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Melatonin is a key hormone regulating daily and seasonal rhythms, in which a variety of positive and negative regulatory factors, such as norepinephrine (NE) and leptin, are involved. However, the interactions among these factors and the mechanisms remain to be elucidated. The aims of the present study were to identify the functions and the related mechanisms of miR\u20107 in regulating melatonin synthesis and secretion through in vitro and in vivo experiments in pineal gland of pigs, which is an important animal model for agricultural and biomedical studies. Our results firstly show that miR\u20107 is specifically expressed in porcine pinealocytes and negatively regulates melatonin synthesis. The further functional studies show that the dynamic expression levels of miR\u20107 are contrary to the melatonin levels throughout the day, and the forced inhibition of endogenous miR\u20107 in porcine pinealocytes sharply increases arylalkylamine <jats:italic>N<\/jats:italic>\u2010acetyltransferase (AANAT) expression by 80.0% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0031) and melatonin levels by 81.0% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0421), whereas miR\u20107 over\u2010expression down\u2010regulates AANAT expression by 38.6% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0004) and melatonin levels by 37.6% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0212). In addition, the miR\u20107 expression is up\u2010regulated by leptin through the JAK\/STAT3 signaling pathway, and the in vivo intracerebroventricular injection of leptin increases miR\u20107 expression by 80.0% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0044) in porcine pineal glands and reduces melatonin levels by 57.1% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0060) compared with the controls. This functional inhibition of melatonin synthesis by miR\u20107 is accomplished by its binding to the 3\u2032\u2010UTR of <jats:italic>Raf1<\/jats:italic>. Further, our results demonstrate that the RAF1\/MEK\/ERK signaling pathway mediates NE\u2010induced AANAT expression, whereas leptin attenuates NE's function through miR\u20107. Taken together, the results demonstrated that leptin activates the JAK\/STAT3 signaling pathway to increase the expression of miR\u20107, which acts as a negative regulatory molecule inhibiting NE\u2010activated RAF1\/MEK\/ERK signaling pathway by targeting <jats:italic>Raf1<\/jats:italic>, resulting in decreased AANAT expression and melatonin synthesis. These findings suggest that miR\u20107 is a novel negative regulator of melatonin synthesis and links leptin\u2010 and NE\u2010mediated signaling pathways in porcine pineal glands, which will contribute to our understanding in the establishment of the biological rhythms resulting from melatonin.<\/jats:p>","DOI":"10.1111\/jpi.12552","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T04:41:11Z","timestamp":1547008871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["MicroRNA\u20107 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland"],"prefix":"10.1111","volume":"66","author":[{"given":"Jingtao","family":"Qiu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Joint International Research Laboratory of Agriculture and Agri\u2010Product Safety, the Ministry of Education of China Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Joint International Research Laboratory of Agriculture and Agri\u2010Product Safety, the Ministry of Education of China Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewen","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences China Agricultural University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences China Agricultural University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjiao","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences China Agricultural University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology, College of Biological Sciences China Agricultural University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemian","family":"Gou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences Beijing 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