CREB‐upregulated lncRNA MEG3 promotes hepatic gluconeogenesis by regulating miR‐302a‐3p‐CRTC2 axis. Issue 3 (27th September 2018)

• Record Type: Journal Article
• Authors: Zhu, Xiang; Li, Hongqi; Wu, Yuanbo; Zhou, Jian; Yang, Guangwei; Wang, Weidong; Kang, Dongmei; Ye, Shandong
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 3(2019)
• Page Start: 4192
• Page End: 4202
• Publication Date: 2018-09-27
• Subjects: CRTC2 -- hepatic gluconeogenesis -- MEG3 -- miR‐302a‐3p; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27706
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: 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), PPARγ coactivator‐1α (PGC‐1α), 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‐1α‐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. Abstract : The current study suggests that CREB‐mediated upregulation of lncRNA MEG3 can increase hepatic gluconeogenic genes PGC‐1α‐PEPCK/G6Pc pathway via regulating the miR‐302a‐3p target gene CRTC2, thereby providing a new insight into the molecular mechanism of hepatic gluconeogenesis and novel targets and strategies for the treatment of diabetes.