title: MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers.
abstract: Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3'-untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.
authors.affiliation: Department of Gastric Cancer and Soft Tissue Sarcomas, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.forename: L
authors.initials: L
authors.lastname: Liang
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Zha
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Jia
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Long
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: X
authors.initials: X
authors.lastname: Cao
authors.forename: C
authors.initials: C
authors.lastname: Du
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: X
authors.initials: X
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; C572367:MIRN409 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C071776:radixin