title: Down-regulation of miR-218-2 and its host gene SLIT3 cooperate to promote invasion and progression of thyroid cancer.
abstract: BACKGROUND
  The functional relationships between intronic microRNAs (miRNAs) and their host genes in thyroid cancer remain unclear. miR-218, a miRNA down-regulated in several kinds of cancers and associated with multiple cancer phenotypes, is transcribed from 2 loci located on chromosomes 4p15.31 (miR-218-1) and 5q35.1 (miR-218-2) within the introns of SLIT2 and SLIT3, respectively.
  
  
  OBJECTIVE
  The aim of our work was to investigate the expression and the roles of miR-218-1 and miR-218-2, as well as their host genes SLIT2 and SLIT3 in thyroid carcinogenesis.
  
  
  METHODS
  The expression of miR-218-1 and miR-218-2, as well as their host genes SLIT2 and SLIT3, in a panel of normal and neoplastic human thyroid tissues was assessed by quantitative RT-PCR. We restored the expression of miR-218-2 and SLIT3 in thyroid cancer cells and evaluated their effects on cell invasion, migration, and proliferation.
  
  
  RESULTS
  We found that miR-218-2 and its host gene SLIT3 were down-regulated concomitantly in thyroid cancer. Synergistic inhibitory effects of miR-218-2 with SLIT3 on thyroid cancer cell invasion, migration, and proliferation were observed. Moreover, the effects of miR-218-2 on thyroid cancer cells were due, at least partially, to targeting PDGFRA and PLCG1.
  
  
  CONCLUSIONS
  These results implicate the involvement of miR-218-2 and its host gene SLIT3 in thyroid cancer cell invasion, migration, and proliferation. Our findings highlight the functional associations of intronic miRNAs and their host genes in thyroid carcinogenesis.
authors.affiliation: Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.forename: Gouhong
authors.initials: G
authors.lastname: Wei
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Donghong
authors.initials: D
authors.lastname: Fang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liao
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xiao
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D051966:Phospholipase C gamma / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C547471:MIRN218 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C498990:SLIT3 protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; C522157:PLCG1 protein, human; D051966:Phospholipase C gamma