title: MiR-20a is upregulated in anaplastic thyroid cancer and targets LIMK1.
abstract: BACKGROUND
  There have been conflicting reports regarding the function of miR-20a in a variety of cancer types and we previously found it to be dysregulated in sporadic versus familial papillary thyroid cancer. In this study, we studied the expression of miR-20a in normal, benign and malignant thyroid samples, and its effect on thyroid cancer cells in vitro and in vivo.
  
  
  RESULTS
  The expression of miR-20a in normal, benign and malignant thyroid tissue was determined by quantitative RT-PCR. Thyroid cancer cells were transfected with miR-20a and the effect on cellular proliferation, tumor spheroid formation, and invasion was evaluated. Target genes of miR-20 were determined by genome-wide mRNA expression analysis with miR-20a overexpression in thyroid cancer cells and target prediction database. Target genes were validated by quantitative PCR and immunoblotting, and luciferase assays. MiR-20a expression was significantly higher in anaplastic thyroid cancer than in differentiated thyroid cancer, and benign and normal thyroid tissues. MiR-20a significantly inhibited thyroid cancer cell proliferation in vitro (p<0.01) and in vivo (p<0.01), tumor spheroid formation (p<0.05) and invasion (p<0.05) in multiple thyroid cancer cell lines. We found that LIMK1 was a target of miR-20a in thyroid cancer cell lines and direct knockdown of LIMK1 recapitulated the effect of miR-20a in thyroid cancer cells.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to demonstrate that miR-20a plays a role as a tumor suppressor in thyroid cancer cells and targets LIMK1. Our findings suggest the upregulated expression of miR-20a in anaplastic thyroid cancer counteracts thyroid cancer progression and may have therapeutic potential.
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006801:Humans; D054461:Lim Kinases / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D018874:Spheroids, Cellular / Q000473:pathology; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics* / Q000473:pathology*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: C534451:MIRN20a microRNA, human; D035683:MicroRNAs; C515892:LIMK1 protein, human; D054461:Lim Kinases