标题：CREB-upregulated lncRNA MEG3 promotes hepatic gluconeogenesis by regulating miR-302a-3p-CRTC2 axis
作者：Zhu, Xiang; Li, Hongqi; Wu, Yuanbo; Zhou, Jian; Yang, Guangwei; Wang, Weidong; Kang, Dongmei; Ye, Shandong
作者机构：[Zhu, Xiang] Shandong Univ, Sch Med, Jinan, Shandong, Peoples R China.; [Zhu, Xiang; Li, Hongqi; Zhou, Jian; Wang, Weidong; Kang, Dongmei] Univ Sci 更多
通讯作者地址：[Ye, SD]Univ Sci & Technol China, Div Life Sci & Med, Affiliated Hosp 1, Dept Endocrinol, 17 Lujiang Rd, Hefei 230001, Anhui, Peoples R China.
来源：JOURNAL OF CELLULAR BIOCHEMISTRY
关键词：CRTC2; hepatic gluconeogenesis; MEG3; miR-302a-3p
摘要：Hepatic gluconeogenesis is the major contributor to hyperglycemia in diabetes. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been shown to promote hepatic insulin resistance; however, the underlying mechanism involving hepatic gluconeogenesis remains unclear. This study aims to investigate the potential role of MEG3 in hepatic gluconeogenesis. Mouse primary hepatocytes were used in this study. Cell transfection was performed for the overexpression or knockdown of specific genes. Expressions of MEG3, miR-302a-3p, CREB-regulated transcriptional coactivator 2 (CRTC2), protein kinase A (PKA), cAMP-response element binding protein (CREB), PPAR gamma coactivator-1 alpha (PGC-1 alpha), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pc) were determined by quantitative real-time polymerase chain reaction (qRT-qPCR) and Western blot analysis, respectively. The association among MEG3, miR-302a-3p, and CRTC2 was disclosed by dual-luciferase reporter assay. MEG3 was highly expressed in high glucagon-treated mouse primary hepatocytes. CREB-induced MEG3 upregulation increased gluconeogenic gene expression in high glucagon-treated primary hepatocytes, while MEG3 interference led to an opposite effect. MEG3 served as a competing endogenous RNA (ceRNA) to upregulate CRTC2 by targeting miR-302a-3p in primary hepatocytes, thereby increasing PGC-1 alpha-PEPCK/G6Pc. CREB-upregulated MEG3-enhanced hepatic gluconeogenesis via mediating miR-302a-3p-CRTC2 axis, revealing that MEG3 might be a potential target and therapeutic strategy for diabetes.