neoplasm Invasiveness, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Transcription Factors genetics, Transcription Factors metabolism, Transfection, Tretinoin pharmacology, rac1 GTP-Binding Protein genetics, rac1 GTP-Binding Protein metabolism, Carcinoma, Non-Small-Cell Lung genetics, DNA-Binding Proteins antagonists & inhibitors, Guanine Nucleotide Exchange Factors antagonists & inhibitors, Lung Neoplasms genetics, MicroRNAs genetics, Nerve Tissue Proteins antagonists & inhibitors, Transcription Factors antagonists & inhibitors, rac1 GTP-Binding Protein antagonists & inhibitors
- Abstract
MicroRNAs are a class of small non-coding RNAs regulating gene expression. In this study, we demonstrated that retinoic acid (RA) treatment increases the expression of miR-512-3p. Overexpression of miR-512-3p inhibited cell adhesion, migration, and invasion in non-small cell lung cancer (NSCLC) cell lines A549 and H1299. miR-512-3p inhibitor partially reversed these effects in H1299 cells stably expressing miR-512. We identified DOCK3, a RAC1-GEF (guanine nucleotide exchange factor), as a target gene of miR-512-3p. Overexpression of miR-512-3p led to the decrease of DOCK3 protein but not its mRNA. Knockdown of DOCK3 resulted in similar effects on adhesion, migration, and invasion as observed of miR-512-3p overexpression. Active RAC1 pull-down assay indicated that overexpression of miR-512-3p could decrease the activity of RAC1 with a higher efficiency than that of DOCK3 knockdown. Furthermore, expression of miR-512-3p was suppressed in most NSCLC patient tumor samples compared to its paired normal controls, suggesting that miR-512-3p might play a crucial role in lung cancer development. In conclusion, our results supported that miR-512-3p could inhibit tumor cell adhesion, migration, and invasion by regulating the RAC1 activity via DOCK3 in NSCLC A549 and H1299 cell lines., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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