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核糖体蛋白 L29 对肺和脑中 miR22 表达的组织特异性调节。

The tissue specific regulation of miR22 expression in the lung and brain by ribosomal protein L29.

机构信息

Department of Biochemistry and Molecular Biology, School of Medical Laboratory, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, 2600 Donghai Street, Bengbu, 233030, Anhui, People's Republic of China.

Department of Basic Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.

出版信息

Sci Rep. 2020 Oct 1;10(1):16242. doi: 10.1038/s41598-020-73281-z.

DOI:10.1038/s41598-020-73281-z
PMID:33004906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7530758/
Abstract

Endogenous miR22 is associated with a diverse range of biological processes through post-translational modification of gene expression and its deregulation results in various diseases including cancer. Its expression is usually tissue or cell-specific, however, the reasons behind this tissue or cell specificity are not clearly outlined till-date. Therefore, our keen interest was to investigate the mechanisms of tissue or cell-specific expression of miR22. In the current study, miR22 expression showed a tissues-specific difference in the poly(I:C) induced inflammatory mouse lung and brain tissues. The cell-specific different expression of miR22 was also observed in inflammatory glial cells and endothelial cells. The pattern of RPL29 expression was also similar to miR22 in these tissues and cells under the same treatment. Interestingly, the knockdown of RPL29 exerted an inhibitory effect on miR22 and its known transcription factors including Fos-B and c-Fos. Fos-B and c-Fos were also differentially expressed in the two cell lines transfected with poly(I:C). The knockdown of c-Fos also exerted its negative effects on miR22 expression in both cells. These findings suggest that RPL29 might have regulatory roles on tissue or cell-specific expression of miR22 through the transcription activities of c-Fos and also possibly through Fos-B.

摘要

内源性 miR22 通过基因表达的翻译后修饰与多种生物过程相关,其失调导致包括癌症在内的各种疾病。它的表达通常是组织或细胞特异性的,然而,到目前为止,这种组织或细胞特异性的背后原因还没有明确的概述。因此,我们非常感兴趣的是研究 miR22 组织或细胞特异性表达的机制。在本研究中,miR22 在 poly(I:C)诱导的炎症性小鼠肺和脑组织中表现出组织特异性差异。在炎症性神经胶质细胞和内皮细胞中也观察到 miR22 的细胞特异性差异表达。在相同的处理下,RPL29 的表达模式与 miR22 也相似。有趣的是,RPL29 的敲低对 miR22 及其已知的转录因子(包括 Fos-B 和 c-Fos)产生了抑制作用。在转染 poly(I:C)的两种细胞系中,Fos-B 和 c-Fos 的表达也存在差异。c-Fos 的敲低也对两种细胞中的 miR22 表达产生了负面影响。这些发现表明,RPL29 可能通过 c-Fos 的转录活性以及可能通过 Fos-B 对 miR22 的组织或细胞特异性表达具有调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/9fcada08c6f4/41598_2020_73281_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/b67a96e9be32/41598_2020_73281_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/8b961b525a43/41598_2020_73281_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/ce5f67863e8e/41598_2020_73281_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/3411b018818f/41598_2020_73281_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/9fcada08c6f4/41598_2020_73281_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/b67a96e9be32/41598_2020_73281_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/8b961b525a43/41598_2020_73281_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/ce5f67863e8e/41598_2020_73281_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/3411b018818f/41598_2020_73281_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/900c/7530758/9fcada08c6f4/41598_2020_73281_Fig5_HTML.jpg

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c-Fos-dependent miR-22 targets MDC1 and regulates DNA repair in terminally differentiated cells.
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