title: Inhibition of RAC1-GEF DOCK3 by miR-512-3p contributes to suppression of metastasis in non-small cell lung cancer.
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.
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, PR China.
authors: Xingli
authors: X
authors: Zhu
authors: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Cancer Institute, Shanghai 200433, PR China.
authors: Guanghui
authors: G
authors: Gao
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, PR China.
authors: Kaili
authors: K
authors: Chu
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, PR China.
authors: Xiufang
authors: X
authors: Yang
authors: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Cancer Institute, Shanghai 200433, PR China.
authors: Shengxiang
authors: S
authors: Ren
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, PR China.
authors: Yao
authors: Y
authors: Li
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, PR China.
authors: Hai
authors: H
authors: Wu
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, PR China. Electronic address: huangyan@fudan.edu.cn.
authors: Yan
authors: Y
authors: Huang
authors: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Cancer Institute, Shanghai 200433, PR China.
authors: Caicun
authors: C
authors: Zhou
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C485840:DOCK3 protein, human; D020662:Guanine Nucleotide Exchange Factors; C000595430:MIRN512 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C107953:RAC1 protein, human; C480633:SLC2A4RG protein, human; D014157:Transcription Factors; D014212:Tretinoin; D020830:rac1 GTP-Binding Protein
keywords: Adhesion; DOCK3; Invasion; Migration; miR-512-3p