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通过噬菌体展示筛选肽对miR-21进行选择性抑制。

Selective inhibition of miR-21 by phage display screened peptide.

作者信息

Bose Debojit, Nahar Smita, Rai Manish Kumar, Ray Arjun, Chakraborty Kausik, Maiti Souvik

机构信息

Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India.

Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR. Mathura Road, Delhi 110020, India Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi-110001, India.

出版信息

Nucleic Acids Res. 2015 Apr 30;43(8):4342-52. doi: 10.1093/nar/gkv185. Epub 2015 Mar 30.

DOI:10.1093/nar/gkv185
PMID:25824952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4417150/
Abstract

miRNAs are nodal regulators of gene expression and deregulation of miRNAs is causally associated with different diseases, including cancer. Modulation of miRNA expression is thus of therapeutic importance. Small molecules are currently being explored for their potential to downregulate miRNAs. Peptides have shown to have better potency and selectivity toward their targets but their potential in targeting and modulating miRNAs remain unexplored. Herein, using phage display we found a very selective peptide against pre-miR-21. Interestingly, the peptide has the potential to downregulate miR-21, by binding to pre-miR-21 and hindering Dicer processing. It is selective towards miR-21 inside the cell. By antagonising miR-21 function, the peptide is able to increase the expression of its target proteins and thereby increase apoptosis and suppress cell proliferation, invasion and migration. This peptide can further be explored for its anti-cancer activity in vivo and may be even extended to clinical studies.

摘要

微小RNA（miRNA）是基因表达的关键调节因子，miRNA的失调与包括癌症在内的多种疾病存在因果关联。因此，调节miRNA表达具有重要的治疗意义。目前正在探索小分子下调miRNA的潜力。肽类对其靶标显示出更好的效力和选择性，但其在靶向和调节miRNA方面的潜力仍未得到探索。在此，我们利用噬菌体展示技术发现了一种针对前体miR-21的高选择性肽。有趣的是，该肽通过与前体miR-21结合并阻碍Dicer加工，具有下调miR-21的潜力。它在细胞内对miR-21具有选择性。通过拮抗miR-21的功能，该肽能够增加其靶蛋白的表达，从而增加细胞凋亡并抑制细胞增殖、侵袭和迁移。这种肽可进一步探索其体内抗癌活性，甚至可能扩展到临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/06417e3cf18c/gkv185fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/3a5d21771cc2/gkv185fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/4aa87a572fe8/gkv185fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/ec6eadb9ab33/gkv185fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/73ca44f474f8/gkv185fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/eb009c131b7d/gkv185fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/db0a580b888c/gkv185fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/06417e3cf18c/gkv185fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/3a5d21771cc2/gkv185fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/4aa87a572fe8/gkv185fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/ec6eadb9ab33/gkv185fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/73ca44f474f8/gkv185fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/eb009c131b7d/gkv185fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/db0a580b888c/gkv185fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8037/4417150/06417e3cf18c/gkv185fig7.jpg

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Bioinformatics. 2014 Jun 15;30(12):1771-3. doi: 10.1093/bioinformatics/btu097. Epub 2014 Feb 14.
2
Sequence-based design of bioactive small molecules that target precursor microRNAs.基于序列设计针对前体 microRNA 的生物活性小分子。
Nat Chem Biol. 2014 Apr;10(4):291-7. doi: 10.1038/nchembio.1452. Epub 2014 Feb 9.
3
Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor.
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ACS Chem Biol. 2023 Feb 17;18(2):237-250. doi: 10.1021/acschembio.2c00502. Epub 2023 Feb 2.
4
Structure of pre-miR-31 reveals an active role in Dicer processing.前体微小RNA-31的结构揭示了其在Dicer加工过程中的积极作用。
bioRxiv. 2023 Jan 3:2023.01.03.519659. doi: 10.1101/2023.01.03.519659.
5
3D Modeling of Non-coding RNA Interactions.非编码RNA相互作用的三维建模
Adv Exp Med Biol. 2022;1385:281-317. doi: 10.1007/978-3-031-08356-3_11.
6
Discovery of a novel small molecular peptide that disrupts helix 34 of bacterial ribosomal RNA.发现一种破坏细菌核糖体RNA螺旋34的新型小分子肽。
RSC Adv. 2019 Dec 4;9(69):40268-40276. doi: 10.1039/c9ra07812f. eCollection 2019 Dec 3.
7
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8
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