title: miR-219-5p modulates cell growth of papillary thyroid carcinoma by targeting estrogen receptor α.
abstract: BACKGROUND
  Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. It has been demonstrated that micro-RNAs (miRNAs) are involved in the development of PTC. The miRNA-chromatin immunoprecipitation microarray assay revealed down-regulation of miR-219-5p; however, the effect of miR-219-5p on PTC cell growth remains unknown. This result implied the critical role of miR-219-5p in the development of PTC.
  
  
  METHODS
  We investigated the association between miR-219-5p and PTC development. Expression of miR-219-5p was monitored in 30 PTC tissue specimens and compared with that in 30 normal thyroid tissue specimens. The effect of miR-219-5p on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanism was clarified by a reporter assay and rescue experiment.
  
  
  RESULTS
  The current study confirmed that miR-219-5p expression was inhibited in PTC tissue samples. There were statistically significant differences in the expression of miR-219-5p with regard to sex, tumor size, and lymph node metastasis in patients with PTC. Forced expression of miR-219-5p suppressed PTC cell proliferation and migration and promoted apoptosis. Further study showed that estrogen receptor (ER) α was the direct target of miR-219-5p and mediated the effect of miR-219-5p on PTC occurrence. Expression of miR-219-5p was inversely correlated with that of ERα. Importantly, ERα overexpression in PTC cells rescued the inhibitory effect of miR-219-5p on PTC cell proliferation and migration. Thus, our results indicated that miR-219-5p played a critical role in PTC growth by inhibiting ERα.
  
  
  CONCLUSIONS
  Our investigation identified miR-219-5p as a negative regulator of PTC development through targeting of ERα.
authors.affiliation: Department of Endocrinology and Metabolism and Department of General Surgery (C.H., Y.L. Y.P., H.X.), Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 200080, China; Department of Endocrinology and Metabolism (Z.C., X.Z., B.T., Y.C., X.W., Z.Q., H.X.), Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Department of Medical Oncology (Q.Z.), Fudan University Shanghai Cancer Center (M.H.); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Nuclear Medicine or Institute of Oncology (C.M.), The Hospital Affiliated to Jiangsu University, Zhenjiang 212001, China; Department of Urology (Q.Z.), Shanghai Traditional Chinese and Medicine Integrated Hospital, Shanghai 200082, China; and Department of Endocrinology and Metabolism (L.Y.), Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Zhaogeng
authors.initials: Z
authors.lastname: Cai
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Huang
authors.forename: Chaoming
authors.initials: C
authors.lastname: Mao
authors.forename: Qifa
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Bi
authors.initials: B
authors.lastname: Tang
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Qian
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Yongde
authors.initials: Y
authors.lastname: Peng
authors.forename: Huanbai
authors.initials: H
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; C578248:MIRN219 microRNA, human; D035683:MicroRNAs