Nasrpour Navaei Zahra, Taghehchian Negin, Zangouei Amir Sadra, Abbaszadegan Mohammad Reza, Moghbeli Meysam
Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2023;26(5):594-602. doi: 10.22038/IJBMS.2023.69174.15069.
Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid tumor type that has a poor prognosis due to its high therapeutic resistance. Since ATC accounts for half of thyroid cancer-related deaths, it is required to introduce novel therapeutic targets to increase survival in ATC patients. WNT and NOTCH signaling pathways are the pivotal regulators of cell proliferation and migration that can be regulated by microRNAs. We assessed the role of miR-506 in the regulation of cell migration, apoptosis, and drug resistance via NOTCH and WNT pathways in ATC cells.
The levels of miR-506 expressions were assessed in ATC cells and tissues. The levels of NOTCH, WNT, and EMT-related gene expressions were also assessed in miR-506 ectopic expressed cells compared with controls. Cell migration and drug resistance were also evaluated to assess the role of miR-506 in the regulation of ATC aggressiveness.
There were significant miR-506 down-regulations in ATC cells and clinical samples compared with normal cells and margins. MiR-506 suppressed NOTCH and WNT signaling pathways through LEF1, DVL, FZD1, HEY2, HES5, and HEY2 down-regulations, and APC and GSK3b up-regulations. MiR-506 significantly inhibited ATC cell migration and EMT (=0.028). Moreover, miR-506 significantly increased Cisplatin (=0.004), Paclitaxel (<0.0001), and Doxorubicin (=0.0014) sensitivities in ATC cells.
MiR-506 regulated EMT, cell migration, and chemoresistance through regulation of WNT and NOTCH signaling pathways in ATC cells. Therefore, after confirmation with animal studies, it can be introduced as an efficient novel therapeutic factor for ATC tumors.
间变性甲状腺癌（ATC）是一种侵袭性甲状腺肿瘤类型，因其具有高度治疗抗性，预后较差。由于ATC占甲状腺癌相关死亡人数的一半，因此需要引入新的治疗靶点以提高ATC患者的生存率。WNT和NOTCH信号通路是细胞增殖和迁移的关键调节因子，可受微小RNA调控。我们评估了miR-506在通过NOTCH和WNT通路调节ATC细胞的细胞迁移、凋亡和耐药性中的作用。
评估了ATC细胞和组织中miR-506的表达水平。与对照组相比，还评估了miR-506异位表达细胞中NOTCH、WNT和EMT相关基因的表达水平。还评估了细胞迁移和耐药性，以评估miR-506在调节ATC侵袭性中的作用。
与正常细胞和切缘相比，ATC细胞和临床样本中miR-506存在显著下调。miR-506通过下调LEF1、DVL、FZD1、HEY2、HES5和HEY2以及上调APC和GSK3b来抑制NOTCH和WNT信号通路。miR-506显著抑制ATC细胞迁移和EMT（P=0.028）。此外，miR-506显著提高了ATC细胞对顺铂（P=0.004）、紫杉醇（P<0.0001）和阿霉素（P=0.0014）的敏感性。
miR-506通过调节ATC细胞中的WNT和NOTCH信号通路来调节EMT、细胞迁移和化疗耐药性。因此，经动物研究证实后，它可作为一种有效的新型ATC肿瘤治疗因子引入。
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