AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Gu, D. | - |
dc.contributor.author | Ahn, S.H. | - |
dc.contributor.author | Eom, S. | - |
dc.contributor.author | Lee, H.-S. | - |
dc.contributor.author | Ham, J. | - |
dc.contributor.author | Lee, D.H. | - |
dc.contributor.author | Cho, Y.K. | - |
dc.contributor.author | Koh, Y. | - |
dc.contributor.author | Ignatova, E. | - |
dc.contributor.author | Jang, E.-S. | - |
dc.contributor.author | Chi, S.W. | - |
dc.date.accessioned | 2021-08-30T02:19:55Z | - |
dc.date.available | 2021-08-30T02:19:55Z | - |
dc.date.created | 2021-06-17 | - |
dc.date.issued | 2021-03-05 | - |
dc.identifier.issn | 2162-2531 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/49401 | - |
dc.description.abstract | Small interfering RNAs (siRNAs) therapeutically induce RNA interference (RNAi) of disease-causing genes, but they also silence hundreds of seed-matched off-targets as behaving similar to microRNAs (miRNAs). miRNAs control the pathophysiology of tumors, wherein their accessible binding sites can be sequenced by Argonaute crosslinking immunoprecipitation (AGO CLIP). Herein, based on AGO CLIP, we develop potent anticancer siRNAs utilizing miRNA-like activity (mi/siRNAs). The mi/siRNAs contain seed sequences (positions 2–7) of tumor-suppressive miRNAs while maintaining perfect sequence complementarity to the AGO-accessible tumor target sites. Initially, host miRNA interactions with human papillomavirus 18 (HPV18) were identified in cervical cancer by AGO CLIP, revealing tumor-suppressive activity of miR-1/206 and miR-218. Based on the AGO-miRNA binding sites, mi/siRNAs were designed to target E6 and E7 (E6/E7) transcript with seed sequences of miR-1/206 (206/E7) and miR-218 (218/E7). Synergistic anticancer activity of 206/E7 and 218/E7 was functionally validated and confirmed via RNA sequencing and in vivo xenograft models (206/E7). Other mi/siRNA sequences were additionally designed for cervical, ovarian, and breast cancer, and available as an online tool (http://ago.korea.ac.kr/misiRNA); some of the mi/siRNAs were validated for their augmented anticancer activity (206/EphA2 and 206/Her2). mi/siRNAs could coordinate miRNA-like activity with robust siRNA function, demonstrating the potential of AGO CLIP analysis for RNAi therapeutics. © 2021 The AuthorsThe gene silencing activity of siRNAs depends on target accessibility of Argonaute (AGO) and has a problem to induce miRNA-like repression of seed-matched off-targets. Based on AGO CLIP sequencing analyses, Gu and colleagues developed a robust strategy to design anticancer siRNAs (mi/siRNAs), which utilize AGO-accessible tumor target sites to augment tumor-suppressive miRNA-like activity. © 2021 The Authors | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | Cell Press | - |
dc.title | AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Eom, S. | - |
dc.contributor.affiliatedAuthor | Chi, S.W. | - |
dc.identifier.doi | 10.1016/j.omtn.2021.01.018 | - |
dc.identifier.scopusid | 2-s2.0-85101039613 | - |
dc.identifier.wosid | 000631858600010 | - |
dc.identifier.bibliographicCitation | Molecular Therapy - Nucleic Acids, v.23, pp.1172 - 1190 | - |
dc.relation.isPartOf | Molecular Therapy - Nucleic Acids | - |
dc.citation.title | Molecular Therapy - Nucleic Acids | - |
dc.citation.volume | 23 | - |
dc.citation.startPage | 1172 | - |
dc.citation.endPage | 1190 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR | - |
dc.subject.keywordPlus | HUMAN-PAPILLOMAVIRUS | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | CONTRIBUTES | - |
dc.subject.keywordPlus | MICRORNAS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | CARCINOMA | - |
dc.subject.keywordPlus | INSIGHTS | - |
dc.subject.keywordAuthor | AGO CLIP | - |
dc.subject.keywordAuthor | breast cancer | - |
dc.subject.keywordAuthor | cervical cancer | - |
dc.subject.keywordAuthor | miRNA | - |
dc.subject.keywordAuthor | ovarian cancer | - |
dc.subject.keywordAuthor | siRNA | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.