Abstract
Abstract Heparanase (HPSE) is the only known enzyme that cleaves the polymeric heparan sulfate (HS), a key component of the extracellular matrix (ECM). Heparanase has been implicated in various pathophysiological conditions involving ECM remodeling, such as tumor progression, metastasis angiogenesis, and inflammation. To study the role of heparanase in diseases, we developed a strategy to epigenetically modulate its expression in cells based on the clustered regularly interspaced short palindromic repeats (CRISPR) system. A fusion protein of dCAS9 can be directed to the HPSE gene via one or a combination of single guide RNAs. By linking dCas9 with different histone modification enzymes (eg. P300, hHDAC3, LSD1), the expression of heparanase can be up- or down-regulated through histone acetylation, deacetylation and demethylation. This approach allows us to tune heparanase expression in various cell lines on demand, enabling the study of heparanase activity in real-time. This work will also lead to novel therapeutics targeting heparanase. Citation Format: Zixin Chen, Guihua Zeng, Xiaogang Li, Fu-Sen Liang, Lina Cui. Epigenetic control of heparanase expression using CRISPR/dCas9 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2112.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
