title: MicroRNA-409-3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression.
abstract: Colorectal cancer (CRC) is one of the most common cancers worldwide and its metastasis accounts for the majority of deaths. However, the molecular mechanisms underlying CRC progression are not well characterized. In this study, we identified miR-409-3p as a tumor suppressor of CRC. MiR-409-3p expression was significantly downregulated in CRC tissue compared to adjacent non-tumor tissue, and reduced miR-409-3p expression was correlated with CRC metastasis. In vitro and in vivo studies revealed that miR-409-3p negatively regulated CRC metastatic capacities, including suppressing cancer cell migration, invasion and metastasis. To explore the mechanism of action of miR-409-3p, we adopted a pathway and pathophysiological event-based target screening and validation approach, and found nine known metastasis-related genes as potential targets. The 3'-UTR binding assays between the candidates and miR-409-3p suggested that only GAB1, NR4A2 and LMO4 were directly regulated by the miRNA. However, endogenous expression analysis revealed that only GAB1 was modulated by miR-409-3p in CRC cells at both the mRNA and protein levels. Furthermore, we provided evidence to conclude that GAB1 was partially responsible for miR-409-3p-mediated metastasis. Taken together, our data demonstrate that miR-409-3p is a metastatic suppressor, and post-transcriptional inhibition of the oncoprotein GAB1 is one of the mechanisms of action of this miRNA. Our finding suggests miR-409-3p might be a novel target for CRC metastasis treatment.
authors.affiliation: Institute of Environmental Health, Zhejiang University School of Public Health, Hangzhou, China.|Research Center of Molecular Medicine, Zhejiang University School of Medicine, Hangzhou, China.|Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Rongpan
authors.initials: R
authors.lastname: Bai
authors.affiliation: Institute of Environmental Health, Zhejiang University School of Public Health, Hangzhou, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Weng
authors.affiliation: Institute of Environmental Health, Zhejiang University School of Public Health, Hangzhou, China.|Research Center of Molecular Medicine, Zhejiang University School of Medicine, Hangzhou, China.|Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Dong
authors.affiliation: Institute of Environmental Health, Zhejiang University School of Public Health, Hangzhou, China.|Research Center of Molecular Medicine, Zhejiang University School of Medicine, Hangzhou, China.|Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Environmental Health, Zhejiang University School of Public Health, Hangzhou, China.|Research Center of Molecular Medicine, Zhejiang University School of Medicine, Hangzhou, China.|Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Chen
authors.affiliation: Institute of Environmental Health, Zhejiang University School of Public Health, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.|Research Center of Molecular Medicine, Zhejiang University School of Medicine, Hangzhou, China.|Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; C572367:MIRN409 microRNA, human; D035683:MicroRNAs
keywords: GAB1; colorectal cancer; microRNA-409-3p; tumor metastasis