title: MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptor.
abstract: MicroRNAs (miRNAs), which are noncoding RNAs that regulate gene expression, are involved in tumor metastasis. In this study, we describe the down-regulation and function of miR-139 in colorectal cancer (CRC) metastasis. MiR-139 was found underexpressed in 34 CRC tissues compared to their corresponding nontumor tissues. Decreased miR-139 in CRC tissue was associated with disease progression and metastasis. Re-expression of miR-139 did not inhibit CRC cell growth but suppresses CRC cell metastasis and invasion in vitro and in vivo. MiR-139 might suppress CRC cells invasion and metastasis by targeting type I insulin-like growth factor receptor (IGF-IR). We also found miR-139 directed migration inactivation of human CRC cells involves down-regulation of matrix metalloproteinase 2 (MMP-2). The IGF-IR/MEK/ERK signaling was inhibited by miR-139 overexpression and then resulted in MMP-2 promoter suppression. Taken together, our results provide evidence that miR-139 might function as a metastasis suppressor in CRC. Targeting miR-139 may provide a strategy for blocking CRC metastasis.
authors.affiliation: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Shen
authors.forename: Qiannan
authors.initials: Q
authors.lastname: Liang
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Daling
authors.initials: D
authors.lastname: Cui
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.forename: Peihao
authors.initials: P
authors.lastname: Yin
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Lu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D018390:Gene Targeting / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D017526:Receptor, IGF Type 1