microRNA‐599 promotes apoptosis and represses proliferation and epithelial‐mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2‐depentent Notch signaling pathway

Abstract Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA‐599 (miR‐599) on proliferation, apoptosis, and epithelial‐mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual‐luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR‐599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR‐559. In addition, the expression of Bax and E‐cadherin was elevated while that of Hey2, Notch1, Delta‐like1, Hes1, N1ICD, Jagged1, Snail, Slug, N‐cadherin and Vimentin, and Bcl‐2 was reduced in cells treated with upregulated miR‐599 or downregulated Hey2. Moreover, miR‐599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR‐599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.