title: Down-regulation of the microRNA-99 family members in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  MicroRNA deregulation is a critical event in head and neck squamous cell carcinoma (HNSCC). Several microRNA profiling studies aimed at deciphering the microRNA signatures of HNSCC have been reported, but there tends to be poor agreement among studies. The objective of this study was to survey the published microRNA profiling studies on HNSCC, and to assess the commonly deregulated microRNAs in an independent sample set.
  
  
  METHODS
  Meta-analysis of 13 published microRNA profiling studies was performed to define microRNA signatures in HNSCC. Selected microRNAs (including members of miR-99 family) were evaluated in an independent set of HNSCC cases. The potential contributions of miR-99 family to the tumorigenesis of HNSCC were assessed by in vitro assays.
  
  
  RESULTS
  We identified 67 commonly deregulated microRNAs. The up-regulation of miR-21, miR-155, miR-130b, miR-223 and miR-31, and the down-regulation of miR-100, miR-99a and miR-375 were further validated in an independent set of HNSCC cases with quantitative RT-PCR. Among these validated microRNAs, miR-100 and miR-99a belong to the miR-99 family. Our in vitro study demonstrated that restoration of miR-100 to the HNSCC cell lines suppressed cell proliferation and migration, and enhanced apoptosis. Furthermore, ectopic transfection of miR-99 family members down-regulated the expression of insulin-like growth factor 1 receptor (IGF1R) and mechanistic target of rapamycin (mTOR) genes.
  
  
  CONCLUSIONS
  In summary, we described a panel of frequently deregulated microRNAs in HNSCC, including members of miR-99 family. The deregulation of miR-99 family contributes to the tumorigenesis of HNSCC, in part by targeting IGF1R and mTOR signaling pathways.
authors.affiliation: Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Zujian
authors.initials: Z
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yu
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
authors.forename: Ishrat
authors.initials: I
authors.lastname: Mahjabeen
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D007573:Jaw Neoplasms / Q000235:genetics / Q000378:metabolism; D015201:Meta-Analysis as Topic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C561679:MIRN99 microRNA, human; D035683:MicroRNAs; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases