title: MicroRNA let-7f inhibits tumor invasion and metastasis by targeting MYH9 in human gastric cancer.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers.
  
  
  RESULTS
  Real-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3'UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels.
  
  
  CONCLUSIONS
  Our study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis.
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital of Digestive Diseases, Xi'an, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Liang
authors.forename: Lijie
authors.initials: L
authors.lastname: He
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Miao
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Changcun
authors.initials: C
authors.lastname: Guo
authors.forename: Zengfu
authors.initials: Z
authors.lastname: Xue
authors.forename: Weijia
authors.initials: W
authors.lastname: Dou
authors.forename: Fengrong
authors.initials: F
authors.lastname: Hu
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; D017931:DNA Primers; C103814:MYH9 protein, human; D035683:MicroRNAs; D020409:Molecular Motor Proteins; C487931:mirnlet7 microRNA, human; D018995:Myosin Heavy Chains