MicroRNA 375 Mediates the Signaling Pathway of Corticotropin-releasing Factor (CRF) Regulating Pro-opiomelanocortin (POMC) Expression by Targeting Mitogen-activated Protein Kinase 8

作者：Nan Zhang, Jun-Kai Lin, Juan Chen, Xiongfei Liu, Jiali Liu, Haoshu Luo, Yueqin Li, Sheng Cui · 发表于：Journal of Biological Chemistry · 年份：2013 · DOI：10.1074/jbc.m112.425504 · 被引用次数：75 · 研究领域：MicroRNA in disease regulation、Nuclear Receptors and Signaling、Regulation of Appetite and Obesity

Pro-opiomelanocortin (POMC) is a common precursor of melanocortin-related peptides in the pituitary and primarily regulated by corticotropin- releasing factor (CRF). Our results show that miR-375 is highly expressed in the mouse pituitary gland and located specifically in the intermediate lobe of pituitary. The functional studies show that the forced inhibition of endogenous miR-375 in AtT-20 mouse pituitary tumor cells and in the intermediate lobe of the pituitary gland significantly increases POMC expression, whereas miR-375 overexpression down-regulates POMC expression and ACTH secretion stimulated by CRF. This function of miR-375 is accomplished by its binding to the 3'-UTR of mitogen-activated protein kinase kinase kinase-8. Our results here have demonstrated that miR-375 acts as a negative regulating molecule mediating the signaling pathway of CRF and affecting POMC expression by targeting mitogen-activated protein kinase kinase kinase-8, which subsequently down-regulates ERK1/2 phosphorylation and nerve growth factor-induced clone B (NGFI-B) transcription activity. Taken together, our results show that miR-375 is a novel negative regulator of POMC expression and related hormone secretion.