MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-κB signaling
MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-κB signaling
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DOI：
10.1152/ajpgi.00338.2009
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发表时间：
2010-04-01
影响因子：
4.5
通讯作者：
McCaffrey, Anton P.
中科院分区：
文献类型：
--
作者：
Marquez, Rebecca T.;Wendlandt, Erik;McCaffrey, Anton P.
Marquez RT、Wendlandt E、Galle CS、Keck K、McCaffrey AP。MicroRNA-21在肝再生的增殖期上调，靶向Pellino-1，并抑制NK-κ B信号传导。美国生理学杂志胃肠和肝脏生理学298：G535-G541，2010年。首次发表于2010年2月18日; doi：10.1152/ajpgi.00338.2009。在肝再生过程中，正常静止的肝细胞重新进入细胞周期，非实质细胞和实质细胞分裂，并恢复正常的肝结构。调控这些转变的基因表达程序尚未完全了解。MicroRNA是一类新发现的小分子调控RNA，通过与信使RNA的3 '-非翻译区（UTR）结合来沉默信使RNA。许多microRNA，包括miR-21，已被证明参与细胞增殖的调节。我们对小鼠进行了部分肝切除术，并允许肝脏再生1，6，12，24和48小时以及4和7天。我们通过北方印迹法比较了miR-21在肝切除术后肝脏和肝切除术前肝脏中的表达，发现miR-21在肝再生的早期阶段上调。NF-κ B信号传导也在肝再生过程中非常早地被激活。先前已报道NF-κ B上调miR-21前体转录物。预测的miR-21靶点Pellino（Peli 1）是一种参与激活NF-κ B信号传导的泛素连接酶。我们观察到在肝再生过程中miR-21和Peli 1 mRNA水平之间呈负相关。培养细胞中的miR-21过表达抑制Peli 1 3 '-UTR荧光素酶报告基因。使用NF-κ B报告基因分析，我们确定miR-21过表达抑制NF-κ B信号传导。总之，miR-21表达在肝再生的早期阶段上调。miR-21靶向Peli 1可能为调节NF-κ B信号传导的负反馈循环提供基础。
Marquez RT, Wendlandt E, Galle CS, Keck K, McCaffrey AP. MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NK-kappa B signaling. Am J Physiol Gastrointest Liver Physiol 298: G535-G541, 2010. First published February 18, 2010; doi:10.1152/ajpgi.00338.2009.- During liver regeneration, normally quiescent liver cells reenter the cell cycle, nonparenchymal and parenchymal cells divide, and proper liver architecture is restored. The gene expression programs regulating these transitions are not completely understood. MicroRNAs are a newly discovered class of small regulatory RNAs that silence messenger RNAs by binding to their 3'-untranslated regions ( UTRs). A number of microRNAs, including miR-21, have been shown to be involved in regulation of cell proliferation. We performed partial hepatectomies on mice and allowed the liver to regenerate for 1, 6, 12, 24, and 48 h and 4 and 7 days. We compared the expression of miR-21 in the posthepatectomy liver to the prehepatectomy liver by Northern blot and found that miR-21 was upregulated during the early stages of liver regeneration. NF-kappa B signaling is also activated very early during liver regeneration. It has been previously reported that NF-kappa B upregulates the miR-21 precursor transcript. The predicted miR-21 target, Pellino (Peli1), is a ubiquitin ligase involved in activating NF-kappa B signaling. We observed an inverse correlation between miR-21 and Peli1 mRNA levels during liver regeneration. miR-21 overexpression in cultured cells inhibited a Peli1 3'-UTR luciferase reporter. Using NF-kappa B reporter assays, we determined that miR-21 overexpression inhibits NF-kappa B signaling. In conclusion, miR-21 expression was upregulated during early stages of liver regeneration. Targeting of Peli1 by miR-21 could potentially provide the basis for a negative feedback cycle regulating NF-kappa B signaling.