Anaplastic thyroid carcinoma (ATC) is the most aggressive malignancy in thyroid cancers. Resistance to current therapies is still a challenge. MicroRNAs are a class of small non-coding RNAs, regulating gene expression. MiR-21 is an oncomiR that is overexpressed in nearly all cancers including ATC. Accumulating evidence suggested that miR-21 has a role in cancer stemness state, apoptosis, cell cycle progression, and differentiation. Therefore, we evaluated the application of Off-miR-21 to sequester the microRNA for therapeutic purposes on ATC cell lines. In this study, C643 and SW1736 were transducted by hsa-miR-21 antagomir (Off-miR-21). PTEN gene expression was performed as a known target of miR-21. Stemness state in cancer stem cells (CSCs) was evaluated by the changes of CSC biomarkers including Oct-4 and ABCG2. Apoptosis was assessed by PDCD4 and Mcl-1 gene expression and flow cytometry. Sodium/iodide symporter (NIS) and thyroglobulin (TG) were measured as ATC differentiation markers. In addition, cell cycle progression was investigated via the alterations of p21 gene expression and flow cytometry. Specific downregulation of miR-21 induced the differentiation and apoptosis in C643 and SW1736. Inversely, the treatment inhibited stemness state and cell cycle progression. Knockdown of miR-21 significantly increased the expression of PDCD4, p21, NIS, and TG while leading to decreased expression of Oct-4, ABCG2, and Mcl-1.Taken together, the results suggest that miR-21, as an oncomiR, has a role not only in stemness state but also in tumor growth, differentiation, and apoptosis. Hence, suppression of miR-21 could pave the way for ATC therapy.
Antisense-miR-21 Anaplastic thyroid cancer Apoptosis Differentiation Cancer stem cell
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The authors would like to thank Stem Cell Technology Research Center and Nuclear Medicine Research Center at Shariati Hospital which supported some parts of the experiments. The authors would like to acknowledge the assistance of Dr. Marzieh Ebrahimi, Dr. Mahin Nikogoftar, Dr. Amir Atashi, Mr. Mohsen Malehmir, and Mr. Majid Zakidizaji for their scientific advice and Dr. Mohsen Khorashadizadeh, Dr. Navid Madani, Prof. Anooshirvan Hedayat, Mr. Ehsan Janzamin, Mr. Fazel Samani, and Ms. Azadeh Anbarlou for their technical advice and support.
This project has been funded by National Elite Foundation of Allameh Tabatabai grant (BN012) and Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences.
Conflicts of interest
This article does not contain any studies with human participants or animals performed by any of the authors.
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