hTERT基因沉默可阻断间变性甲状腺癌细胞的生长和迁移。

Silencing of hTERT blocks growth and migration of anaplastic thyroid cancer cells.

作者信息

Maggisano Valentina, Celano Marilena, Lombardo Giovanni Enrico, Lepore Saverio Massimo, Sponziello Marialuisa, Rosignolo Francesca, Verrienti Antonella, Baldan Federica, Puxeddu Efisio, Durante Cosimo, Filetti Sebastiano, Damante Giuseppe, Russo Diego, Bulotta Stefania

机构信息

Department of Health Sciences, "Magna Graecia" University of Catanzaro, 88100 Catanzaro, Italy.

Department of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, 00161 Rome, Italy.

出版信息

Mol Cell Endocrinol. 2017 Jun 15;448:34-40. doi: 10.1016/j.mce.2017.03.007. Epub 2017 Mar 10.

DOI:10.1016/j.mce.2017.03.007

PMID:28288903

Abstract

Mutations in the hTERT promoter responsible for constitutive telomerase activity are the most frequent genetic alteration detected in anaplastic thyroid cancer (ATC), and proposed as diagnostic and prognostic biomarker in these tumours. In this study we analyzed hTERT expression in a series of human ATCs and investigated the effects of small-interfering RNA-mediated silencing of hTERT on viability and migration and invasive properties of three human ATC cell lines. Expression of hTERT mRNA resulted increased in 8/10 ATCs compared to normal thyroid tissues. Silencing of hTERT in CAL-62, 8505C and SW1736 cells did not modify telomere length but determined a significant decrease (about 50%) of cell proliferation in all cell lines and a great reduction (about 50%) of migration and invasion capacity. These finding demonstrate that hTERT may be considered as a molecular target for ATC treatment.

摘要

导致组成型端粒酶活性的hTERT启动子突变是间变性甲状腺癌（ATC）中检测到的最常见的基因改变，并被提议作为这些肿瘤的诊断和预后生物标志物。在本研究中，我们分析了一系列人类ATC中的hTERT表达，并研究了小干扰RNA介导的hTERT沉默对三种人类ATC细胞系的活力、迁移和侵袭特性的影响。与正常甲状腺组织相比，8/10的ATC中hTERT mRNA表达增加。在CAL-62、8505C和SW1736细胞中沉默hTERT并没有改变端粒长度，但所有细胞系中的细胞增殖均显著降低（约50%），迁移和侵袭能力也大幅降低（约50%）。这些发现表明，hTERT可被视为ATC治疗的分子靶点。