title: Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression.
abstract: Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na(+)/I(-) symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC).
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Luchuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lv
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Qihe People's Hospital, Qihe, Shandong 251100, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
authors.affiliation: Department of General Surgery, Licheng District People's Hospital, Jinan, Shandong 250115, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Caoxian People's Hospital, Caoxian, Shandong 274400, China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, China.
authors.forename: Shan
authors.initials: S
authors.lastname: He
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, China. Electronic address: qingdz0201@163.com.
authors.forename: Qingdong
authors.initials: Q
authors.lastname: Zeng
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D000099209:Sodium-Iodide Symporters
chemical_list: D017931:DNA Primers; D006655:Histone Deacetylases; D007457:Iodine Radioisotopes; D035683:MicroRNAs; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C542542:MIRN146 microRNA, human
keywords: Dedifferentiated thyroid carcinoma; Histone deacetylase; Na(+)/I(−) symporter; Radioiodine-sensitivity; miR-146b