title: MicroRNA-22 inhibits tumor growth and metastasis in gastric cancer by directly targeting MMP14 and Snail.
abstract: MicroRNAs (miRNAs) deregulation is frequent in human gastric cancers (GCs), but the role of specific miRNAs involved in this disease remains elusive. MiR-22 was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in GC are largely unclear. Here, we found that the expression of miR-22 was significantly reduced in clinical GC tissues compared with paired adjacent normal tissues, and was significantly correlated with a more aggressive phenotype of GC in patients, and miR-22 low expression correlated with poor overall survival. The introduction of miR-22 markedly suppressed GC cell growth, migration and invasion, and inhibition of miR-22 promoted GC cell proliferation, migration and invasion in vitro. We further demonstrated that miR-22 acted as tumor suppressors through targeting extracellular matrix (ECM) remodeling member matrix metalloproteinase 14 (MMP14) and epithelial-to-mesenchymal transition (EMT) inducer Snail in GC. Moreover, ectopic expression of MMP14 or Snail restored inhibitory effects of miR-22 on cell migration and invasion in GC cells, and a negative relationship between the miR-22 expression and MMP14 or Snail mRNA levels was observed in GC. Finally, overexpression of miR-22 suppressed tumor growth, peritoneal dissemination and pulmonary metastasis in vivo. Taken together, we identified that miR-22 is a potent tumor suppressor in GC. MiR-22 downregulation promotes GC invasion and metastasis by upregulating MMP14 and Snail, and then inducing ECM remodeling and EMT. These findings provide a better understanding of the development and progression of GC and may be an important implication for future therapy of the GC.
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Q-F
authors.initials: QF
authors.lastname: Zuo
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Cao
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: T
authors.initials: T
authors.lastname: Yu
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: L
authors.initials: L
authors.lastname: Gong
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: L-N
authors.initials: LN
authors.lastname: Wang
authors.affiliation: General Surgery and Center of Minimally Invasive Gastrointestinal Surgery, Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: B
authors.initials: B
authors.lastname: Xiao
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Q-M
authors.initials: QM
authors.lastname: Zou
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D064593:Heterografts; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14