title: Hepatic MiR-291b-3p Mediated Glucose Metabolism by Directly Targeting p65 to Upregulate PTEN Expression.
abstract: Several studies have suggested an important role of miR-291b-3p in the development of embryonic stem cells. In previous study, we found that the expression of miR-291b-3p was significantly upregulated in the liver of db/db mice. However, the role of miR-291b-3p in glucose metabolism and its underlying mechanisms remain unknown. In the present study, we demonstrated that miR-291b-3p was abundantly expressed in the liver. Of note, hepatic miR-291b-3p expression was upregulated in HFD-fed mice and induced by fasting in C57BL/6 J normal mice. Importantly, hepatic inhibition miR-291b-3p expression ameliorated hyperglycemia and insulin resistance in HFD-fed mice, whereas hepatic overexpression of miR-291b-3p led to hyperglycemia and insulin resistance in C57BL/6 J normal mice. Further study revealed that miR-291b-3p suppressed insulin-stimulated AKT/GSK signaling and increased the expression of gluconeogenic genes in hepatocytes. Moreover, we identified that p65, a subunit of nuclear factor-κB (NF-κB), is a target of miR-291b-3p by bioinformatics analysis and luciferase reporter assay. Silencing of p65 significantly augmented the expression of PTEN and impaired AKT activation. In conclusion, we found novel evidence suggesting that hepatic miR-291b-3p mediated glycogen synthesis and gluconeogenesis through targeting p65 to regulate PTEN expression. Our findings indicate the therapeutic potential of miR-291b-3p inhibitor in hyperglycemia and insulin resistance.
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of physiology and pathophysiology, key laboratory of molecular cardiovascular science of the ministry of education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of physiology and pathophysiology, key laboratory of molecular cardiovascular science of the ministry of education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Yang
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fang
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yang
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Huang
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of physiology and pathophysiology, key laboratory of molecular cardiovascular science of the ministry of education, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Yang
authors.affiliation: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, 100730, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008112:Liver Glycogen; C000628700:MIRN291b microRNA, mouse; D035683:MicroRNAs; D051996:Transcription Factor RelA; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D005947:Glucose