title: MicroRNA-133a regulates the mRNAs of two invadopodia-related proteins, FSCN1 and MMP14, in esophageal cancer.
abstract: BACKGROUND
  FSCN1 and matrix metalloproteinase 14 (MMP14) are both invadopodia-related proteins. We herein elucidate the tumourigenicity of these proteins and identify novel therapeutic agents in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  FSCN1 and MMP14 were evaluated by immunohistochemistry and quantitative PCR, and microRNA (miR)-133a was also evaluated by PCR in surgical ESCC specimens. The roles of FSCN1, MMP14 and miR-133a were established in ESCC cells.
  
  
  RESULTS
  The expression of FSCN1 or MMP14 was an independent poor prognostic factor according to a multivariate analysis of immunohistochemistry, and their co-expression correlated with the poorest overall survival (OS) out of all the examined factors. Additionally, their mRNAs significantly correlated and both inversely correlated with miR-133a in surgical specimens. Transfection of a miR-133a mimic decreased the mRNA and protein levels of both FSCN1 and MMP14 in ESCC cells. The knockdown of FSCN1 or MMP14 and transfection of a miR-133a mimic inhibited the proliferation and invasion of ESCC cells. Patients with a lower miR-133a expression have a significantly poorer OS than those with a higher expression.
  
  
  CONCLUSIONS
  The combined expression of FSCN1 and MMP14 is associated with a poor prognosis, and miR-133a, which regulates their mRNAs, can serve as a strong tumour suppressor of ESCC.
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Akanuma
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Hoshino
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Akutsu
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Isozaki
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Yusup
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Toyozumi
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Suito
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sekino
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: D002352:Carrier Proteins; C502658:FSCN1 protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14