Expression of miR-100 and RBSP3 in FTC-133 cells after exposure to 131I.
BACKGROUND
Sodium iodide ((131)I) therapy for the management of differentiated thyroid cancer is based on the deposition of certain doses of ionizing radiation, which can modulate microRNA (miRNA, miR) expression. Recent studies have suggested that miR-100 is significantly differentially expressed between benign and malignant thyroid tissue samples and modulates retinoblastoma 1 serine phosphates from human chromosome 3 (RBSP3), which is involved in the regulation of cell growth and differentiation. Therefore, the authors tested the hypothesis that a potential mechanism of (131)I treatment affects miR-100, which in turn regulates RBSP3 to modulate cell proliferation in thyroid cancer in vitro.


METHODS
A follicular thyroid carcinoma cell line (FTC-133) was treated with (131)I or transfected with an oligonucleotide (miR-100 mimics, inhibitor, or negative control). Real-time quantitative PCR was used to confirm the expression levels of the miR-100 and RBSP3 mRNAs. Western blot analysis was performed to detect the levels of the RBSP3 protein. The cell cycle was analyzed on a cytofluorimeter by fluorescence-activated cell sorting analysis.


RESULTS
RBSP3 protein expression was detected in FTC-133 cells. (131)I treatment inhibited the expression of miR-100 in FTC cells, as assessed by real-time quantitative PCR analysis, whereas it upregulated the RBSP3 mRNA and protein. Overexpression and knockdown experiments indicated that miR-100 repressed the expression of the RBSP3 mRNA by blocking its translation. Overexpression of miR-100 led to the downregulation of the RBSP3 protein and promoted the transition of FTC cells from the G1 to the S phase, as assessed using FACS analysis.


CONCLUSIONS
(131)I treatment inhibited the expression of miR-100, which modulated RBSP3 in FTC cells. The new mechanism of suppression of the proliferation of FTC cells by I described here might occur through the downregulation of miR-100.
Departments of aNuclear Medicine bCardiac Surgery cGynecology and Obstetrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Shining
S
Zhang
Baoping
B
Deng
Yuanyuan
Y
Zhang
Ningyi
N
Jiang
D000328:Adult; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C486483:CTDSPL protein, human; D007457:Iodine Radioisotopes; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; D019275:Radiopharmaceuticals; D025521:Tumor Suppressor Proteins