title: Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma.
abstract: MicroRNAs (miRNAs) are endogenous non-coding RNAs that are known to be involved in the pathogenesis of tumors. Gastric carcinoma (GC) is a common malignancy worldwide. The aim of this study was the identification of the expression signature and functional roles of aberrant miRNAs in GC. Initial screening established a profile of aberrantly expressed miRNAs in tumors. miR-370 was confirmed to be overexpressed in GC tissues. Higher expression of miR-370 in GC tissues was associated with more advanced nodal metastasis and a higher clinical stage compared with controls. In addition, significantly higher level of miR-370 was noted in the plasma of GC patients compared with controls. Patients having more invasive or advanced tumors also exhibited a higher plasma level of miR-370. In vitro assays indicated that exogenous miR-370 expression enhanced the oncogenic potential of GC cells. The AGS-GFPM2 cells with exogenous miR-370 expression also exhibited enhanced abdominal metastatic dissemination in nude mice. Reporter assays confirmed that miR-370 targeted predicted sites in 3'UTR of transforming growth factor-β receptor II (TGFβ-RII) gene. The exogenous miR-370 expression decreased TGFβ-RII expression and the phosphorylation of Smad3 elicited by TGFβ1. The TGFβ1-mediated repression in cell migration was reverted by exogenous miR-370 expression. A reverse correlation between miR-370 and TGFβ-RII expression was noted in GC tissues. This study concludes that miR-370 is a miRNA that is associated with GC progression by downregulating TGFβ-RII. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in GC.
authors.affiliation: Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. sslo@ymuh.ym.edu.tw
authors.forename: S-S
authors.initials: SS
authors.lastname: Lo
authors.forename: P-S
authors.initials: PS
authors.lastname: Hung
authors.forename: J-H
authors.initials: JH
authors.lastname: Chen
authors.forename: H-F
authors.initials: HF
authors.lastname: Tu
authors.forename: W-L
authors.initials: WL
authors.lastname: Fang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chen
authors.forename: W-T
authors.initials: WT
authors.lastname: Chen
authors.forename: N-R
authors.initials: NR
authors.lastname: Gong
authors.forename: C-W
authors.initials: CW
authors.lastname: Wu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C526503:MIRN370 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II