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在白鱼体内递送 microRNA:合成的 MiR92b-3p 摄取及其基因表达沉默的功效。

In vivo miRNA delivery in whitefish: Synthetic MiR92b-3p uptake and the efficacy of gene expression silencing.

机构信息

1 Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn 10-709, Poland.

2 Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn 10-713, Poland.

出版信息

Exp Biol Med (Maywood). 2019 Jan;244(1):52-63. doi: 10.1177/1535370218824573. Epub 2019 Jan 21.

DOI:10.1177/1535370218824573
PMID:30664358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6362533/
Abstract

The delivery of short snippets of RNA, such as synthetic miRNA agents, is an essential step for achieving RNA-mediated knockdown, which has not been studied in sufficient detail in fish. Our results indicate that a MiR92b-3p mimic may be effectively delivered via intraperitoneal injection to the spleen and the liver of whitefish, and that it likely achieves functionality without causing any apparent toxic effects in the challenged animals. We report the novel finding that the MiR92b-3p mimic reduced the in vivo liver mRNA expression levels of its putative pro-apoptotic targets (p53, cdkn1a, and pcna), and important metabolic genes, e.g. cdo1. This shows that this methodology of MiR92b-3p mimic transfection in vivo may be a useful tool for studies that investigate the molecular pathways that confer pro-proliferative and anti-apoptotic phenotypes or those that regulate intracellular metabolism in fish and other vertebrates.

摘要

短片段 RNA(如合成 miRNA 试剂)的递呈是实现 RNA 介导的基因敲低的关键步骤,但在鱼类中尚未对此进行充分研究。我们的结果表明,miR92b-3p 模拟物可通过腹腔注射有效递送至白鲑的脾脏和肝脏,并且在接受挑战的动物中可能不会产生任何明显的毒性作用而发挥功能。我们报告了一个新发现,即 miR92b-3p 模拟物降低了体内肝脏 mRNA 表达水平其潜在的促凋亡靶标(p53、cdkn1a 和 pcna)和重要的代谢基因,例如 cdo1。这表明,这种体内 miR92b-3p 模拟物转染的方法可能是研究赋予促增殖和抗凋亡表型或调节鱼类和其他脊椎动物细胞内代谢的分子途径的有用工具。

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本文引用的文献

1
Microcystin-LR-Triggered Neuronal Toxicity in Whitefish Does Not Involve MiR124-3p.微囊藻毒素-LR 诱导白鲑神经元毒性不涉及 miR124-3p。
Neurotox Res. 2019 Jan;35(1):29-40. doi: 10.1007/s12640-018-9920-4. Epub 2018 Jun 7.
2
miRNA-8159 is involved in TLR signaling pathway regulation after pathogen infection by direct targeting TLR13 in miiuy croaker.miRNA-8159 通过直接靶向米鱼 TLR13 参与病原体感染后的 TLR 信号通路调节。
Fish Shellfish Immunol. 2017 Jul;66:531-539. doi: 10.1016/j.fsi.2017.05.046. Epub 2017 May 22.
3
Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures.将白鱼腹腔暴露于微囊藻毒素-LR会导致肝脏迅速受损,随后再生并对后续暴露产生耐受性。
Toxicol Appl Pharmacol. 2016 Dec 15;313:68-87. doi: 10.1016/j.taap.2016.10.014. Epub 2016 Oct 17.
4
Illumina Sequencing Reveals Aberrant Expression of MicroRNAs and Their Variants in Whitefish (Coregonus lavaretus) Liver after Exposure to Microcystin-LR.Illumina测序揭示了暴露于微囊藻毒素-LR后白鲑(Coregonus lavaretus)肝脏中微小RNA及其变体的异常表达。
PLoS One. 2016 Jul 8;11(7):e0158899. doi: 10.1371/journal.pone.0158899. eCollection 2016.
5
Gene evolution and gene expression after whole genome duplication in fish: the PhyloFish database.鱼类全基因组复制后的基因进化与基因表达:PhyloFish数据库
BMC Genomics. 2016 May 18;17:368. doi: 10.1186/s12864-016-2709-z.
6
MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST.微小RNA-92b通过靶向Smad7促进肝细胞癌进展,并由长链非编码RNA XIST介导。
Cell Death Dis. 2016 Apr 21;7(4):e2203. doi: 10.1038/cddis.2016.100.
7
MiR-21 is required for efficient kidney regeneration in fish.MiR-21是鱼类高效肾脏再生所必需的。
BMC Dev Biol. 2015 Nov 17;15:43. doi: 10.1186/s12861-015-0089-2.
8
Emerging Role of microRNA in Neuropathic Pain.微小RNA在神经性疼痛中的新作用
Curr Drug Metab. 2016;17(4):336-44. doi: 10.2174/1389200216666151015113400.
9
siRNA Versus miRNA as Therapeutics for Gene Silencing.作为基因沉默疗法的小干扰RNA与微小RNA
Mol Ther Nucleic Acids. 2015 Sep 15;4(9):e252. doi: 10.1038/mtna.2015.23.
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miR-122-5p as a plasma biomarker of liver injury in fish exposed to microcystin-LR.miR-122-5p作为暴露于微囊藻毒素-LR的鱼类肝脏损伤的血浆生物标志物。
J Fish Dis. 2016 Jun;39(6):741-51. doi: 10.1111/jfd.12406. Epub 2015 Sep 8.