title: miR-126-3p Inhibits Thyroid Cancer Cell Growth and Metastasis, and Is Associated with Aggressive Thyroid Cancer.
abstract: BACKGROUND
  Previous studies have shown that microRNAs are dysregulated in thyroid cancer and play important roles in the post-transcriptional regulation of target oncogenes and/or tumor suppressor genes.
  
  
  RESULTS
  We studied the function of miR-126-3p in thyroid cancer cells, and as a marker of disease aggressiveness. We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort. In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas. Mechanistically, ectopic overexpression of miR-126-3p significantly inhibited thyroid cancer cell proliferation, in vitro (p<0.01) and in vivo (p<0.01), colony formation (p<0.01), tumor spheroid formation (p<0.05), cellular migration (p<0.05), VEGF secretion and endothelial tube formation, and lung metastasis in vivo. We found 14 predicted target genes, which were significantly altered upon miR-126-3p transfection in thyroid cancer cells, and which are involved in cancer biology. Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to demonstrate that miR-126-3p has a tumor-suppressive function in thyroid cancer cells, and is associated with aggressive disease phenotype.
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: Shweta
authors.initials: S
authors.lastname: Kotian
authors.affiliation: Department of Surgery, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Zeiger
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: D051722:ADAM Proteins / Q000235:genetics; D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D027283:Large Neutral Amino Acid-Transporter 1; C527111:MIRN126 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D051722:ADAM Proteins; C098339:ADAM9 protein, human