Pituitary adenoma-induced IGF-I triggers uncontrolled proliferation and malignant transformation of thyroid cells through facilitating pre-miR-3613 processing

Pituitary adenoma (PA) is a chronic endocrine disease leading to various physiological abnormities. Our previous study has revealed that PA would result in thyroid diseases including goiter and thyroid cancer, which are caused by uncontrolled proliferation and malignant transformation of thyroid cells. However, the mechanism of PA inducing thyroid diseases remains unclear. Our recent study has indicated that insulin-like growth factor I (IGF-I) might be positively correlated with thyroid diseases in PA patients. Therefore, the primary aim of this study was to investigate the mechanism of PA-induced IGF-I triggering uncontrolled proliferation and malignant transformation of thyroid cells. In this study, small RNA sequencing was performed to explore IGF-I-modified miRNAs, and miRNA pulldown was used to detect miRNA-mRNA interaction. Besides, RNA antisense purification (RAP) was utilized to identify RNA-protein association while nude mice xenograft tumor model was established to determine the tumorigenicity of IGF-I-treated thyroid cells in vivo. Herein, the current study confirmed that IGF-I was positively associated with thyroid diseases in PA patients. Besides, IGF-I increased miR-3613-3p level through facilitating pre-miR-3613 processing by decreasing monocyte chemoattractant protein-induced protein 1 (MCPIP1) expression in thyroid cells. Moreover, IGF-I promoted proliferation and suppressed apoptosis of thyroid cells by inhibiting Killin (KLLN) and Bcl-2-like protein 11 (BCL2L11) via miR-3613-3p. In addition, IGF-I induced malignant transformation of thyroid cells by inhibiting KLLN via miR-3613-3p. These findings uncovered exact mechanisms of PA-induced IGF-I regulating uncontrolled proliferation and malignant transformation of thyroid cells, which should provide potential therapeutic targets for thyroid diseases in PA.