Identification of microRNA transcriptome reveals that miR-100 is involved in the renewal of porcine intestinal epithelial cells  

作　　者：Lijun Zou Xia Xiong Huansheng Yang Kexing Wang Jian Zhou Dinghong Lv Yulong Yin 

机构地区：[1]Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, School of Life Sciences, Hunan Normal University, Changsha 410081, China [2]Key Laboratory for Agro-Ecological Processes in Subtropical Regions, Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Changsha 410125, China [3]Laboratory of Basic Biology, Hunan First Normal University, Changsha 410205, China

出　　处：《Science China(Life Sciences)》2019年第6期816-828,共13页中国科学（生命科学英文版）

基　　金：supported by the Key Programs of Frontier Scientific Research of the Chinese Academy of Sciences (QYZDYSSW-SMC008);National Program on Key Basic Research Project (2016YFD0500504);National Nature Science Foundation of China (31330075; 31572420);Hunan Provincial Natural Science Foundation of China (2018JJ3094; 2018JJ1028);Research Foundation of Education Bureau of Hunan Province, China (18B476);Hunan Provincial Innovation Foundation for Postgraduate (CX2016B172)

摘　　要：MicroRNAs play important roles in various cellular processes, including differentiation, proliferation and survival. Using a pig model, this study sought to identify the miRNAs responsible for crypt-villus axis renewal of the small intestinal epithelium.Compared to the villus upper cells, there were 15 up-regulated and 41 down-regulated miRNAs in the crypt cells of the jejunum.Notably, we found that miR-100 was expressed more in the villus upper cells than in the crypt cells, suggesting an effect on intestinal epithelium differentiation. Overexpression of miR-100 increased the activity of alkaline phosphatase, confirming that miR-100 promoted IPEC-J2 cell differentiation. MiR-100 can inhibit cell proliferation as evidenced by CCK-8 and cell cycle assay results. We also showed that miR-100 significantly inhibited the migration of IPEC-J2 cells and promoted cell apoptosis through caspase-3-dependent cleavage of Bcl-2. Furthermore, FGFR3 was identified as a potential target of miR-100 by bioinformatics analysis. We confirmed that overexpression of miR-100 suppressed FGFR3 expression in IPEC-J2 cells by directly targeting the FGFR3 3′-UTR. This is the first report of miRNAs acting on the renewal of the intestinal crypt-villus axis.Our results also showed that miR-100 promotes the differentiation and apoptosis, and inhibits the proliferation and migration of enterocytes of pigs.MicroRNAs play important roles in various cellular processes, including differentiation, proliferation and survival. Using a pig model, this study sought to identify the miRNAs responsible for crypt-villus axis renewal of the small intestinal epithelium.Compared to the villus upper cells, there were 15 up-regulated and 41 down-regulated miRNAs in the crypt cells of the jejunum.Notably, we found that miR-100 was expressed more in the villus upper cells than in the crypt cells, suggesting an effect on intestinal epithelium differentiation. Overexpression of miR-100 increased the activity of alkaline phosphatase, confirming that miR-100 promoted IPEC-J2 cell differentiation. MiR-100 can inhibit cell proliferation as evidenced by CCK-8 and cell cycle assay results. We also showed that miR-100 significantly inhibited the migration of IPEC-J2 cells and promoted cell apoptosis through caspase-3-dependent cleavage of Bcl-2. Furthermore, FGFR3 was identified as a potential target of miR-100 by bioinformatics analysis. We confirmed that overexpression of miR-100 suppressed FGFR3 expression in IPEC-J2 cells by directly targeting the FGFR3 3′-UTR. This is the first report of miRNAs acting on the renewal of the intestinal crypt-villus axis.Our results also showed that miR-100 promotes the differentiation and apoptosis, and inhibits the proliferation and migration of enterocytes of pigs.

关 键 词：MicroRNAs SUCKLING PIGLETS crypt-villus axis cell RENEWAL IPEC-J2 cells 

分 类 号：Q[生物学]