Antisense-miR-21 enhances differentiation/apoptosis and reduces cancer stemness state on anaplastic thyroid cancer.
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.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Dr. Shariati Hospital, North Kargar Ave., Tehran, 14114, Iran.
Vahid
V
Haghpanah
Department of Laboratory Science, Faculty of Allied Medicine, Alborz University of Medical Sciences, Karaj, Iran.
Parviz
P
Fallah
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
Rezvan
R
Tavakoli
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.|Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mahmood
M
Naderi
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Dr. Shariati Hospital, North Kargar Ave., Tehran, 14114, Iran.
Hilda
H
Samimi
Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Masoud
M
Soleimani
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Dr. Shariati Hospital, North Kargar Ave., Tehran, 14114, Iran. emrc@tums.ac.ir.
Bagher
B
Larijani
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology*; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C579095:MCL1 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016376:Oligonucleotides, Antisense; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins
Anaplastic thyroid cancer; Antisense-miR-21; Apoptosis; Cancer stem cell; Differentiation