Nuclear-targeted EGF receptor enhances proliferation and migration of human anaplastic thyroid cancer cells.

INTRODUCTION: Epidermal growth factor (EGF) has various important physiological functions, which it exerts by binding to the epidermal growth factor receptor (EGFR). Reports show that EGF expression is strongly correlated with the occurrence and development of many types of tumour. To date, however, the relationship between EGF/EGFR and the occurrence and development of thyroid carcinoma remains unclear. MATERIAL AND METHODS: In the current study, we investigated this phenomenon using human anaplastic thyroid carcinoma cell lines (SUN-80). RESULTS: The results indicated that EGF triggered the EGFR-mediated intracellular signalling pathway, including signal transducers and activators of transcription 1/3/5 (STAT1/3/5) and protein kinase B (AKT) in a time- and dose-dependent manner. In addition, results from EGF-induced EGFR internalization and co-localization analyses showed that clathrin, Rab5/7, and EEA1 play critical roles in the intracellular trafficking of EGF/EGFR. Interestingly, EGF triggered EGFR translocation into the nucleus, while nuclear-localized EGFR affected cell cycle distribution, thereby significantly promoting the ration of S phase. Overall, these findings indicated that nuclear EGFR exerts biological activity and physiological functions, including changing cell cycle, which in turn promotes proliferation and migration of SUN-80 cells. CONCLUSION: These findings lay a foundation for further explorations seeking to understand the biological effects of the EGF/EGFR system on the occurrence and development of thyroid cancer.

Hypomethylation of Rnase6 Promoter Enhances Proliferation and Migration of Murine Aortic Vascular Smooth Muscle Cells and Aggravates Atherosclerosis in Mice.

Background: Accumulating evidence has implicated DNA methylation in the progression of atherosclerosis (AS). Rnase6 has been reported to be upregulated in AS development, but the specific regulatory mechanism remains unclear. Material/Methods: Peripheral blood and sclerotic plaque tissues from 25 AS patients were collected to detect Rnase6 expression. Methylation-specific polymerase chain reaction (MSP) was used to detected Rnase6 methylation levels in the peripheral blood of AS patients. Rnase6 expression was knocked down or DNA methyltransferase 1 (DNMT1) was overexpressed in OX-LDL-treated mouse aortic smooth muscle cells (MOVAS), and cell proliferation, migration, ROS content, and inflammatory factor secretion levels were detected. 740 Y-P, a PI3K specific agonist, was introduced to verify the effect of Rnase6 promoter hypomethylation on the PI3K/Akt signaling pathway. We knocked down Rnase6 expression in ApoE-/- mice fed with a high-fat diet to examine Rnase6 promoter methylation levels. Plaque areas and inflammatory factor secretion were examined in AS mice overexpressing DNMT1. Results: Rnase6 expression was upregulated in the peripheral blood and plaque tissues of AS patients, accompanied by decreased methylation levels of the Rnase6 promoter. Interfering with Rnase6 expression or overexpressing DNMT1 in OX-LDL stimulated MOVAS inhibited cell proliferation and migration, decreased ROS content and inflammatory factor secretion, and inhibited PI3K pathway protein expression. Rnase6 expression was decreased in the peripheral blood and plaque tissues of si-Rnase6-injected mice, and Rnase6 promoter methylation was increased. Mice overexpressing DNMT1 showed less plaque areas in the aortic root and lower secretion levels of inflammatory factors. Conclusion: Hypomethylation of the promoter of Rnase6 enhanced the proliferation and migration of OX-LDL treated MOVAS, upregulated ROS content and inflammatory factor secretion levels in the cells, and activated the PI3K/Akt signaling pathway.