MiR-139 suppresses β-casein synthesis and proliferation in bovine mammary epithelial cells by targeting the GHR and IGF1R signaling pathways

BMC Veterinary Research

Research Article

Jinxia Ao¹  Xia Sun²  Qingzhang Li²  Xuejun Gao²  Chunmei Wang²  Lianfeng Jin²  Guangpu Yu²  Yingjun Cui³ 

[1] College of Life Science, Northeast Agricultural University, 150030, Harbin, Heilongjiang, People’s Republic of China;Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University, 150030, Harbin, Heilongjiang, People’s Republic of China;Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University, 150030, Harbin, Heilongjiang, People’s Republic of China;College of Life Science, Northeast Agricultural University, 150030, Harbin, Heilongjiang, People’s Republic of China;

关键词: miR-139;    Mammary gland;    β-casein;    Growth hormone receptor;    Type I insulin-like growth factor receptor;   

DOI  :  10.1186/s12917-017-1267-1

 received in 2016-07-12, accepted in 2017-11-09,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMicroRNAs have important roles in many biological processes. However, the role of miR-139 in healthy mammary gland remains unclear. The objective of this study was to investigate the effects of miR-139 on lactation in dairy cows.ResultsHere, we found that miR-139 was down-regulated in mid-lactation dairy cow mammary tissues compared with mid-pregnancy tissues. Then, we prioritized two of potential target genes of miR-139 in cow, growth hormone receptor (GHR) and type I insulin-like growth factor receptor (IGF1R) for further functional studies based on their roles in lactation processes. Dual luciferase reporter assays validated direct binding of miR-139 to the 3′- untranslated region (UTR) of GHR and IGF1R. Moreover, over-expression or silencing of miR-139 affected mRNA levels of GHR and IGF1R in cultured bovine mammary epithelial cells (BMECs). Furthermore, over-expression of miR-139 decreased protein levels of β-casein, proliferation in mammary epithelial cell, and the protein levels of IGF1R and key members of the GHR or IGF1R pathways as well, whereas silencing miR-139 produced the opposite result. Among these signal molecules, signal transducer and activator of transcription-5 (STAT5), protein kinase B (also known as AKT1), mammalian target of rapamycin (mTOR), and p70-S6 Kinase (p70S6K) are involed in β-casein synthesis, and Cyclin D1 is involved in cell proliferation. In addition, silencing GHR decreased protein levels of β-casein, IGF1R, and key members of the IGF1R pathway, whereas co-silencing miR-139 and GHR rescued the expression of GHR and reversed GHR silencing effects.ConclusionsOur results demonstrate that GHR and IGF1R are target genes of miR-139 in dairy cow. MiR-139 suppresses β-casein synthesis and proliferation in BMECs by targeting the GHR and IGF1R signaling pathways.

【 授权许可】

CC BY   
© The Author(s). 2017