Research Paper Volume 11, Issue 14 pp 5232—5245
Aberrant DNA methylation of synaptophysin is involved in adrenal cortisol-producing adenoma
- 1 Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 2 Department of Geriatrics, Institute of Aging and Age-related Disease Research, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 3 Department of Pathology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 4 Department of Otorhinolaryngology Head and Neck Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan, People’s Republic of China
- 5 Department of Urology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
Received: April 29, 2019 Accepted: July 19, 2019 Published: July 28, 2019
https://doi.org/10.18632/aging.102119How to Cite
Copyright © 2019 Zhong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cortisol-producing adenoma (CPA) is the main cause of Adrenal Cushing syndrome. However, its molecular mechanism is not fully understood. Previous study revealed Synaptophysin (SYP) is ubiquitously expressed in adrenocortical tumors, but its function in CPA still need to be discovered. In the present study we determine the molecular mechanism involved in SYP dysregulation in CPA and how SYP affects the secretion of cortisol in CPA. Our results showed that aberrant DNA methylation of SYP is involved in CPA progress. Using a miRNA microarray and qRT-PCR, we found decreased expression of miR-27a-5p in CPA compared with normal adrenal tissue. Moreover, the expression of TET3, the target gene of miR-27a-5p, increased in CPA compared with normal adrenal tissue. Knock-down of TET3 resulted in hypermethylation of SYP which reducing the expression level of SYP in H295R cells. The miR-27a-5p-TET3-SYP signalling pathway may regulate proliferation and cortisol secretion in H295R cells and, thus, play a key role in CPA development.