title: Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma.
abstract: BACKGROUND
  On the basis of the microRNA (miRNA) expression signature of maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-874 was significantly reduced in cancer cells. We focused on the functional significance of miR-874 in cancer cells and identification of miR-874-regulated novel cancer networks in MSSCC.
  
  
  METHODS
  We used PCR-based methods to investigate the downregulated miRNAs in clinical specimens of MSSCC. Our signature analyses identified 23 miRNAs that were significantly reduced in cancer cells, such as miR-874, miR-133a, miR-375, miR-204, and miR-1. We focused on miR-874 as the most downregulated novel miRNA in our analysis.
  
  
  RESULTS
  We found potential tumour suppressive functions such as inhibition of cancer cell proliferation and invasion. A molecular target search of miR-874 revealed that PPP1CA was directly regulated by miR-874. Overexpression of PPP1CA was observed in MSSCC clinical specimens. Silencing of the PPP1CA gene significantly inhibited cancer cell proliferation and invasion.
  
  
  CONCLUSIONS
  The downregulation of miR-874 was a frequent event in MSSCC, which suggests that miR-874 functions as a tumour suppressive miRNA, directly regulating PPP1CA that has a potential role of an oncogene. The identification of novel miR-874-regulated cancer pathways could provide new insights into potential molecular mechanisms of MSSCC oncogenesis.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nohata
authors.forename: T
authors.initials: T
authors.lastname: Hanazawa
authors.forename: N
authors.initials: N
authors.lastname: Kikkawa
authors.forename: D
authors.initials: D
authors.lastname: Sakurai
authors.forename: L
authors.initials: L
authors.lastname: Fujimura
authors.forename: T
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: K
authors.initials: K
authors.lastname: Kawakami
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: H
authors.initials: H
authors.lastname: Enokida
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
authors.forename: A
authors.initials: A
authors.lastname: Katayama
authors.forename: Y
authors.initials: Y
authors.lastname: Harabuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: N
authors.initials: N
authors.lastname: Seki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008443:Maxillary Sinus; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D054645:Protein Phosphatase 1 / Q000235:genetics
chemical_list: C561946:MIRN874 microRNA, human; D035683:MicroRNAs; C517187:PPP1CA protein, human; D054645:Protein Phosphatase 1