MiR-709 inhibits GHRP6 induced GH synthesis by targeting PRKCA in pituitary. (15th April 2020)

• Record Type: Journal Article
• Authors: Cheng, Yunyun; Chen, Ting; Song, Jie; Qi, Qien; Wang, Chunli; Xi, Qianyun; Liu, Songcai; Hao, Linlin; Zhang, Yongliang
• Is Part Of: Molecular and cellular endocrinology. Volume 506(2020)
• Publication Date: 2020-04-15
• Subjects: Pituitary -- GH -- miR-709 -- PKCα -- GHRP6; GH growth hormone -- miRNA microRNA -- PRKCA protein kinase C alpha -- cAMP Cyclic Adenosine monophosphate -- CREB cAMP response element binding protein -- ERK extracellular regulated kinase -- PKA protein kinase A -- GC guanylate cyclase -- GHRP6 growth hormone releasing peptide 6 -- GHRH growth hormone releasing hormone -- SS somatostatin -- GPCR G protein coupling receptor -- LH luteinizing hormone -- MFE minimum free energy -- PCR polymerase chain reaction -- qRT-PCR quantificational real-time polymerase chain reaction -- 3′UTR 3′ untranslated regions -- ELISA enzyme-linked immunosorbent assay; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2020.110763
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Pituitary growth hormone (GH) plays an essential role in processes of organism growth and metabolism. MicroRNA (miRNA) could also participate in diverse biological processes. However, the role of miRNA in the regulation of pituitary GH during the growth process remains unclear. In this study, we firstly confirmed that the second highly expressed pituitary miRNA (miR-709) significantly inhibited the GH synthesis and suppressed the viability of GH3 cells. The bioinformatics analysis and dual luciferase report system were used to ascertain the PRKCA is the direct target gene of miR-709, which is the coding gene of PKCα. Then the transcription and translation levels of Prkca were obvious reduced by the over-expression of miR-709 in GH3 cells, followed by the inhibition of the transcription factor (CREB1) of Gh1 gene and the ERK1/2 signaling pathway or the possible cross-talk signaling pathway (cAMP/PKA signaling pathway) detected by western blot, suggesting that ERK1/2 maybe an important factor involved in the GH3 cell viability mediated by PKCα. At last, GHRP6 increased PKCα and GH expression but reduced miR-709 expression in vitro and vivo assays, and this conclusion was further confirmed by the result of GHRP6 attenuated the inhibition of miR-709 on GH expression. These findings will provide new molecular mechanism on the regulation of pituitary GH. Graphical abstract: Image 1 Highlights: miR-709 is highly expressed in the rat pituitary gland and GH3 cells. miR-709 inhibits the proliferation of GH3 cells and synthesis of GH. PRKCA is the direct target gene of miR-709 and miR-709 downregulates the expression of PKCα. miR-709 inhibits GH by mediating ERK1/2 signaling pathway and PKA/CREB signaling pathway downstream of PKCα. GHRP6 reduces miR-709 expression and attenuates the inhibition of miR-709 on GH expression.