Y Tang1,2, X Meng2, X Yu2, H Shang1, S Chen2, L Liao3, J Dong4. 1. Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, Shandong Province, People's Republic of China. 2. Department of Endocrinology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, People's Republic of China. 3. Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250014, Shandong Province, People's Republic of China. liaolin@sdu.edu.cn. 4. Department of Endocrinology, Qilu Hospital of Shandong University, No. 107, Wenhua West Road, Jinan, 250012, Shandong Province, People's Republic of China. cwc_ll@sdu.edu.cn.
Abstract
BACKGROUND AND AIM: Poorly differentiated thyroid carcinoma (PDTC) is an endocrine malignancy that is challenging to treat due to its limited radioiodine uptake. microRNAs (miRNAs or miRs) have been shown to be useful in treating many types of tumors, including PDTC. This study aims to evaluate the potential effect of miR-875-5p on the radioiodine uptake of PDTC and to clarify the underlying mechanisms. METHODS: Expression of miR-875-5p and sodium-iodide symporter (NIS) in tissues and cell lines was determined using RT-qPCR. The binding relationship between miR-875-5p and NIS was predicted through in silico analysis and verified by dual-luciferase reporter gene assay. A series of miR-875-5p mimic, miR-875-5p inhibitor, shRNA against NIS, and overexpressed NIS plasmids were introduced into PDTC cells. We then evaluated the cell viability, colony formation, apoptosis, and radioiodine uptake of each PDTC sample via CCK-8 assay, clonogenic assay, flow cytometry, and γ counter, respectively. RESULTS: miR-875-5p was found to be highly expressed, but NIS was poorly expressed in DTC tissues and PDTC cell lines. NIS was verified to be a target gene of miR-875-5p. Upregulation of miR-875-5p was found to induce PDTC cell proliferation, and reduce apoptosis and radioiodine uptake in vitro through down-regulation of NIS. In an in vivo orthotopic model, the enhancement of miR-875-5p led to the reduction of NIS expression and radioiodine uptake in the thyroid tumors. CONCLUSIONS: Altogether, the findings of the current study suggest that down-regulated miR-875-5p expression could promote its target gene NIS to increase radioiodine uptake in PDTC, constituting a preventive strategy against PDTC.
BACKGROUND AND AIM: Poorly differentiated thyroid carcinoma (PDTC) is an endocrine malignancy that is challenging to treat due to its limited radioiodine uptake. microRNAs (miRNAs or miRs) have been shown to be useful in treating many types of tumors, including PDTC. This study aims to evaluate the potential effect of miR-875-5p on the radioiodine uptake of PDTC and to clarify the underlying mechanisms. METHODS: Expression of miR-875-5p and sodium-iodide symporter (NIS) in tissues and cell lines was determined using RT-qPCR. The binding relationship between miR-875-5p and NIS was predicted through in silico analysis and verified by dual-luciferase reporter gene assay. A series of miR-875-5p mimic, miR-875-5p inhibitor, shRNA against NIS, and overexpressed NIS plasmids were introduced into PDTC cells. We then evaluated the cell viability, colony formation, apoptosis, and radioiodine uptake of each PDTC sample via CCK-8 assay, clonogenic assay, flow cytometry, and γ counter, respectively. RESULTS: miR-875-5p was found to be highly expressed, but NIS was poorly expressed in DTC tissues and PDTC cell lines. NIS was verified to be a target gene of miR-875-5p. Upregulation of miR-875-5p was found to induce PDTC cell proliferation, and reduce apoptosis and radioiodine uptake in vitro through down-regulation of NIS. In an in vivo orthotopic model, the enhancement of miR-875-5p led to the reduction of NIS expression and radioiodine uptake in the thyroid tumors. CONCLUSIONS: Altogether, the findings of the current study suggest that down-regulated miR-875-5p expression could promote its target gene NIS to increase radioiodine uptake in PDTC, constituting a preventive strategy against PDTC.
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