title: MicroRNA-3666 Regulates Thyroid Carcinoma Cell Proliferation via MET.
abstract: OBJECTIVE
  Thyroid carcinoma (TC) is a highly lethal malignant cancer and its carcinogenesis remains undetermined. Dysregulation of microRNAs (miRNAs) is well known to be involved in the development of various cancers, including TC, whereas a role of miR-3666 in the pathogenesis of TC has not been appreciated.
  
  
  METHODS
  We analyzed the levels of MET and miR-3666 in TC tissue and the relationship of miR-3666 levels with patients' prognosis. We then overexpressed miR-3666 by miRNA mimics transfection and inhibited miR-3666 by miRNA antisense transfection in TC cells. Cell survival and growth were analyzed by CCK-8 assay and MTT assay, respectively. Cell apoptosis and proliferation were analyzed by flow cytometry. Bioinformatics analyses were applied to predict miR-3666 targets, which was then confirmed using luciferase reporter assay.
  
  
  RESULTS
  We detected significantly higher levels of MET, and significantly lower levels of miR-3666 in TC tissue, compared to the adjacent non-tumor tissue. Moreover, the low miR-3666 levels were associated with poor survival of the patients. Overexpression of miR-3666 significantly inhibited cell growth, while depletion of miR-3666 increased cell growth in TC cells. Moreover, the effects of miR-3666 on cell growth appeared to result from alteration in cell proliferation, rather than changes in cell apoptosis. MiR-3666 was found to bind to the 3'-UTR of MET mRNA to inhibit its translation in TC cells.
  
  
  CONCLUSIONS
  Reduced miR-3666 levels in TC tissue may promotes TC growth, possibly through MET-mediated cell proliferation.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Chengzhong
authors.initials: C
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; C000612604:MIRN3666 microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met