Epigenetic Modifications in Thyroid Cancer Cells Restore NIS and Radio-Iodine Uptake and Promote Cell Death.
Epigenetic Modifications in Thyroid Cancer Cells Restore NIS and Radio-Iodine Uptake and Promote Cell Death.
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DOI：
10.3390/jcm7040061
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发表时间：
2018-03-21
影响因子：
3.9
通讯作者：
Di Fazio P
中科院分区：
文献类型：
--
作者：
Wächter S;Damanakis AI;Elxnat M;Roth S;Wunderlich A;Verburg FA;Fellinger SA;Bartsch DK;Di Fazio P
表观遗传修饰被认为是导致甲状腺组织去分化及其恶变的原因。体外研究了泛去乙酰酶抑制剂Panobinostat、SAHA和Trichostatin A(TSA)、钠碘转运体(NIS；SLC5A5)、甲状腺转录因子1(TTF1)、高迁移率族A2(HMGA2)和H19对细胞增殖的抑制作用及其可能的靶向miRNAs。用实时细胞分析仪xCELLigence检测5种甲状腺癌细胞系(FTC133、TPC1、bCPAP、8505C、C643)的细胞活力。RT-qPCR和Western Blot检测上述标志物的表达。放射性碘摄取用~(131)I伽玛计数器测定。治疗后，所有五种细胞系的细胞存活率均下降。10 NM Panobinostat、1µM TSA或10µM SAHA可引起5种细胞株NIS转录显著上调，而NIS蛋白仅在FTC133、bCPAP和C643细胞中表达上调。10 nM潘诺比妥和1µM TSA处理FTC133和C643细胞48h后，FTC133和C643细胞对放射性碘的摄取增加。除了用1微米TSA处理的TPC1细胞外，在所有五种细胞系中都检测到癌基因HMGA2的显著下调。相应地，hsa-let-7b-5p和hsa-let-7f-5p在所有细胞系中稳定或显著过表达，但10µM SAHA处理的TPC1细胞除外。TTF1在FTC133、bCPAP和8505C细胞中显著下调，而TPC1和C643则上调或稳定表达。TTF1在人未分化甲状腺癌组织中高表达，而在滤泡性甲状腺癌组织中表达下调，在乳头状甲状腺癌组织中检测不到。H19在48h后呈高表达，但用Panobinostat和SAHA处理的bCPAP细胞除外。H19在间变性、滤泡性和乳头状甲状腺肿瘤组织中表达不同。脱乙酰酶抑制剂降低了细胞存活率，恢复了NIS和H19，并抑制了癌基因HMGA2和TTF1。
Epigenetic modifications have been identified as being responsible for the de-differentiation of thyroid tissue and its malignant transformation. Cell proliferation inhibitory effects of the pan-deacetylase inhibitors panobinostat, SAHA and Trichostatin A (TSA), the modulation of the sodium iodide symporter (NIS; SLC5A5), thyroid transcription factor 1 (TTF1), high mobility group A2 (HMGA2), and H19 and their putative targeting miRNAs have been evaluated in vitro. The cell viability was measured in five thyroid cancer cell lines (FTC133, TPC1, BCPAP, 8505C, C643) by real time cell analyzer xCELLigence. Expression of the above mentioned markers was performed by RT-qPCR and Western Blot. Radioiodine up-take was detected by Gamma Counter with I131. Cell viability decreased after treatment in all five cell lines. 10 nM panobinostat; 1 µM TSA or 10 µM SAHA caused a significant over-expression of NIS transcript in all five cell lines, whereas NIS protein was up-regulated in FTC133, BCPAP, and C643 cell lines only. Radioiodine up-take increased in FTC133 and C643 cells after 48 h of treatment with 10 nM panobinostat and 1 µM TSA. A significant down-regulation of the oncogene HMGA2 was detected in all five cell lines; except for TPC1 cells that were treated with 1 µM TSA. In accordance, hsa-let-7b-5p and hsa-let-7f-5p were stable or significantly over-expressed in all of the cell lines, except for TPC1 cells that were treated with 10 µM SAHA. TTF1 was significantly down-regulated in FTC133, BCPAP, and 8505C cells; whereas, TPC1 and C643 showed an up-regulated or stable expression. TTF1 was over-expressed in samples of human anaplastic thyroid cancer; whereas, it was down-regulated in follicular and undetectable in papillary thyroid cancer. H19 was over-expressed after 48 h treatment, except for BCPAP cells that were treated with panobinostat and SAHA. H19 was differently expressed in human anaplastic, follicular and papillary thyroid tumor samples. Deacetylase inhibitors reduced cell viability, restored NIS and H19, and suppressed the oncogenes HMGA2 and TTF1 in thyroid cancer cells.
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影响因子：
--
作者：
Bernhart E;Stuendl N;Kaltenegger H;Windpassinger C;Donohue N;Leithner A;Lohberger B
通讯作者：
Lohberger B
影响因子：
4.8
作者：
Furuya, F;Shimura, H;Kobayashi, T
通讯作者：
Kobayashi, T
影响因子：
50.3
作者：
Fedele, Monica;Visone, Rosa;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
DOI：
10.1007/s00432-016-2138-z
发表时间：
2016-06-01
影响因子：
3.6
作者：
Damanakis, Alexander I.;Eckhardt, Sabine;Di Fazio, Pietro
通讯作者：
Di Fazio, Pietro
影响因子：
4.2
作者：
Gryder BE;Sodji QH;Oyelere AK
通讯作者：
Oyelere AK