Wang Yanli, Lv Ke, Zhao Mei, Chen Hailong, Ji Guohua, Zhang Yongliang, Wang Tingmei, Cao Hongqing, Li Yinghui, Qu Lina
School of Life Sciences, Northwestern Polytechnical University, Xian, Shaanxi, China.
State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
PeerJ. 2019 Nov 28;7:e8119. doi: 10.7717/peerj.8119. eCollection 2019.
The circadian clock controls the physiological functions of many tissues including the liver via an autoregulatory transcriptional-translational feedback loop, of which CLOCK is a core positive component. In addition, many studies have indicated that microRNAs (miRNAs) regulate liver function. However, how CLOCK-regulated miRNAs are linked to liver function remains largely unknown. In this study, miRNAs expression profiles were performed in the liver of mutant mice. Compared to wild type mice, totals of 61 and 57 putative CLOCK-regulated miRNAs were differentially expressed (fold change absolute value ≥2) at zeitgeber time 2 and zeitgeber time 14, respectively. According to the pathway analyses, the target genes of differentially expressed miRNAs were mainly involved in pathways in cancer, the PI3K-Akt signaling pathway and the MAPK signaling pathway. Protein-protein interaction analyses revealed that the hub genes were primarily associated with pathway in cancer and circadian rhythms. Expression validation showed that while the expression levels of miR-195 and miR-340 were up-regulated, the rhythms of these two miRNAs were always maintained. The expression level of nr1d2 mRNA was down-regulated. We identified a number of prospective CLOCK-regulated miRNAs that play roles in the various physiological processes of the liver, providing a reference to better understanding the potential regulatory mechanisms in the liver.
生物钟通过一个自动调节的转录-翻译反馈环控制包括肝脏在内的许多组织的生理功能，其中CLOCK是一个核心的正向组件。此外，许多研究表明，微小RNA（miRNA）调节肝功能。然而，CLOCK调节的miRNA如何与肝功能相关联在很大程度上仍然未知。在本研究中，对突变小鼠肝脏进行了miRNA表达谱分析。与野生型小鼠相比，在授时时间2和授时时间14时，分别有61个和57个推定的CLOCK调节的miRNA差异表达（倍数变化绝对值≥2）。根据通路分析，差异表达的miRNA的靶基因主要参与癌症通路、PI3K-Akt信号通路和MAPK信号通路。蛋白质-蛋白质相互作用分析表明，枢纽基因主要与癌症通路和昼夜节律相关。表达验证表明，虽然miR-195和miR-340的表达水平上调，但这两种miRNA的节律始终保持。nr1d2 mRNA的表达水平下调。我们鉴定了许多在肝脏各种生理过程中起作用的潜在CLOCK调节的miRNA，为更好地理解肝脏中的潜在调节机制提供了参考。
