title: MicroRNA 375 mediates the signaling pathway of corticotropin-releasing factor (CRF) regulating pro-opiomelanocortin (POMC) expression by targeting mitogen-activated protein kinase 8.
abstract: 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.
authors: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors: Nan
authors: N
authors: Zhang
authors: Jun-kai
authors: JK
authors: Lin
authors: Juan
authors: J
authors: Chen
authors: Xiong-fei
authors: XF
authors: Liu
authors: Jia-li
authors: JL
authors: Liu
authors: Hao-shu
authors: HS
authors: Luo
authors: Yue-qin
authors: YQ
authors: Li
authors: Sheng
authors: S
authors: Cui
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; C540349:Mirn375 microRNA, mouse; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8