TY - JOUR ID - 21869 TI - MicroRNA-506 as a tumor suppressor in anaplastic thyroid carcinoma by regulation of WNT and NOTCH signaling pathways JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Nasrpour Navaei, Zahra AU - Taghehchian, Negin AU - Zangouei, Amir Sadra AU - Abbaszadegan, Mohammad reza AU - Moghbeli, Meysam AD - Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AD - Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AD - Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Y1 - 2023 PY - 2023 VL - 26 IS - 5 SP - 594 EP - 602 KW - Anaplastic thyroid - carcinoma KW - Chemo resistance KW - EMT KW - miR-506 KW - NOTCH KW - WNT DO - 10.22038/ijbms.2023.69174.15069 N2 - Objective(s): 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.Materials and Methods: 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. Results: 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 (P=0.028). Moreover, miR-506 significantly increased Cisplatin (P=0.004), Paclitaxel (P<0.0001), and Doxorubicin (P=0.0014) sensitivities in ATC cells. Conclusion: 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.  UR - https://ijbms.mums.ac.ir/article_21869.html L1 - https://ijbms.mums.ac.ir/article_21869_cd0c932cda5eb42ca1f94ae4be20c94e.pdf ER -