title: Papillary thyroid cancer-derived exosomes contain miRNA-146b and miRNA-222.
abstract: BACKGROUND
  With the increasing diagnosis of indolent papillary thyroid cancer (PTC), the task of identifying those likely to suffer from recurrence is becoming ever more challenging. MicroRNA (miRNA/miR) in the circulation has been demonstrated as potential biomarkers of recurrence in PTC. This study aimed to investigate in vitro if extracellular miRNAs are contained in exosomes, and their potential effect on other cells.
  
  
  METHODS
  TPC-1 (PTC) and NTHY (normal thyroid follicular) cell lines were treated with exosome isolates and conditioned medium (CM), both containing miR-146b and miR-222. The changes in proliferation over a 72-h period of TPC-1 and NTHY were compared. Student t-test and analysis of variance were used for significance testing, and P < 0.05 was considered significant.
  
  
  RESULTS
  Exosomes derived from TPC-1 cells were demonstrated to contain miR-146b and miR-222 in relative abundance. These exosomes caused a negative proliferative effect on both TPC-1 and NTHY cells. Exosomes derived from NTHY cells did not exert a significant proliferative effect on either cell line. CM from both cell types caused an initial increase in TPC-1 proliferation at 24 h. No significant change in proliferation was seen with NTHY cells when treated with either of the CM.
  
  
  CONCLUSIONS
  The results showed that PTC cells overexpress miR-146b and miR-222 in exosomes; and that factors released by both normal thyroid and PTC cells alter proliferation of other cells in a complex manner. The intercellular interactions were likely conferred in part by exosomal miRNA, which can potentially be developed as biomarkers of PTC recurrence.
authors.affiliation: Monash University Endocrine Surgery Unit, The Alfred Hospital, Melbourne, Victoria, Australia; Department of Surgery, Monash University, Melbourne, Victoria, Australia; Department of Surgery, University of Sydney, New South Wales, Australia. Electronic address: Lee.JamesC@gmail.com.
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Surgery, University of Sydney, New South Wales, Australia; Kolling Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Jing-Ting
authors.initials: JT
authors.lastname: Zhao
authors.affiliation: Department of Surgery, University of Sydney, New South Wales, Australia; Kolling Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Justin
authors.initials: J
authors.lastname: Gundara
authors.affiliation: Monash University Endocrine Surgery Unit, The Alfred Hospital, Melbourne, Victoria, Australia; Department of Surgery, Monash University, Melbourne, Victoria, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Serpell
authors.affiliation: Department of Endocrinology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Leon A
authors.initials: LA
authors.lastname: Bach
authors.affiliation: Department of Surgery, University of Sydney, New South Wales, Australia; Kolling Institute of Medical Research, Sydney, New South Wales, Australia; University of Sydney Endocrine Surgery Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Stan
authors.initials: S
authors.lastname: Sidhu
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055354:Exosomes / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D035683:MicroRNAs; C542542:MIRN146 microRNA, human; C525710:MIR222, human
keywords: Biomarkers; Exosomes; MicroRNA; PTC; Papillary thyroid cancer; miR-146b; miR-222