内质网应激下miR-3648的上调及其在细胞增殖中的调控作用

发布时间：2018-08-05 18:39

【摘要】：miRNA是一类小非编码RNA,它们可以调控靶mRNA的稳定性和/或mRNA靶标翻译潜能。miRNA能相应地对细胞环境产生应答,并可促进细胞的生长或死亡。miRNA在包括内质网应激的多种细胞状态下发挥重要作用。我们发现一个人特异的miRNA miR-3648在内质网应激条件下被诱导。我们同时也发现miRNA-3648在转录水平上调。更进一步,我们用Luciferase实验证实了 miR-3648的一个靶标。在13个预测的靶标中,作为肿瘤抑制因子和Wnt/β catenin信号通路负调节因子的APC2被发现是miR-3648的直接靶标。当细胞在内质网应激或者在miR-3648过量表达条件下,APC2水平下调。用antagomir抑制miR-3648后,APC2水平升高、细胞增殖减慢。相反地,miR-3648过量表达使得APC2水平降低、细胞增殖加快。这个课题将内质网应激和Wnt/βcatenin signaling信号通路建立了新的联系。我们数据显示,miR-3648在内质网应激下的转录水平被诱导,通过下调APC2水平,加快细胞增殖
[Abstract]:MiRNA is a class of small noncoding RNA, which can regulate the stability of the target mRNA and / or the mRNA target translation potential.MiRNA can respond to the cell environment accordingly, and can promote cell growth or death of.MiRNA to play an important role in a variety of cell states including endoplasmic reticulum stress. We find a human specific miRNA miR-3648 in The endoplasmic reticulum was induced under stress conditions. We also found that miRNA-3648 was up-regulated at the transcriptional level. Further, we confirmed a target for miR-3648 in the Luciferase experiment. In the 13 predicted targets, APC2 as a tumor suppressor and a negative regulator of the Wnt/ beta catenin signaling pathway was found to be the direct target of miR-3648. When the cells were stressed in endoplasmic reticulum or under the overexpression of miR-3648, the level of APC2 was downregulated. After the suppression of miR-3648 with antagomir, the level of APC2 increased and the proliferation of cells slowed. On the contrary, the excessive expression of miR-3648 made the APC2 level decrease and the cell proliferation accelerated. This subject established the endoplasmic reticulum stress and the Wnt/ beta catenin signaling signaling pathway. New link. Our data show that microRNA3648 is induced at the transcriptional level under ER stress, accelerating cell proliferation by lowering APC2 levels.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：Q78

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